Airway, Ventilation, and Sedation

Neurocrit Care https://doi.org/10.1007/s12028-019-00812-6

AIRWAY, VENTILATION, AND SEDATION Emergency Neurological Life Support: Airway, Ventilation, and Sedation Asma Moheet1*, Marlina Lovett2, Stephanie Qualls3 and Venkatakrishna Rajajee4*

Abstract Neurocritically ill patients often have evolving processes that threaten the airway and adequate ventilation; as such, airway and respiratory management are of utmost importance. Airway management, intubation, ventilation, and sedative choices directly afect brain physiology and perfusion. Emergency Neurological Life Support topics discussed here include acute airway management, indications for intubation with special attention to hemodynamics and preservation of cerebral blood fow, initiation of mechanical ventilation, and the use of sedative agents based on the patient’s neurological status in the setting of acute neurological injury. Keywords: Airway, Ventilation, Sedation, Neurocritical care, Emergency

Introduction paralyzing medications should be performed to provide Airway management and respiratory support of the a functional baseline whereby neurological and neurosur- acutely brain-injured patient can be a matter of life or gical decision-making may ensue. death. Failure to establish an airway in a patient with Te Emergency Neurological Life Support (ENLS)- rapidly progressive neurological decline may result in suggested algorithm for the initial management of respiratory arrest, acidosis, secondary brain injury from airway, ventilation, and sedation is shown in Fig. 1. Sug- hypoxemia, elevated intracranial pressure, severe aspira- gested items to complete within the frst hour of evalu- tion pneumonitis, acute respiratory distress syndrome ating a patient are shown in Table 1. Tese suggestions (ARDS), and cardiac arrest. Conversely, the process of are meant to give a broad framework for the principles of induction and intubation itself can result in physiologic diagnosis and emergent management of airway, ventila- changes which increase intracranial pressure (ICP) in tion, and sedation, which can be adapted to refect global brain-injured patients, worsen cerebral perfusion in and regional variations based on the local availability of patients with an ischemic penumbra, and result in loss diagnostic tools and treatments. of the neurological examination at a time when it is required for urgent decision-making. Assessing the Need for Intubation Te goals of airway management in neurological Patients in severe respiratory distress or impending res- patients are to maintain adequate oxygenation and ven- piratory or cardiac arrest should be intubated without tilation, optimize cerebral physiology, preserve cerebral delay. Additionally, a patient who cannot “protect their perfusion, and prevent aspiration. A rapid neurological airway” because of progressive neurological decline or assessment prior to the administration of sedating and concern for aspiration may need tracheal intubation. Intubation should not be delayed, but due to the potential *Correspondence: [email protected]; [email protected] for complications such as signifcant hemodynamic dis- 1 Neurocritical Care, OhioHealth - Riverside Methodist Hospital, turbances, a rapid but thorough risk–beneft assessment Columbus, OH, USA should be conducted. Te decision to intubate is infu- 4 Departments of Neurosurgery and Neurology, University of Michigan, Ann Arbor, MI, USA enced by factors specifc to patient physiology, clinical Full list of author information is available at the end of the article environment, and the anticipated course of care. Fig. 1 ENLS airway, ventilation, and sedation protocol

A stuporous, deteriorating, or comatose patient requir- With these considerations in mind, there are four com- ing extended transport, transfer, imaging, or invasive monly accepted indications to intubate: procedures may be most appropriately managed with a secure endotracheal airway. Table 1 Airway, ventilation, and sedation checklist within the frst hour Checklist

□ Assess the need for intubation or noninvasive positive pressure ventilation □ Perform and document a focused neurological assessment prior to intubation □ Verify the endotracheal tube position □ Determine ventilation and oxygenation targets, and verify with ABG/SpO2/ETCO2 □ Assess the need for analgesia and/or sedation in mechanically ventilated patients

