Medical Education Review Articles 51

M. Michael1 · B. Hossfeld2 · D. Häske3 · A. Bohn4 · M. Bernhard1 Analgesia, sedation and anaesthesia in emergency care

 Citation: Michael M, Hossfeld B, Häske D, Bohn A, Bernhard M: Analgesie, Sedierung und Anästhesie in der Notfallmedizin. Anästh Intensivmed 2020;61:051–063. DOI: 10.19224/ai2020.051

1 Zentrale Notaufnahme, Universitäts­ Summary during intubation (if required), airway klinikum Düsseldorf management and securing of the endo­ (Ärztlicher Leiter: Priv.-Doz. Dr. Sedation, analgesia and emergency tracheal tube following verification of M. Bernhard) anaesthesia are key elements of pre- correct placement. Standard preparation 2 Klinik für Anästhesiologie, Intensiv­ hospital emergency medical care. These medizin, Notfallmedizin und Schmerz- for general anaesthesia includes prior measures pose a significant challenge to therapie, Bundeswehrkrankenhaus Ulm accord, secure labelling of anaesthetic (Direktor: Prof. Dr. M. Helm) the whole emergency team. Pain may be and emergency drugs, checking required 3 Eberhard Karls Universität Tübingen / eased through supportive measures (e.g. equipment and making available alter­ DRK Rettungsdienst Reutlingen, Medizi- reduction of fractures, immobilisation) nische Fakultät native airway management devices. Stan­ and verbal emotional support. In many (Direktor: Prof. Dr. P. Rosenberger) dard monitoring for prehospital analge- 4 Stadt Münster, Feuerwehr, Ärztlicher cases however, patients will only be pain sia, sedation and emergency anaesthesia Leiter Rettungsdienst / Klinik für Anästhe- free once potent analgesics have been siologie, operative Intensivmedizin und should include an electrocardiogram, administered. Numerous emergency me-­ Schmerztherapie, Universitätsklinikum automatic or manual measurement of Münster dical services in Germany permit trained blood pressure and pulse oximetry. Con- (Direktor: Prof. Dr. A. Zarbock) and certified paramedics (“Notfallsani­ tinuous capnography is required without täter”) to administer analgesics and exception for verification of correct en- anal­gosedation in accordance with stan- dotracheal tube placement, for detection dard operating procedures within the of disconnection or dislocation and for scope of job delegation. Whilst this can indirect haemodynamic monitoring. shorten the time to treatment especially for severe pain, it does not make the emergency physician redundant. Basic Introduction monitoring should be established as a matter of principle whenever analgose- Analgesia, sedation and emergency dation is administered. Provision of anaesthesia are the cornerstones of emergency anaesthesia is reserved for prehospital emergency care. emergency physicians and includes a critical evaluation of the indication for anaesthesia, taking into account patient, Standards employed in a hospital en­vi­ron­- scenario and provider-related factors. ment cannot unreservedly be assigned As a rule, rapid sequence induction to emergency medical services (EMS). (RSI; aka “crash” induction) should be Numerous scenario and patient-specific used for emergency anaesthesia and features need to be taken into account, as should include the following points: do regional guidelines and the personal Keywords standard monitoring, preoxygenation, experience of the provider, all of which Sedation – Analgesia – Emer- standardised provisions for emergency play significant roles in the provision of gency Anaesthesia – Out-of- anaesthesia (anaesthetic and emergency emergency medical care. The following hospital Setting – Paramedic – drugs, airway and breathing equipment), digest summarises the principles of Emergency Physician drug administration, temporary manual prehospital analgesia, sedation and in-line stabilisation of the cervical spine emergency anaesthesia. 52 Review Articles Medical Education

Analgesia level of standards with regard to patient Pain and its possible causes can be safety as treatment by an emergency classified using the so-called OPQRST Preliminary remarks physician would be. mnemonic (documentation of onset, pro-­ Following initial emergency care vocation and palliation, quality, region (ABCDE-algorithm) to avert threats to Sufficient analgesia is an important and radiation, severity, time [duration life, pain should be ascertained and component of qualified emergency and course]; Table 2) [14]. treated [1]. Pain is a common reason medical care and a necessity if further The numeric rating scale (NRS) has for activation of the EMS and brings threats to life and complications are established itself as a prehospital tool with it an inherent requirement for an to be averted. for quantitative assessment of pain and emergency physician [2]. Trauma is response to analgesic management. The the most common cause of prehospital Prehospital analgesia not only increases patient is asked to rate the intensity of pain, followed by chest and abdominal patient comfort, but is actually physio- their pain on a scale of 0 – 10 (0 = no pain (Table 1) [3]. The degree to which logically valuable: pain ranging to 10 = most severe pain pain is alleviated is a significant factor • pain causes a sympathoadrenal imaginable). A requirement for prehospi- in patients’ perception of quality of care response (e.g. sweating, tachycardia, tal analgesia is assumed from a value of received. However, research shows that hypertension, hyperventilation) 4 upwards, heightening from there with <60% of patients with cardiopulmonary and increases myocardial oxygen the reported intensity. The aim of treat- disease, <50% of trauma patients and requirements. ment is to provide sufficient analgesia by only approximately 30% of patients with • Local inflammation with release reducing the NRS to <4 or by 3 points abdominal pain receive sufficientanal ­ of cytokines and nociceptor sensi- whilst avoiding complications and side gesia in the prehospital setting [4-11]. Pro- effects [5]. Analgesic management in tization can promote development viders argue the following causal factors: a prehospital setting can employ phar- of hyperalgesia and chronification • age or origin of the patient; macological and non-pharmacological of pain. • limited ability to communicate; means as well as supportive measures • Increased muscle tone and avoid- • willingness to endure pain. (such as repositioning the fracture, ance behaviour caused by pain can positioning the casualty, and verbal In some cases, however, provider in- lead to relevant hypoventilation and emotional support). security leads to omission of analgesic thus cause hypoxaemia [12]. therapy (e.g. concern surrounding re-­­ spiratory depression as a side effect of Qualitative and quantitative Pain can be assessed using the nu­ treatment [with opioids]) [11]. ­assessment of pain meric rating scale (NRS). The aim of That sufficient treatment for pain be Various systems are available for detec- analgesic management should be to provided as a basic measure by EMS tion and quantification of pain, for in- reduce to the NRS to under 4. and emergency physicians should be terpretation of the character of pain and demanded in this day and age. Pro- for confirmation of the diagnosis. Pain Checklist for use of analgesics gressive professionalisation of the EMS should be asked after and documented Use of analgesics is subject to the fol- (e.g. the institution of “Notfallsanitäter” whenever emergency care is provided. A lowing prerequisites: – the German equivalent of a trained complete registration of vital signs pro- • Assess and document intensity of and licensed paramedic) has led to vides important information regarding pain (using the NRS). the introduction of standard operating physiological reactions (e.g. tachypnoea • Elicit a thorough history (e.g. procedures and treatment pathways for as an expression of pain) [13]. standardised “SAMPLER” history analgesia and analgosedation which must, however, be subject to the same Table 2 “OPQRST“ mnemonic (modified from [14]). Table 1 Incidence of pain in relation to prehospital O (Onset) onset/time/situation/trigger diagnosis groups (modified from [3]). P (Palliation/Provocation) palliating/provoking factors (e.g. movement) Primary diagnosis Prehospital Q (Quality) character of pain: colicky, spasmodic, sharp, dull group incidence R (Radiation) localisation and radiation of pain Trauma 50–55% S (Severity) intensity of pain scored on NRS Chest pain 27–34% T (Time) duration and course of pain since onset Abdominal pain 7–21% NRS: Numeric Rating Scale Medical Education Review Articles 53