ABG arterial blood gas, ETCO2 end-tidal CO2, SpO2 peripheral oxygen saturation

1. Failure to oxygenate is indicated. When spontaneous breathing is absent or seriously impaired, bag mask ventilation (BMV) should Tis fnding may be determined by visual inspection be performed. Airway adjuvants such as a nasal airway or such as evidence of respiratory distress or cyanosis, vital oropharyngeal airway may be used. Te decision to per- signs data such as low oxygen saturation on pulse oxime- form endotracheal intubation in the prehospital setting, try, or laboratory data such as arterial blood gas analysis. however, can be challenging. Prehospital intubation has been best studied in severe traumatic brain injury (TBI). 2. Failure to ventilate Observational studies in the setting of TBI have been inconsistent [5], with some studies demonstrating pos- Ventilation is assessed by visual inspection including sible harm from prehospital intubation [6]. In one study, observation of respiratory efort exerted, capnometry prehospital intubation performed by aeromedical crews through nasal cannula or transcutaneous monitoring [1], with specialized training was associated with improved and/or arterial blood gas analysis. outcomes [7]. An Australian randomized clinical trial of patients with TBI with Glasgow Coma Scale (GCS) ≤ 9 3. Failure to protect the airway and > 10 min of ground transport time to a designated trauma center demonstrated improved 6-month out- Airway protection is the result of numerous variables comes in patients who underwent prehospital intubation including bulbar function, airway anatomy, quantity and [8]. Given these conficting results, and extrapolating quality of secretions, strength of cough refex, and ability to from studies performed in TBI, prehospital intubation swallow after suctioning [2, 3]. Te presence of a gag refex in patients with acute neurological injury should be per- is an inadequate method of assessing airway protection [4]. formed by personnel with appropriate training and experience in Rapid Sequence Intubation (RSI) patients with 4. Anticipated neurological or cardiopulmonary decline GCS < 9, an inability to protect the airway or hypoxemia requiring transport or immediate treatment despite the use of supplemental oxygen. When personnel with appropriate training and experience are not pre- Anticipation of the trajectory of the patient’s condition sent, or an attempted intubation is unsuccessful, BMV can allow for appropriate preparation for the procedure should be performed in conjunction with basic airway- as opposed to rushed or emergent intubations. opening maneuvers or airway adjuncts while the patient is transported to the hospital. Of note, supraglottic airway (SGA) devices may be especially useful under these cir- Prehospital Management cumstances, as an alternative to endotracheal intubation First responders assessing patients with impaired breath- in the prehospital setting, or by persons trained in these ing in the setting of possible underlying neurological devices, but not intubation. Once an endotracheal tube or injury should rapidly assess the scene and provide support SGA has been placed, the use of quantitative capnography for airway and breathing in a safe and expeditious man- should be used when available, to avoid both hypoventila- ner. Patients who sufer acute neurological injury may tion and hyperventilation [1]. demonstrate one of the above criteria for intubation at the time of assessment. Tose with an inability to protect the airway should be managed immediately with an airway- Decision Made to Intubate: Perform Neurological opening maneuver: the jaw-thrust maneuver is preferred Assessment when the cause of the patient’s neurological impairment When circumstances permit, urgent management of is not readily apparent and cervical spine immobilization the airway should coincide with a focused neurological assessment. Te examination can typically be conducted L = Look externally, for features such as abnormal in 3 min or less, as many components of the examination facies, oro-maxillo-facial trauma, and abnormal body rely simply on careful observation of the patient while habitus they are being stabilized. Te pre-sedation/pre-intuba- E = Evaluate with the 3-3-2 rule: tion neurological examination establishes a baseline that is used to assess therapeutic interventions (e.g., patients • Will 3 of the patient’s fngers ft between the inci- with stroke, seizures, hydrocephalus, or other disorders) sors of the open mouth? If not, mouth opening may or may identify injuries that are at risk of progressing be too limited to permit adequate DL or manipula- (e.g., unstable cervical spine fractures). Te assessment tion of the endotracheal tube. identifes the type of testing required and may help to • Will 3 of the patient’s fngers ft between the chin limit unnecessary interventions, such as radiological cer- (mentum) and the hyoid bone? If not, the airway vical spine clearance. Findings should be documented may be too anterior for easy visualization with DL. and communicated directly to the team that assumes care • Will 2 of the patient’s fngers ft between the hyoid of the patient. Te pre-intubation neurological examina- bone and the superior thyroid notch? If not, the tion should include an evaluation of: airway may be too high in the neck to permit easy visualization. •• Level of arousal, interaction, and orientation, as well as assessment of simple cortical functions such as M = Mallampati score assesses the extent of mouth vision, attention, and speech, and comprehension opening in relation to tongue size [14] (Fig. 2). •• Limited cranial nerve evaluation: pupil assessment, Grade I—Soft palate, entire uvula, faucial pillars visible eye movements Grade II—Soft palate, entire uvula visible •• Motor function of each individual extremity Grade III—Soft palate, base of uvula visible •• Tone and refexes Grade IV—Only hard palate visible •• Recognition of involuntary movement consistent with tremor or epileptic activity Grades I and II predict easy visualization, Grade III •• Cervical tenderness or spinal abnormality predicts difculty, and Grade IV extreme difculty. Mal- •• Sensory examination in patients with suspected spi- lampati grading ideally requires some patient coopera- nal cord injury to identify a sensory level tion and may be difcult to assess in patients with acute brain injury. Airway Assessment O = Obstruction/Obesity. Te presence of redundant A difcult airway may be broadly defned as an endotra- soft tissue (obesity), a supraglottic mass, or trauma/ cheal intubation attempt in which a provider who is hematoma within the oropharynx may obscure the view appropriately trained in airway management experi- of the glottis. ences difculty with BMV, tracheal intubation, or both N = Neck mobility. Inability to attain the snifng posi- [9]. Using this broad defnition, up to 30% of emergency tion because of immobilization of the cervical spine in department (ED) intubations may involve “difcult air- the trauma patient, ankylosing spondylitis, rheumatoid ways” [10]. Patients with acute neurological injury may arthritis, or age-related degenerative disease. be at higher risk for a difcult airway because of the need Te “MOANS” pneumonic predicts difculty of bag to immobilize the cervical spine in patients who sufer mask ventilation [13]: trauma or are “found down” following neurological emer- gencies such as strokes or seizures. It is essential that all M = Mask seal may be compromised by abnormal healthcare providers who manage critically ill neurologi- facies, facial hair, and body fuids cal patients be able to identify common factors that may O = Obesity/obstruction increase the complexity of airway management. Iden- A = Age > 55 tifcation of the difcult airway is essential for selection N = No teeth of the appropriate technique (awake fberoptic vs. rapid S = Stif lungs sequence induction) and tools [video vs. direct laryngoscopy (DL)]. Failure to identify a difcult airway prior to When a difcult airway is identifed, the most impor- induction is one of the most important factors predicting tant next step is to ensure the provider with the most a subsequent failed airway during the intubation attempt experience in airway management is present at the bed- [11, 12]. side, as well as a provider capable of rapidly establish- Te “LEMON” pneumonic has been shown to success- ing a surgical (or percutaneous) airway in the event of a fully predict difcult tracheal intubation in the ED [13]: failed intubation. Availability and functional status of all of critically ill patients will develop severe hypoxemia during intubation, 10–25% will develop severe hypotension, and about 2% will sufer cardiac arrest [12, 22, 23]. More so than other critically ill patients, the patient with an acute brain injury is unlikely to tolerate signifcant periods of hypoxemia or hypotension due to the risk of secondary brain injury [24–26]. Te ENLS intubation algorithm (Fig. 3) therefore emphasizes evidence-based best practice for maintenance of adequate oxygenation and perfusion during intubation, as well as the most direct and dependable pathway to a defnitive airway. As a frst step, at least two providers, including at least one provider experienced in airway management, should be present at the bedside. Two-provider presence may decrease complications associated with intubation of the critically ill [22, 27].

Awake Intubation Te provider may be “forced to act” in the patient with acute neurological illness who has a compromised airway and rapid progression to cardiovascular or respiratory collapse, necessitating an urgent attempt at laryngoscopy and intubation. When the provider is not “forced to act,” however, and the patient is spontaneously breathing and oxygenating adequately on supplemental oxygen, consideration should be given frst to an awake intubation. An awake fberoptic intubation will avoid possible displacement of the cervical spine due to use of the laryngoscope [28] and may be the intubation technique of choice in the Fig. 2 Mallampati score assesses the extent of mouth opening in presence of signifcant cervical spine injury. An awake relation to tongue size. From Allen et al. [15] intubation may also be the procedure of choice when an anticipated difcult airway or BMV makes cessation of spontaneous respiratory efort RSI hazardous. Awake necessary tools at the bedside, such as a SGA, endotra- intubation is typically performed using moderate seda- cheal tube introducer (bougie), cricothyroidotomy tray, tion in conjunction with topical anesthesia, most com- and a video laryngoscope, should be confrmed. Finally, monly with a fexible endoscope that is navigated into the it is important to remember that prediction of a dif- trachea via an oral or nasal route [29]. An endotracheal cult airway is imperfect and that an unanticipated dif- tube ftted onto the fexible endoscope is then advanced cult airway may be encountered at any time [16]. Ready over the endoscope into the trachea. An awake intuba- availability of the necessary expertise and equipment in tion is not appropriate in patients with elevated intrac- the form of an institutional airway team may increase ranial pressure, as stimuli are often avoided and deep survival to hospital discharge and decrease the need for a sedatives may be required in this setting. A fberoptic surgical airway [17]. intubation requires considerable expertise and should be performed only with a highly experienced provider at Endotracheal Intubation of the Critically Ill the bedside. Should awake intubation be unsuccessful, Neurological Patient the experienced provider must decide on an alternative Several societies have published guidelines for the man- technique with the greatest likelihood of success and may agement of the difcult airway, particularly in the setting consider video laryngoscopy (VL), a SGA, or a surgical of anesthesia for elective procedures [9, 18–21]. Intu- airway. bation of the critically ill patient is a fundamentally dif- ferent clinical situation than intubation in the relatively Pre‑oxygenation and Apneic Oxygenation stable environment of the operating room [20, 21]. While Maintaining adequate oxygen saturation before and over 90% will be technically successful, about 20–25% during intubation is critical for the patient with acute Fig. 3 Algorithm for tracheal intubation of the critically ill neurological patient