[symptoms, allergies, medication, for securing the airway should be therefore relief beyond the prehospital past pertinent medical history, last immediately available [17,18 ] . setting, should be considered. All in all, oral intake, events leading up to • The provider (regardless of whether only a small selection of low-potency current situation, risk factors] in emergency physician or paramedic) analgesics is available to German EMS accordance with various emergency must be in a position to treat side and emergency physicians [20]. medicine course concepts), paying effects attributable to the employed attention to allergies. drugs safely and competently. Prehospital pain management should • Assess risk: Fasted? Allergies? Past be multilevel if required and include medical history? Time to hospital? Close monitoring is a requirement a combination of different analge­ • Choose drugs based on indication, for any analgosedation: depending sics. experience of the emergency on the drugs used there is a fine line physician and regional protocols between sufficient analgesia and re­ (e.g. standard operating procedures/ lative overdose impeding on vital Non-opioid analgesics treatment pathways specific to functions (causing e.g. loss of con­ Paracetamol the particular emergency medical sciousness, respiratory depression Intravenous administration of paraceta- service, availability). and circulatory collapse). As such, mol has a relatively small analgesic • Obtain informed consent when in addition to standard monitoring effect [21–25]. When administered for required, including and especially and prophylactic oxygen insufflati­ fractures of the limbs, paracetamol when analgesia is provided by on, titrating drugs to effect is expedi­ does not provide adequate analgesia. paramedics. ent. Furthermore, any equipment • Establish secure intravenous access It does, however, exhibit very good necessary for securing the airway (test for backward flow, free flowing antipyretic effects and can be indicated should be immediately available. IV fluids), using alternatives if in appropriate prehospital settings (e.g. required when peripheral venous fever) [26]. As setron-type antiemetics access is unavailable: Supportive non-pharmacological [5-HT3 antagonists (e.g. ondansetron)] - Intranasal administration (e.g. measures can influence the effect of paracetamol, fentanyl, ketamine/esketamine, this combination should be avoided in Non-pharmacological measures include midazolam) [15] the prehospital setting [27]. - Intraosseous administration (dose repositioning, in-line stabilisation and as for intravenous administration) local cooling for trauma of the limbs, Metamizole [16] but also comfortable patient positioning Metamizole exhibits a spasmolytic com­ - Intramuscular administration (as a (e.g. knees drawn up and supported for ponent (Table 3). Its delayed onset of measure of last resort for selected abdominal or lower back pain) [19]. action is a disadvantage. Major side drugs, e.g. ketamine/esketamine Verbal emotional support provided by effects include emergency medical professionals and or for burns) • a possible drop in blood pressure the emergency physician play an • Establish standard monitoring for (particularly following rapid intra­ equally decisive role and can positively analgosedation: respiratory rate, venous injection) and in­fluence the individual experience of pulse oximetry, ECG and blood • allergic reactions. pressure, capnography even for pain. For children especially, involving Metamizole is used commonly in hospi- spontaneously breathing patients. an attachment figure is of importance. tal and prehospital emergency situations • Avoid overdosing by titrating to Availability and selection of [28]. Whilst often-cited, agranulocytosis effect (“as much as necessary, as little as possible”). Take the age and ­analgesics is a very rare side effect which does, condition of the patient (e.g. haemo- According to the WHO pain ladder, however, have to be included in an dynamics) into account, reducing the analgesic management should be started informed consent conversation [29]. dose when necessary and waiting with non-opioid analgesics. For acute Equally, pancytopenia and its typical an appropriate length of time before pain (an intensity of NRS 4 or above), symptoms should be included. Whether administering further doses. however, the initial treatment should be or not informed consent can be obtained • Administer oxygen (via nasal cannula with potent analgesics administered at a from a patient suffering pain should be or non-rebreather mask) whenever sufficient dose to achieve rapid remission. judged on an individual basis. There is opioids and ketamine/esketamine Especially when short-acting analgesics discussion surrounding an attenuating in combination with midazolam (e.g. ketamine) are used, a combination effect of metamizole on the effect of are used, as these drugs can cause with longer-acting analgesics providing long-term ASA on platelet inhibition respiratory depression. Options an overlapping or extended effect, and [30–32]. 54 Review Articles Medical Education

Table 3 Peripheral analgesics (modified from [67]).