neurological illness. Any signifcant period of hypoxemia suggests that apneic oxygenation increases time to may result in secondary injury to the vulnerable brain desaturation and frst-pass success without hypoxemia and exacerbate ICP elevation [25, 30]. When feasible, [32–35]. Since apneic oxygenation is easy to perform, pre-oxygenation should be performed prior to intuba- inexpensive, and without serious adverse efects, its use is tion. Tree minutes of pre-oxygenation with noninvasive recommended during intubation of the critically ill neu- positive pressure ventilation (NIPPV) [31] or a heated rological patient. high-fow nasal cannula (HHFNC) at 60–70 L/min that is continued following induction may be more efective Intubating the Patient with Intracranial Pathology at preserving oxygenation during the intubation attempt RSI consists of the simultaneous administration of a fast- than pre-oxygenation with a high-fow (non-rebreather) active sedative to induce immediate unresponsiveness face mask. Pre-oxygenation should be performed with and a neuromuscular-blocking agent to achieve optimal the head of bed (HOB) elevated to 30°. intubating conditions, with the goal of attaining control Apneic oxygenation consists of the administration of of the airway in the critically ill patient at risk of aspira- high-fow oxygen via HHFNC at 60–70 L/min or a regu- tion of stomach contents. RSI limits the elevation of ICP lar nasal cannula at 15 L/min after RSI, during laryngos- often associated with the physiologic responses to laryn- copy. While randomized trials have failed to consistently goscopy and is the preferred method for intubation of the demonstrate an improvement in outcomes, the prepon- patient with elevated ICP [36, 37]. Te presence of coma derance of evidence, including four recent meta-analyses, should not justify proceeding without pharmacological agents, or administration of only a neuromuscular-blocking agent without appropriate pre-treatment induction agents. Although the patient may seem unresponsive, laryngoscopy and intubation often provoke refexes that elevate the ICP unless appropriate pre-treatment induction agents are used [38]. Outcomes in brain-injured patients are related to the maintenance of both brain perfusion and oxygenation. It is generally recommended that the ICP be maintained below 23 mmHg, systolic blood pressure (SBP) > 100–110 mmHg, and cerebral perfusion pressure (CPP = MAP–ICP) at a minimum of 60 mmHg during intubation [39]. When the airway is manipulated, two responses may exacerbate intracranial hypertension. Te refex sympathetic response (RSR) results in increased heart rate, increased blood pressure, and in brain-injured patients, increased ICP due to the loss of normal autoregulation. Te direct laryngeal refex stimulates an increase in ICP independent of the RSR [13]. Because the ICP may not be known at the time of urgent intubation, clinicians should anticipate elevated ICP in patients with conditions such as mass lesions, hydrocephalus, or extensive cerebral edema and choose an appropriate BP target accordingly. Elevations in ICP should be mitigated by minimizing airway manipulation by having the most experienced person perform the intubation and administer medications. Two common pre-medications used to prevent Fig. 4 Intubation with elevated ICP [43] increased ICP during intubation are discussed in more detail below.

Lidocaine •• Perform intubation with HOB ≥ 30°. Reverse Tren- delenburg positioning during intubation may be con- Administered intravenously at a dose of 1.5 mg/kg sidered instead for patients who continue to require 60–90 s before intubation, lidocaine attenuates the direct immobilization of the thoraco-lumbar spine. laryngeal refex. Tere is mixed evidence that it mitigates •• MAP must be preserved throughout the procedure, the RSR [40, 41]. It is not associated with drop in mean with a goal of 80–110 mmHg, but not lower than the arterial pressure (MAP). pre-intubation blood pressure. If ICP is monitored, keep CPP > 60 mmHg. Fentanyl •• Pain, discomfort, agitation, and fear must be con- At doses of 2–3 μg/kg, fentanyl attenuates the RSR asso- trolled with adequate analgesia and sedation. ciated with intubation and is administered as a single pre- •• Hypoventilation must be avoided, and quantitative treatment dose over 30–60 s in order to reduce chances end-tidal capnography monitoring is recommended. of apnea or hypoventilation prior to induction and paral- •• Adequate oxygen saturation should be maintained ysis [42]. It is generally not used in patients with incipient at all times during intubation. In addition to the use or actual hypotension, or those who are dependent on of efective pre-oxygenation and apneic oxygenation, sympathetic drive to maintain an adequate blood pres- BMV should be used between intubation attempts sure for cerebral perfusion. and at any time that the peripheral oxygen saturation ICP during intubation also rises due to body position- (SpO 2) is lower than 94%. ing and hypoventilation. Hypoventilation immediately increases the arterial partial pressure of carbon diox- Intubating the Patient with Brain Ischemia ide (PaCO2), a potent acute cerebral vasodilator. When In suspected or proven ischemic stroke, careful atten- ICP is known or suspected to be elevated, the following tion should be taken to avoid hypotension during approach is suggested (Fig. 4): induction and post-intubation. In the healthy state, the cerebrovascular circulation is well collateralized. During for most ischemic stroke patients requiring endovascu- an ischemic stroke, many patients possess an infarct core lar therapy. Intubation should be considered, however, surrounded by a greater region of ischemic penumbra. for patients with bulbar dysfunction, an inability to pro- Under these circumstances, the ischemic penumbra con- tect the airway or control secretions, hypoxemia, hyper- sists of a region of vasodilated vessels, receiving maximal capnia, a high risk of aspiration (including patients with compensatory shunting from the adjacent cerebrovas- emesis), or signifcant agitation [49]. cular circulation. Hypertension and tachycardia often refect a compensatory, not pathophysiologic, response Intubating the Patient with an Unsecured Vascular to this ischemia and may be necessary to maintain perfu- Malformation or Expanding Hematoma sion of the ischemic territory. Laryngoscopy may result in severe hypertension as a con- Certain vasoactive agents may reverse regional vaso- sequence of the RSR. Severe hypertension may increase constriction in normal areas of the brain that is neces- the risk of rebleeding from a ruptured aneurysm or other sary to maintain physiologic shunting of blood to the intracranial vascular malformation [52]. Severe hyper- region of ischemia, even if they do not drop the systemic tension may also result in hematoma expansion following blood pressure or alter the global CPP. An episode of intracerebral hemorrhage [53]. Fentanyl should therefore relative or actual hypotension can dramatically increase be considered for pre-treatment prior to RSI, to blunt the brain infarct size by “stealing” blood fow from the maxi- RSR. In addition, ketamine, which causes sympathetic mally dilated watershed territories between vascular stimulation, should likely be avoided for RSI. Appropriate distributions. analgesia and sedation should be initiated immediately Brain ischemia is not limited to ischemic stroke but is following intubation, to avoid dyssynchrony and hyper- also variably present in patients with vasospasm, TBI, tension from discomfort caused by the presence of the intracranial and extracranial cerebrovascular stenosis, endotracheal tube. and hypoxic–ischemic encephalopathy following resuscitation from cardiac arrest. Strong correlations between episodic hypotension and poor neurological outcome Intubating the Patient with Neuromuscular have been noted in the critical hours following resus- Weakness citation from TBI and cardiac arrest [26, 44–46]. Even Although some patients with neuromuscular disease transient reductions in cerebral blood fow (CBF) may require immediate intubation, those with preserved be harmful, and every efort should be made to main- bulbar function and reasonable functional ventilatory tain CBF and systemic vascular tone during airway man- reserves may undergo a trial of noninvasive ventilation agement. A fuid bolus should be administered prior to combined with airway clearance by the frequent use of intubation in any patient with possible volume depletion. chest physiotherapy and a cough-assist device [54]. Ketamine or etomidate is the preferred induction agents Any patient with neuromuscular weakness that com- in patients with compromised cerebral perfusion. Vaso- plains of dyspnea should undergo an assessment of res- pressors should be administered to prevent hypotension piratory function that includes (see also the ENLS Acute as needed during or following RSI. Brain ischemia is Non-Traumatic Weakness protocol): worsened by the efect of hyperventilation upon vascular tone. Normocapnia should be maintained during intuba- •• Arterial blood gas measurement tion, and early correlation of PaCO2 with end-tidal CO2 •• Serial respiratory function assessments including (ETCO 2) is suggested to enable noninvasive tracking of negative inspiratory force (NIF), forced vital capacity ventilation [1]. (FVC), and/or maximum expiratory force (MEF) Conficting evidence exists regarding the risks of rou- •• Assessment of bulbar function, neck strength, and tine intubation and general anesthesia for acute ischemic cough stroke patients who require endovascular intervention [47–49]. Two randomized trials of conscious sedation Candidates for intubation include patients with bulbar versus intubation in patients undergoing urgent endo- dysfunction and a demonstrated inability to manage air- vascular thrombectomy for acute ischemic stroke did not way secretions or maintain a patent airway, those who show a diference in outcomes; as such, patients should have a rapidly progressive course, and those who do not not be intubated simply because they are undergoing rapidly stabilize gas exchange and work of breathing with urgent thrombectomy with no other indications [50, 51]. noninvasive ventilation [54]. Since there is some evidence to suggest harm from rou- Choice of neuromuscular blockade should be carefully tine use of general anesthesia [47–49], moderate seda- considered in neurocritically ill patients. In myasthenia tion without intubation may be the technique of choice gravis, succinylcholine is safe but requires approximately 2.5 times the dose for the same efect [55]. Non-depolarizing agents such as rocuronium are also safe but will have a prolonged duration [55]. In conditions such as Guillain–Barré, succinylcholine can precipitate life- threatening hyperkalemia, and only non-depolarizing agents should be used.