Drug Indication Dose Mode of action Contraindications Notes Paracetamol Mild to 15 mg/kg BW IV Cyclooxygenase inhibition in CNS Risk of intoxication in small Antidote in case of intoxi­- moderate 4 g maximum daily Metabolised via cytochrome P450 children, the elderly, liver cation: N-acetylcysteine pain disease, alcohol abuse, dose for adults Possible 5-HT3 receptor Drug effect possibly im­- Fever concomitant use of other drugs paired by concomitant mediated spinal inhibition causing enzyme induction administration of 5-HT3 antagonists (e.g. ondan­- setron) Metamizole Colic 15 mg/kg BW IV Pyrazolone derivative In emergencies no dose Slow IV push (caution: Acute 1 g IV single dose Active metabolite: 4-N-methyl­ adjustment required for renal or hypotension) severe pain aminoantipyrin hepatic impairment. For Anaphylaxis 5 g maximum daily long-term use reduce dose. Fever dose Peripheral und central COX II Rare: Agranulocytosis inhibition Contraindications:  informed consent required Mild antiphlogistic analgesic asthma syndrome Spasmolytic Metabolites found in impaired bone marrow function breast milk Mild antipyretic glucose-6-phosphatase Bioavailability 90% dehydrogenase deficiency acute intermittent hepatic porphyria pregnancy (final trimester)

Ketamine/esketamine zolam) for analgosedation (caution: Agranulocyto-sis is a very rare side respiratory depression). effect of metamizole which does, In analgesic doses, ketamine, an NMDA antagonist, exhibits a rapid and potent however, have to be included in an onset of action without impacting on Hypersalivation caused by ketamine informed consent conversation. In­ spontaneous breathing or airway protec- can be treated particularly in children formed consent should be obtained tive reflexes (“dissociative analgesia”). by weight-adjusted administration of in a fashion adapted to the situation, Side effects include atropine. Due to hyperacusis, patients although the patient should be infor­ • hallucinations, should be provided with hearing pro­ med of possible symptoms even in an • hypersalivation, tection during technical rescue and emergency situation. • hyperacusis and transfer to hospital. • nystagmus. The enantiomer esketamine (S-ketamine) Table 4 sets out an overview of onset and Central stimulation of the sympathetic is a more potent analgesic and anaes- duration of action of various analgesics. nervous system leads to an increase thetic (observe altered dosing regimen). in heart rate and blood pressure with Because ketamine is not a controlled Table 4 a consecutive increase in myocardial substance under German law, it is re­ Onset and duration of action of analgesics oxygen requirements. Whilst this effect commended for use by emergency medi­ (modified from [51]). cal professionals as a potent analgesic is desired especially in hypovolaemic for predefined conditions (e.g. trauma Agent Onset Duration trauma patients or those with haemody- pain following injuries to the limbs). of action of action namic instability, it represents a relative (min) (min) Numerous EMS stipulate analgosedation contraindication in patients at risk of provided by paramedics for trauma Metamizole IV 15–30 240 cardiac complications or exhibiting pain using ketamine and midazolam Ketamine/ 0.5 5–10 hypertension­ [33]. Use of ketamine for in accordance with fixed algorithms. esketamine IV patients with head injuries whilst moni­ This reduces the time to treatment prior Ketamine/ 5–10 12–25 toring with capnography is deemed esketamine IN to arrival of an emergency physician; established current practice and is not convincing data demonstrate the safety Morphine IV 5–10 30–120 contraindicated [34,35]. of this approach [36-38]. Guidelines, Fentanyl IV 1 20–40 training and certification of each indi- Fentanyl IN 5–10 30–60 As ketamine can cause nightmare- vidual employee rest with the respective Piritramide IV 5–20 40–60 like conditions, it is typically com­ medical director of EMS within the prin- bined with a sedative (e.g. mida­ ciples of delegation. Ketamine can also Medical Education Review Articles 55

be administered nasally, orally, rectally Intravenous fentanyl exhibits a rapid Sedation and intramuscularly. Intranasal use in analgesic effect but also a high potential particular is suitable for analgesia in for respiratory depression; it can, how- When treating aroused, anxious or children, although this mode of delivery ever, be used – carefully titrated – for panicking patients, or those suffering constitutes off-label use [39,40]. analgesia in spontaneously breathing psy­chiatric emergencies, and as a sup- patients (caution: observe breathing Opioids portive measure in various other emer- closely). Ideally, capnography should be In prehospital settings, morphine and gency situations such as for technical used even in spontaneously breathing fentanyl, and less commonly sufentanil rescue, sedation may be required when patients. In addition to intravenous and and piritramide are provisioned. Both verbal interventions (e.g. talk down, intranasal routes, fentanyl is suitable for sufentanil and fentanyl are not approved calming the patient, creating a calm buccal or mucosal administration [44]. for use as analgesics outside general atmosphere) are insufficient. Benzo­ anaesthesia, however. Opioids exhibit Sufentanil is especially suited to induc- diazepines not only exhibit an anxiolytic differing analgesic, sedative and antitus- tion of general anaesthesia. When used effect, but also have additional somatic sive properties. Side effects include for analgesia in spontaneously breathing effects (e.g. reduction of myocardial • respiratory depression, patients, the risk of respiratory depression oxygen requirements). With regard to must be observed. Piritramide, which is • sedation, the indication for and monitoring of made available by some EMS, exhibits • bradycardia, sedation the same requirements should a delayed onset of action similar to that • hypotension, be met as for analgesia. • pruritus, seen in morphine [22]. However, many In addition to use of benzodiazepines (e.g. • bronchospasm, emergency physicians have experience • sweating and with this drug by the use in a hospital midazolam, lorazepam) in emergency • miosis. setting. Current research shows no care, morphine is used for analgoseda- advantage in use of a specific analgesic­ tion in patients undergoing non-invasive In emergencies, there are no contrain­ (fentanyl vs. morphine, opioids vs. keta- ventilation (NIV). Neuroleptics (e.g. halo­- dications to opioid use. This remains mine) [19]. peridol) are no longer widely made avail- true even during pregnancy and breast-­ feeding, when risks and benefits would Increasingly, paramedics are using able by EMS and are reserved for specific otherwise have to be considered care­ opiates and opioids in accordance with indications [50]. fully. Antiemetic co-medication (e.g. on­- fixed algorithms within the scope of Benzodiazepines can be administered dan­setron, dimenhydrinate) can be used delegation and without the presence of intravenously but also via the nasal or a physician [45,46]. In some cases, a if required. Doses should be titrated buccal routes, offering an advantage in system of telephoned orders (so-called when treating geriatric patients, particu- those patients who are so agitated that “call-back” procedure) has been estab- larly to avoid respiratory depression [41]. venous access cannot initially be estab- lished [47]. Morphine is significantly less potent lished. (Side) effects are than fentanyl (1:100) and has a delayed When comparing analgesic regimens • anxiolysis, onset of action at 5 to 10 minutes. As using morphine, fentanyl and keta­ • amnesia and such, repeat doses should not be ad- mine, available research shows no • dose-dependent respiratory ministered too quickly. Morphine offers clear superiority of any one sub­ depression. advantages especially when used for stance over the other. Low dose propofol can also be used myocardial infarction, where its sedative for sedation, especially when use of and parasympathomimetic properties (e.g. bradycardia) are desirable. In addi- Further substances with analgesic effects benzodiazepines is contraindicated or tion, the reduction of pulmonary vascu- In some countries (e.g. the United shows insufficient effect. That propofol is lar resistance is an advantage over other Kingdom), nitrous oxide has been used easily controlled is of advantage in these analgesics. Despite providing sufficient for decades by emergency medical situations. analgesia, morphine is at a disadvantage professionals to treat pain in prehospital when treating trauma patients because settings. Nitrous oxide is used by inhala- Patients undergoing sedation with of its delayed onset of action – position- tion as a fixed combination with oxygen propofol must – as with any other ing the patient or repositioning a fracture (e.g. Entonox®, 50% nitrous oxide, 50% drug – be observed closely for airway in particular call for rapid onset of an- oxygen) [48]. Studies show an effect obstruction through regurgitation/ algesia [42]. Newer research shows that especially for trauma pain [49]. Indi- aspiration and for respiratory de­ morphine may exhibit an unfavourable vidual EMS in Germany provide nitrous pression at all times. In addition to effect on thrombocyte function and size oxide/oxygen mixtures for pain relief for obligatory monitoring, equipment of infarction in patients with ST-elevation administration by emergency medical for airway management must be myocardial infarction [43], although this personnel; this is currently not standard held available. is not yet relevant to treatment. practice, however. 56 Review Articles Medical Education

Prehospital emergency • traumatised patients suffering severe have good command of concepts for in- thoracic injuries, respiratory or duction and maintenance of emergency anaesthesia cardiovascular instability or head anaesthesia and be able to anticipate injuries (Glasgow Come Scale GCS possible complications [54]. Preliminary remarks <9) and Induction of prehospital emergency • patients suffering life-threatening The emergency physician is called anaesthesia is a task reserved for the neurological emergencies (e.g. status upon to critically evaluate the indi­ emergency physician and represents epilepticus). cation for emergency anaesthesia, a central therapeutic measure in emer- taking risks and benefits into ac­ gency care [51–54]. The S1 guideline on count and ultimately – together with “prehospital emergency anaesthesia in In summary, emergency anaesthesia the whole team – deciding on a clear adults” [54] observes that emergency is indicated in those patients with concept for anaesthesia including physicians – regardless of their speciality acute or impending disruption of alternatives. – must be competent to autonomously oxygenation­ or ventilation in whom and safely induce emergency anaes- conservative management (incl. NIV) thesia in the context of a variety of is insufficient and in those with im­ injuries, diseases and risks, even when paired consciousness with a conse­ Special considerations complicated by the prehospital setting. cutive risk of aspiration [54]. Preliminary remarks Induction itself poses a challenge to Emergency anaesthesia is associated the whole team, especially as the pre- The aims of anaesthesia and airway with an increased risk of complications hospital setting is not comparable with man­agement are to secure the airway, [56,57]. In accordance with the DGAI elective routine anaesthesia. Assistance uphold oxygenation and ventilation (nor­- recommendations regarding prehospital offered by emergency medical personnel mocapnia), provide sufficient analgesia, airway management, multifactorial risk- – including prior consultation with the reduce oxygen requirements and ulti­ inducing conditions can be charac- whole team – is an important requisite mately avoid secondary myocardial and terised by provider-specific, patient or for safe execution, avoiding complica- cerebral damage [54]. The indication for scenario-related factors [53]. tions [55]. and planning and execution of emer- Patient-related factors The following elaborations are based on gency anaesthesia are influenced by recommendations made by the German various factors [54]: Emergency patients must be considered Society of Anaesthesiology and Inten- • training, practical experience and non-fasted with a high risk of aspiration: sive Care Medicine (DGAI) and the S1 capabilities of the emergency RSI with rapid induction of anaesthesia guideline on “prehospital emergency physician and emergency medical should be employed and the airway anaesthesia in adults” [54]. personnel, secured without intermediate mask ven- • environmental factors on scene tilation. Anatomic features and airway Critical considerations (e.g. light, available space and injuries (e.g. intraoral haemorrhage, In general, the requirement for prehos­ weather conditions), midfacial fractures) must be evaluated pital emergency anaesthesia is influ- • transfer time and type (ground or prior to induction for their potential to enced by a number of factors and it is air transport), cause difficult intubation.Reduced mo­ the duty of the emergency physician • circumstances surrounding airway bility of the cervical spine (pre-existing, – following careful appraisal of the management with specific regard traumatic or through immobilisation) situation as a whole – to review the to the patient and signs of difficult is a patient-related risk factor, as are indication and determine a suitable pro­ intubation (e.g. expected difficult cardiopulmonary and other impairments cedure [54]. airway in an emergency patient with caused by pre-existing disease and/or First and foremost, reversible causes im- sufficient spontaneous breathing). injuries (e.g. haemorrhagic shock when peding vital functions (such as hypo­gly­- Emergency anaesthesia encroaches on blood loss is often underestimated, the caemia causing unconsciousness) should bodily integrity and is associated with a number of oxygen carrying erythrocytes be excluded. The following constella- relevant mortality risk. It is as such that is critically reduced and there is a risk tions are typical situations requiring the emergency physician must as part of serious decrease in blood pressure). prehospital emergency anaesthesia, se­- of a risk/benefit analysis consider the The patient’s medication should be curing the airway: possible disadvantages and risks (e.g. taken into consideration (standardised • sustained impaired consciousness vomiting, aspiration, airway obstruction, “SAMPLER” history). It is recommended with risk of aspiration (e.g. cardiovascular depression, allergic re-­ that peripheral venous access should be suspected intoxication, intracranial actions) associated with emergency gained at two sites and that intraosseous haemorr­hage), anaesthesia. These risks make it essential access be considered when venous • acute respiratory distress, that every emergency physician should access is difficult. Medical Education Review Articles 57