Intubating the Patient with Cervical Spine Injury Cervical spine injury should be suspected following direct neck trauma or blunt head trauma resulting in loss of consciousness. During care of these patients, meas- ures must be taken to protect the spinal cord during any movements or procedures, including intubation. Certain airway maneuvers can result in displacement of the cervical spine and injury to the spinal cord in the setting of Fig. 5 Manual in-line stabilization during intubation of the patient who requires immobilization of the cervical spine. Image depicts use cervical instability. Tese include head tilt/chin lift, BMV, of video laryngoscopy cricoid pressure, and DL and should be avoided in this patient population [28, 56, 57]. Blade elevation results in the greatest displacement of the spine during laryngos- results in a better view of the glottis than DL [63–65], manipulation of the ETT into the glottis can be challeng- copy [28]. Awake fberoptic intubation should, therefore, ® be considered the best option in patients with signif- ing. When using the Glidescope (Verathon Medical Inc, cant cervical spine injury who are awake, spontaneously Bothell, WA) VL, the hyperangulated rigid stylet should breathing, and have stable oxygenation on supplemental be used. Te anterior part of the semirigid collar should oxygen [58, 59]. Patients with acute hypoxemic or hyper- be promptly re-applied following intubation. capnic respiratory failure and rapid clinical decline may not be suitable candidates for an awake fberoptic intuba- Rapid Sequence Intubation tion; such patients may require RSI with manual in-line Prior to intubation, consider the use of a pre-intubation stabilization (MILS). Similarly, patients who may have checklist (Fig. 6) [12, 21]. raised ICP and those with impending or established cardiovascular collapse should not undergo awake fberop- Induction Agents tic intubation. When RSI is performed, every precaution Since hypotension is common following sedation [12, 22, should be taken to minimize displacement of the cervical 23, 66] and may exacerbate secondary injury in patients spine, although some movement may be inevitable [28, with acute brain injury [24–26, 30, 44, 67], the use of a 56, 57]. Prior to intubation, the anterior part of the semi- hemodynamically neutral agent such as etomidate or rigid collar should be removed to permit greater mouth a sympathetic stimulant such as ketamine is recom- opening during laryngoscopy. Te head should then be mended. Table 2 lists the properties of some medications maintained in the neutral position using MILS (dem- commonly used for RSI in patients with acute neurologi- onstrated in Fig. 5), in which an assistant stands by the cal illness. patient with a hand on either side of the head between the mastoid process and the occiput [56]. Te assistant Etomidate must then hold the head steady while gently opposing the Etomidate is a short-acting agent that provides sedation applied forces of airway manipulation. and muscle relaxation with minimal hemodynamic efect, When a basic maneuver is necessary to open the air- administered at a dose of 0.3 mg/kg intravenous (IV) way, a jaw thrust should be performed rather than a head push. Despite concerns about adrenal suppression, it is tilt/chin lift. Te use of cricoid pressure is no longer rec- considered to be one of the most hemodynamically neu- ommended during intubation. It defnitely should not be tral of all commonly used induction agents and a drug of implemented in patients with cervical spine injury, as it choice for patients with elevated ICP or compromised may cause posterior displacement of the cervical spine cerebral perfusion [68]. [60]. MILS adversely impacts visualization of the glottis, with only the epiglottis visible in about 22% of patients Ketamine intubated using DL [61]. Te use of VL to improve glot- Ketamine is a dissociative agent administered at a dose tic visualization has therefore become common practice of 2 mg/kg IV push. Ketamine causes sympathetic stimu- when MILS is necessary [62]. While VL consistently lation and is therefore the most favorable of all available PATIENT EQUIPMENT TEAM PLAN FOR DIFFICULTY