Scenario-related factors rapid succession. An analgesic can be muscular block (in adults typically The position of the patient can be rele- administered prior to or immediately without intermediate ventilation). vant with regard to anaesthesia: patients after these two drugs, or after the airway • In individual cases, intermediate trapped or partially inaccessible can be has been secured. Any necessary equip- ventilation may be required to rescued following analgosedation with ment must be prepared and emergency maintain oxygenation irrespective of preserved spontaneous breathing, later resources (e.g. alternative means of the risk of aspiration [60]. undergoing induction of anaesthesia in securing the airway) ready to hand [53]. • Change to an alternative (e.g. supra­ a more favourable location (e.g. in the The following points are important: glottic airway) following a maximum • Begin preoxygenation as early as paramedic unit) under optimised condi- of 2 intubation attempts. Perform possible at the same time as pre- tions. The limited range of emergency intermediate ventilation if necessary. paring anaesthetic and emergency equipment and a limited selection of • Inflate the cuff on the endotracheal drugs for induction of anaesthesia should drugs; whenever justifiable extend over at least 3 – 4 minutes using tube or supraglottic airway (SGA, be taken into consideration. In addition, e.g. laryngeal mask, laryngeal tube) as a rule, induction of emergency anaes­ 100% oxygen via a non-rebreather immediately after insertion. thesia is time critical such that depend- mask or a tight sitting bag valve • Check the correct position (e.g. ing on the specific situation it usually mask using an oxygen reservoir capnography, video laryngoscopy, occurs under pressure. (minimum 12 – 15 l O2/min). Use of a demand valve or non-invasive ven- auscultation) and securely fix in place. Organising prehospital emergency tilation (NIV) is both more effective • Maintain anaesthesia, use catecho- anaesthesia comprises the following and saves oxygen [54,58–60]. lamines if required, adjust and points: • Establish optimum monitoring of re-evaluate the respirator settings • thorough evaluation and exami­ vital signs using pulse oximetry (define and check target values, nation of the patient, (SpO2) with heart rate and oxygen capnography). • critical evaluation of the indica­ saturations (pulse tone as an acoustic signal), 3-lead ECG (heart tion for prehospital emergency During anaesthesia, aim for normoxia, rate and rhythm), automatic blood anaesthesia, normocapnia, a sufficient depth of • optimisation of the patient’s pressure monitoring at close intervals (minimum 3 minutes, every anaesthesia and haemodynamic sta­ ­condition through preoxygena­ bility. tion, haemostasis and fluid minute if possible) and capnography. therapy (if required), • Prepare anaesthetic and emergency • standardised preparation for drugs. Use sticky syringe labels in Standard monitoring must be used and execution of prehospital accordance with the DIVI recom- throughout anaesthesia so as to provide emergency anaesthesia, mendations if possible – if not, it is professional care and to recognise and • managing complications. indispensable syringes be labelled in respond to changes in vital functions writing [61]. in a timely fashion. In case of changes • In so far as not impermissible (e.g. or abrupt complications (e.g. a drop in Preparing for and carrying out spinal immobilisation in trauma SpO2) a re-evaluation along the lines of emergency anaesthesia patients, haemodynamically unstable the ABCDE-algorithm is a must. When The decision to undertake emergency an- patients) elevate the upper body airway complications are suspected, aesthesia is communicated to the whole (e.g. in-line). the mnemonic “DOPES” (dislocation, medical team. Together, a decision is Check venous access (test for backward taken where anaesthesia should be obstruction, pneumothorax, equipment, flow, connect IV fluids): stomach [hyperinflation]) can be helpful induced (e.g. in the patient’s home vs in • Begin induction of anaesthesia fol­ in systematically detecting the cause, the paramedic unit), tasks are allocated, lowing team briefing and allocation particularly in emergency situations and the choice of anaesthetic drugs and of tasks. (Table 5) [62]. necessary doses are discussed together • Drugs and doses (in ml and mg) with any important details and instruc- should be called out by the emer- tions. This way, the team determines the gency physician and confirmed by Acute changes to vital signs (e.g. a approach to emergency anaesthesia, emergency personnel (“closed-loop” drop in SpO2, an increase in inspira­ which should ideally be oriented toward communication). tory pressure) following induction or a standardised process [54]. In addition, • In patients with an immobilised during maintenance of anaesthesia alternatives should be agreed upon and cervical spine, have an additional must trigger immediate re-evaluation prepared [54]. helper perform manual in-line in accordance with the ABCDE-algo­ Induction of emergency anaesthesia is as stabilisation (MILS) [59]. rithm, so as to rapidly detect and a modified RSI, administering a hypnotic • Secure the airway following loss of rectify the cause. and a neuromuscular blocking agent in consciousness and onset of neuro- 58 Review Articles Medical Education

Table 5 guideline on “prehospital emergency “DOPES“ mnemonic for acute airway problems in intubated patients (modified from [62]). anaesthesia in adults” [54]: Trauma/multiple trauma: Table 6 lays D  Dislocation (endotracheal tube disconnected? Check breathing system!) out a suggestion for standardised pre- O Obstruction (bronchospasm following induction of anaesthesia  auscultation, capnography) hospital emergency anaesthesia in the P Pneumothorax (auscultation? Inspiratory pressure? Trauma?) context of major (multiple) trauma using E Equipment (ventilator and monitoring intact? Breathing system set up correctly? Leaks? a selection of suitable drugs. In that  Examine the whole system) context, haemodynamic instability due S Stomach (paediatric patients especially may have suffered gastric insufflation during mask to hypovolaemia must be taken into con- ventilation  insert a gastric tube or suction air once-off) sideration. Ketamine with midazolam is especially suitable for induction of anaesthesia and adequate fluid adminis- Managing complications and Anaphylactic reactions can potentially tration during induction is essential. problems be caused by any anaesthetic agent, Isolated neurotrauma, apoplexy, intra­- especially by neuromuscular blocking ­cranial haemorrhage: Drugs which lower Complications must be recognised agents. In such cases, standardised man­­ intracranial pressure such as propofol or rapidly and rectified in a structured and agement (e.g. glucocorticoids, H1/H2 thiopental are particularly suitable for consequent fashion. A difficult airway receptor blockers and adrenaline IV) induction of anaesthesia and can help must be anticipated in the prehospital must be instigated immediately. Aspi­ avoid blood pressure spikes (with con- setting. Generally speaking, video laryn- ration and oral, nasal and pharyngeal secutive increased intracranial pressure) goscopy is an option which can optimise haemorrhage have been reported with associated with inadequate depth of intubation conditions even when the an incidence of 14 – 20% [65] – as such anaesthesia. patient cannot be ideally positioned, it is crucial suction should be available High cardiac risk patients: Anaesthetics or neck extension is limited. For trauma immediately. As hypoxia can arise with drugs such as midazolam, etomidate, patients in particular, video laryngoscopy an incidence of 5 – 18% [66], effective fentanyl or sufentanil which exert only should be used from the outset [59]. A preoxygenation is essential, reducing the minor effects on the cardiovascular return to spontaneous breathing can risk of hypoxia due to failed or delayed system (shifts in inotropy, preload and hardly be put into effect when an unex- airway management [60]. afterload) should be preferred. pected difficult airway is encountered Patients in respiratory failure: rapid-­ in a prehospital setting. Instead, think­- Concepts in anaesthesia for acting drugs should be used for induc- ing forwards, a sufficient airway man- ­miscellaneous emergencies tion of anaesthesia. Ketamine may be agement strategy must be enacted. The following concepts for anaesthesia indicated specifically for its bronchodi- Following a maximum of two intubation are based on suggestions in the S1 latory effect. attempts (intermediate ventilation!) a switch should be made to an alternative approach, initially using a supraglottic Table 6 airway but moving on to establish a Emergency anaesthesia in patients with severe trauma (modified from [54]). surgical airway (cricothyrotomy) as a Example: motor vehicle accident, 25-year-old male, SBP 110 mmHg, HR 96 bpm, SpO2 88%, measure of last resort if required [53]. body weight approx. 70 kg, head injury, chest injury, open right femur fractur, left upper ankle An insufficient depth of anaesthesia can joint fracture, currently still trapped in his vehicle. lead to movement, laryngo- and bron- Analgosedation maintaining spontaneous breathing during the extrication phase: midazolam 3 mg IV chospasm and awareness. Manipulation + esketamine 25 mg IV (bolus 10 mg approx. every 20 min if required) of the patient should be suspended, and + fluid resuscitation using suitable fluids IV the depth of anaesthesia increased. Prepare for anaesthesia and preoxygenate The incidence of hypotension following Induction of thiopental 200 mg or midazolam 7 mg or propofol 100 mg IV prehospital induction of anaesthesia is anaesthesia* + esketamine 100 mg or fentanyl 0.2 mg or sufentanil 20 µg IV 7 – 18% [63,64]. Use of standard moni­ + rocuronium 70–100 mg or succinylcholine 100 mg IV toring including oscillometric blood Secure airway* increase depth of anaesthesia with midazolam 3–5 mg IV if required pressure measurements at close intervals Maintenance of midazolam 3–5 mg IV (repeat approx. every 20 min) is essential. Depending on the patient’s anaesthesia* + esketamine 20 mg (repeat approx. every 20 min) or fentanyl 0.15 mg IV (repeat approx. every 20 min) situation, fluids should be administered + rocuronium 20 mg IV (repeat approx. every 20 min) and vasopressors be utilised early (e.g. * Haemodynamic support using noradrenaline 10 μg boli as required to attain SBP goal or via syringe cafedrine/theodrenaline, noradrenaline driver. e.g. 10 µg boli IV or possibly adrenaline). Medical Education Review Articles 59

Drug Overview side effects are exacerbated in patients cause myoclonus (caution: this may lead with cardiovascular failure and hypo- to difficult mask ventilation) and admin- Preliminary remarks volaemia especially. As such, propofol istration should therefore be preceded This section provides an overview of should be used for RSI only in haemo- by a benzodiazepine. Irreversible inhibi- the most commonly used drugs in the dynamically stable patients and the tion of cortisol synthesis in the adrenal context of induction and maintenance dose should be adapted appropriately. gland has been reported, which has led of anaesthesia in an emergency medical With regard to anaesthesia, propofol to increasing use of alternatives or even setting. Generally speaking, to avoid exhibits only hypnotic effects and a short substitution of etomidate. With regard to critical hypotension or complications duration of action – maintenance of intubation success and haemodynamic ranging from cardiac failure to cardiac anaesthesia requires alternative drugs stability, ketamine is seen as equivalent arrest, drugs used for analgesia and (e.g. midazolam) or – for haemodynam- to etomidate and should as such be emergency anaesthesia should be dose ically stable patients – continuous ad- favoured when treating trauma patients adapted or titrated to effect especially ministration of propofol 2% via syringe [59]. in critically ill patients and those in car­ driver. Its ability to reduce intracranial Midazolam: this rapid but short acting diorespiratory failure. pressure and its anticonvulsive effect benzodiazepine has a broad therapeutic Hypnotics can be put to use when it is used for in- index (Table 7). Midazolam has a plasma Propofol: as the arguably most com- duction of anaesthesia in head injuries, half-life of 1.5 to 2.5 hours – notably monly used induction-agent in the in- intracranial haemorrhage and status longer than that of etomidate – and can hospital setting, propofol is also made epilepticus. be used in various combinations for in- available in many EMS (Table 7). It Etomidate: this purely hypnotic induc­ duction of anaesthesia, although not as causes respiratory depression and a de- t­ion agent is still made available in monotherapy. A combination with opioids crease in blood pressure by moderating numerous EMS for its propensity to (e.g. midazolam/fentanyl) is common, sympathoadrenal stimulation and reduc- provide haemodynamic stability during as is the combination with ketamine. ing peripheral vascular resistance. These induction of anaesthesia (Table 7). It can Midazolam is especially suited to main­-