1. RELIABLE IV/ IO ACCESS 1. MONITORING 1. ASSIGN ROLES 1. CANNOT INTUBATE CAN o SpO2 with volume turned o First intubator VENTILATE 2. OPTIMAL POSITION up Backup intubator 2-3 aempts by o o o o Head of bed- consider 30-45 o Quantave waveform o Bag-mask venlaon experienced operator with elevaon capnography (ETCO2) o Manual in-line stabilizaon apneic oxygenaon as long o Bed height o Electrocardiogram o Drugs as SpO2>95% o Access to airway o Blood pressure- cuff to cycle o Monitoring o Supragloc airway Sniffing/ neutral/ ramped every 2 minutes or arterial o o Documentaon o Invasive airway line. Cuff not on side of o Invasive airway 3. PRE-OXYGENATION SpO2 probe. 2. CANNOT INTUBATE o Heated high flow nasal 2. Who will be called for CANNOT VENTILATE cannula 60-70 L/mt 2. EQUIPMENT backup? o Supragloc airway Noninvasive posive Laryngoscope handle and o o o Emergent Pressure venlaon blades, test bulb Cricothyroidotomy o Reservoir-bag mask o Video laryngoscope, blade o Bag-valve mask and rigid stylet o Endotracheal tube x2 with 4. APNEIC OXYGENATION IN stylet-selected size and PLACE smaller opon 5. Heated high flow nasal o Bougie cannula 60-70 L/mt o Oral/ nasal airway o Nasal cannula 15L/mt o Sucon o CO2 detector 6. OPTIMIZE PATIENT STATE o Supragloc airway o Pre-treat with fentanyl and o Kit for invasive airway lidocaine o Raised intracranial pressure- 3. MEDICATIONS 23.4% NaCL or mannitol o Sedave o Hypotension/ hypovolemia- o Neuromuscular blocking fluid bolus, vasopressors agent infusing o Vasopressor o Le / right ventricular failure- o Sedaon/ analgesia vasopressor available/ following intubaon infusing

Fig. 6 Pre-intubation checklist. Adapted from 4th National Audit Project of the Royal College of Anaesthetists and Difcult Airway Society (NAP4) and Difcult Airway Society Guidelines for the management of tracheal intubation in critically ill adults 2018 [12, 21]

induction agents from a hemodynamic standpoint [69, in patients with severe hypertension, particularly in the 70]. It is the induction agent of choice for patients with context of acute subarachnoid or spontaneous intra- shock or compromised cerebral perfusion. Historically, parenchymal hemorrhage. use of ketamine was avoided in patients with elevated ICP. Some evidence suggests, however, that when con- Neuromuscular Blockade current sedation is provided, it is safe in patients with Succinylcholine elevated ICP [71]. In view of the signifcant sympathetic Succinylcholine is a depolarizing neuromuscular blocker stimulation that accompanies its use, an alternative to with a rapid onset (30–60 s) and short duration of action ketamine should be considered in patients with unse- (5–15 min), making it an ideal agent for RSI. Te RSI cured vascular malformations, acute intracerebral hem- dose is 1.5–2 mg/kg IV. Although it has been associated orrhage, or signifcant ischemic heart disease. with transient increases in ICP, the efect is not considered clinically signifcant [73]. Immobile and chronically Propofol ill neurological patients are at risk for succinylcholine- At a dose of 1.5–2 mg/kg IV push, propofol is an alter- induced hyperkalemia because of an upregulation in native induction agent. However, it is also a potent vas- extra-junctional acetylcholine receptors. Tis includes odilator that may cause hypotension and may not be patients with chronic neurological/neuromuscular dis- appropriate for patients with threatened cerebral perfu- ease such as amyotrophic lateral sclerosis, multiple sion unless concurrently administered with a vasopres- sclerosis and chronic myopathies, as well as those with sor agent [72]. Propofol may therefore be most useful as little as 24–72 h of immobility following acute brain Table 2 Medications commonly used in Rapid Sequence Intubation Drug Dose Onset of action Duration of efect Indications Precautions