Table 7 Hypnotics (modified from [54]).

Drug Dose Mode of Action Side effects Notes Propofol Induction of anaesthesia: GABA receptor agonist Respiratory depression or Mild bronchodilatory effect, (1–) 1.5 – 2.5 mg/kg BW IV apnoea, decreased blood favourable effects in head injuries Maintenance of anaesthesia: 3 pressure (negative inotropic and increased ICP (4) – 6 (–12) mg/kg BW/h IV or effect, reduced peripheral bolused as required vascular resistance) especially in 0.25 – 0.5 mg/kg BW IV the presence of hypovolaemia, excitation phenomena, injection Onset of action: 15 – 45 s pain, histamine liberation Duration of action: 5 – 10 min Etomidate Induction of anaesthesia: Not conclusively established, Nausea and vomiting, mild Impairs cortisol synthesis (11β-hydro­ 0.15 – 0.3 mg/kg BW IV hypnotic effect partially respiratory depression, xylase) even following single use, Onset of action: 15 – 45 s exerted via a GABAergic injection pain, myoclonus increasing the risk to patients suffering mechanism trauma or sepsis of complications Duration of action (half-life): such as ARDS, multiorgan failure, 3 – 12 min increased hospital and/or intensive care length of stay, increased duration of mechanical ventilation, increased mortality Midazolam Induction of anaesthesia: Binds to the α-subunit on the Paradoxical excitation Caution: Dosing errors due to 0.15 – 0.2 mg/kg BW IV GABA receptor effecting Caution: combination with mix-up when multiple different Maintenance of anaesthesia: prolonged opening of alcohol (alcohol effects concentrations are provisioned 0.03 – 0.2 mg/kg BW IV chloride channels and with increased), respiratory [5 mg/5 ml (=1 mg/ml) ampoules that an increased effect of depression when combined and 15 mg /3 ml (= 5 mg/ml) Onset of action: 60 – 90 s the inhibitory CNS with opioids ampoules] Duration of action (half-life): transmitter GABA. 1 – 4 h Thiopental Induction of anaesthesia: GABA receptor agonist Respiratory depression, Powder for solution, requires 3 – 5 mg/kg BW IV hypotension, reconstitution prior to use Onset of action: 10 – 20 s histamine liberation Caution: paravascular administration Duration of action: 6 – 8 min causes necrosis 60 Review Articles Medical Education

Table 8 Analgesics (modified from (67)].

Drug Dose Mode of action Side effects Notes Morphine Titrate to response, Pure opioid receptor agonist with Respiratory depression, muscle Antidote: naloxone e.g. 2.5 mg boli IV high affinity to µ receptor and rigidity, hypotension especially Histamine liberation 10 mg/1 ml low affinity toκ receptor in the context of hypovolaemia, Active metabolites morphine-6- emesis, nausea, bradycardia, Reduces pulmonary vascular glucuronide and morphine-3- pruritus, bronchospasm, resistance glucuronide which can sedation cumulate in the presence of Hydrophilic, and as such delayed renal failure onset of action (5 – 15 min) Duration of action 3 – 5 h

Piritramide Analgesia: 0.1 mg/kg Potency 0.7 (morphine Respiratory depression equivalency) muscle rigidity 7.5 mg/1 ml Onset of action after 5 – 15 min hypotension especially in the 15 mg/2 ml Duration of action 3 – 4 hours context of hypovolaemia bradycardia

Fentanyl Analgesia: titrate to response, Pure opioid receptor agonist Respiratory depression Antidote: naloxone 0.05 – 0.1 mg IV boli with high affinity to µ receptor muscle rigidity Store protected from light 0.1 mg/2 ml and low affinity toκ receptor Induction of anaesthesia: hypotension especially in the May cause chest wall rigidity 0.5 mg/10 ml start with 2 µg/kg BW IV context of hypovolaemia Maintenance of anaesthesia: bradycardia 1 – 3 µg/kg IV Onset of action: <30 s Duration of action (median): 0.3 – 0.5 h

Sufentanil Start with 0.15 – 0.7 µg/kg IV Pure opioid receptor agonist Respiratory depression Antidote: naloxone + 0,15 µg/kg IV repeat doses with high affinity to µ receptor muscle rigidity Store protected from light and low affinity toκ receptor Onset of action: <2 – 3 min hypotension especially in the Duration of action (median): context of hypovolaemia 0.2 – 0.3 h bradycardia

Esketamine 0.25 – 0.5 mg/kg BW IV for Non-competitive NMDA Sympathomimetic; increases Esketamine does not increase analgesia preserving receptor antagonist heart rate and blood pressure, ICP and can be used in the protective reflexes. presence of head injuries. Use Agonist effect on opioid respiratory depression ranging with caution in the context of Induction of anaesthesia: receptors to apnoea, severe heart failure. Do not 0.5 – 1 mg/kg BW IV or increased defensive reflexes in Inhibits peripheral catecholamine store under 0° C as vial may 1.5 – 5 mg/kg IM the pharyngeal and laryngeal reuptake shatter. Onset of action (IV): 30 s regions (caution: laryngospasm Influences central and peripheral Duration of action (IV): when suctioning or intubating), monoaminergic and cholinergic 5 – 15 min anxiety, hallucinations neurotransmission, produces dissociative anaesthesia

Ketamine 0.5 – 1 mg/kg BW IV for Non-competitive NMDA Sympathomimetic; increases Ketamine does not increase analgesia preserving receptor antagonist heart rate and blood pressure ICP and can be used in the protective reflexes. presence of head injuries. Use Agonist effect on opioid respiratory depression ranging with caution in the context of Induction of anaesthesia: receptors to apnoea severe heart failure. Bronchodi- 1 – 2 mg/kg BW IV or increased defensive reflexes in Inhibits peripheral catecholamine latory effect in asthma. Do not 4 – 10 mg/kg IM the pharyngeal and laryngeal reuptake store under 0° C as vial may Onset of action (IV): 30 s regions (caution: laryngospasm shatter. Duration of action (IV): Influences central and peripheral when suctioning or intubating), 5 – 15 min monoaminergic and cholinergic anxiety, hallucinations neurotransmission, produces dissociative anaesthesia Medical Education Review Articles 61

Table 9 Neuromuscular blocking agents (modified from (54)].

Drug Dose Mode of action Side effects Notes Succinyl­ Single, on-off dose: Only depolarising neuro­- Arrhythmias, tachycardia, brady- Increased sensitivity in the context choline in all age groups muscular blocking agent; cardia, potassium liberation ranging of neuromuscular disease (reduce 1.0 – 1.5 mg/kg BW IV exerts its effect on the to asystole, blood pressure changes dose in necessary), pre-treatment Onset of action: 60 - 90 s nicotinic acetylcholine muscle pain following fasciculations with non-depolarising agent (ACH) receptor at the mitigates side effects, noteworthy allergic reactions Duration of action: 3 – 6 min motor end plate rigor of the masseter muscle is increased intraocular pressure deemed to be a warning sign for (caution: penetrating injuries) rhabdomyolysis or malignant increased gastric pressure hyperthermia, duration of action increased salivation increased in the context of reduced cholinesterase activity increased jaw pressure (up to 60 s), malignant hyperthermia Rocuro­ For RSI: 1.0 – 1.2 mg/kg BW IV Non-depolarising Tachycardia, injection pain, Reversible using sugammadex nium For geriatric patients use neuromuscular blocking allergic reactions physically incompatible with 0.6 mg/kg BW IV (Duration of agent with an intermediate dexamethasone, diazepam, action can be prolonged) duration of action furosemide, hydrocortisone sodium Onset of action: 60 – 120 s Competitive effect on the succinate, insulin, intralipid, nicotinic acetylcholine methylprednisolone, prednisolone Duration of action: 30 – 67 min (ACH) receptor at the motor sodium succinate, thiopental end plate

tenance of anaesthesia via repeat bolus should be taken into account especially head injuries on the condition that nor­- administration during transfer to hospi- when treating geriatric patients. moventilation is monitored using cap- tal. It exhibits amnestic and anticonvul- Sufentanil: with regard to opioids com­ nography. sive effects. monly used in emergency medicine Neuromuscular blocking agents Thiopental: this drug is made available sufentanil exhibits the greatest affinity For RSI neuromuscular blocking agents as a powder for solution by some EMS to µ receptors but – like fentanyl – is not with a rapid onset of action are essen- (Table 7). As a barbiturate it exhibits a approved for use as an analgesic outside tial (Table 9) – it is for this reason that rapid onset of action, good suppression the setting of general anaesthesia (Table rocuronium and succinylcholine are suit­- of reflexes and depth of anaesthesia, 8). It can be bolused or administered able for use in emergency medi­cine. and anticonvulsive effects in addition to continuously via syringe driver. reducing intracranial pressure. As such Succinylcholine distinguishes itself from Ketamine/esketamine: depending on it is particularly suited to induction of rocuronium through its more rapid onset dose administered, ketamine and eske­t­- anaesthesia in head injuries, intracranial and significantly shorter duration of amine can be used as analgesics or for haemorrhage and status epilepticus. Its action. Its side effect profile and contra­ induction and maintenance of anaes- side effects are hypotension (so provide indications (hyperkalaemia, contraindi- thesia. Low doses lead to dissociative fluid management and possibly vaso­ cations: prolonged immobilisation, pos- analgesia (a cataleptic state entailing pressors), liberation of histamine poten­ sible trigger for malignant hyperthermia) amnesia and analgesia) whilst protective tially causing bronchospasm, and wide- have, however, led to more frequent use reflexes and spontaneous breathing are spread necrosis following paravascular of rocuronium in the prehospital setting. sustained depending on dose. Medium administration. Ultimately only neuromuscular block doses cause hypnosis whilst high doses Analgesics also lead to bronchodilation, making can provide optimum conditions for intubation in an emergency setting. Po- Fentanyl: well-established in most EMS, ketamine especially suited to induction tential reversal of neuromuscular block fentanyl can be carefully titrated as of anaesthesia for status asthmaticus. The monotherapy at low doses to provide opioid and NMDA (N-methyl-D-aspar- following a correct decision to induce analgesia whilst maintaining spontane- tate) receptor mediated analgesic effect is anaesthesia is the subject of ongoing ous breathing or in combination with a desirable. Conversely, undesirable states debate. The authors are of the opin- hypnotic for induction and maintenance of arousal and nightmares have been ion, however, that prehospital airway of anaesthesia (Table 8). It is also effec- described (such that benzodiazepines management should instead employ a tive when administered via the nasal or are co-administered), as have hyperacusis strategy of going forwards, providing buccal routes. Its major side effect is and hypersalivation (requiring suction). and using alternative means of airway respiratory depression, something which Ketamine can be used in patients with management. 62 Review Articles Medical Education

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