Fentanyl 2–3 μ/kg IV over 1–2 min Within 2–3 min 30–60 min Pre-induction, blunts ICP rise Respiratory depression, hypotension, rare chest wall rigidity Lidocaine 1.5 mg/kg IV 2–3 min before 45–90 s 10–20 min Pre-induction, blunts ICP rise Avoid if allergic or high-grade intubation heart block if no pacemaker Esmolol 1–2 mg/kg IV 2–10 min 10–30 min Pre-induction, blunts ICP rise Bradycardia, hypotension, increased airway reactivity Etomidate 0.3 mg/kg IV 30–60 s 3–5 min Induction, sedation; good Decreases seizure threshold, in hypotension. Decreases decreases cortisol synthesis; CBF, ICP, preserves CPP avoid in sepsis Propofol 2 mg/kg IV 9–50 s 3–10 min Induction, sedation, reduces Hypotension, myocardial ICP and airway resistance, depression anticonvulsive efects Ketamine 1.5–2 mg/kg IV 1–2 min 5–15 min Induction, analgesia, seda- Catecholamine surge, possible tion, amnesia, broncho- increase in ICP, “re-emer- dilatory efects; good in gence” phenomenon if not hypotension pretreated with benzos Succinylcholine 1.5–2 mg/kg IV 30–60 s 5–15 min Preferred paralytic unless Avoid in hyperkalemia, myo- contraindicated pathy, neuropathy/denerva- tion, history of malignant hyperthermia Rocuronium 1.2 mg/kg 45–60 s 45–70 min Paralysis when succinylcho- Caution in difcult mask venti- line contraindicated lation and difcult intubation Vecuronium 0.2 mg/kg Within 3 min 35 min Least preferred paralytic This dose speeds onset during for RSI RSI. Caution in difcult mask ventilation and difcult intubation

CBF cerebral blood fow, CPP cerebral perfusion pressure, ICP increase intracranial pressure, RSI Rapid Sequence Intubation or spinal cord injury [74]. It is critical, therefore, that is common and can be utilized in clinical situations the provider performing RSI always screens for con- where a rapid return of muscle function is desirable. traindications to succinylcholine in patients with acute neurological illness, to avoid precipitating a life-threat- Bag Ventilation and Basic Airway Management ening bradyarrhythmia, ventricular arrhythmia, or car- Following induction and paralysis, the use of BMV prior diac arrest. Succinylcholine should be avoided in these to laryngoscopy may improve oxygenation during intuba- patients and a non-depolarizing agent used [75]. tion. While there has been concern about an increased risk of aspiration with routine BMV, the recent PreVent randomized clinical trial of 401 critically ill patients Non‑depolarizing Agents demonstrated that routine BMV following induction Non-depolarizing agents have a longer duration of action decreased the incidence of severe hypoxemia with no than succinylcholine. A non-depolarizing agent with increase in aspiration [78]. Te use of proper BMV tech- rapid onset and relatively short duration of action should nique is critical. Two-provider BMV is preferable, with be used, such as rocuronium (at 1.2–1.4 mg/kg IV push) one provider entirely focused on attaining an efective or vecuronium (at 0.1–0.2 mg/kg IV push). Rocuronium mask seal while simultaneously performing a basic air- produces optimal intubating conditions almost as quickly way-opening maneuver, such as the head tilt/chin lift, or, (45–60 s) as succinylcholine but has a signifcantly longer when cervical spine immobilization is necessary, a jaw duration of action (45–70 min). Te novel agent sugam- thrust (Fig. 7). A second individual performs bag ventila- madex, administered at a dose of 16 mg/kg 3 min fol- tion, and a third provides MILS when necessary. A breath lowing rocuronium dosing, can reverse neuromuscular should be administered approximately every 6 s, using blockade and restore muscle function faster than with the minimum volume required to attain chest rise, along the use of succinylcholine [76, 77]. Sugammadex should with an expiratory–port valve that provides 5–10 cmH2O therefore be available at locations where the use of steroi- of positive end-expiratory pressure (PEEP) [78]. Te rou- dal neuromuscular-blocking agents such as rocuronium tine use of an adjuvant such as an oral or nasal airway may greatly facilitate efective BMV. Apneic oxygenation Fig. 7 Technique of two-provider bag mask ventilation, with a third provider performing MILS. A frst provider grasps the mask with the thumb and index fnger in a “C” hold while the other three fngers grasp the mandible in an “E” hold, while performing either jaw thrust, as shown in this patient, or a head tilt/chin lift. A third provider provides MILS

Fig. 8 Cormack–Lehane laryngoscopic grade. From Chakravarthy and Seipp [84] with a HHFNC or a regular nasal cannula at 15 L/min should be performed following induction and continued during BMV and laryngoscopy. ETT past the sharp curve of the VL blade to the glottis [82]. Te Cormack–Lehane system is used to grade the Laryngoscopy and Intubation direct laryngoscopic view of the glottis [83] (Fig. 8). When BMV is efective, up to three attempts at laryngoscopy and intubation are permissible, as long as Grade I—Entire glottis visible the SpO2 remains > 94%. BMV should be performed Grade IIa—Partial view of the glottis between attempts, and apneic oxygenation continued Grade IIb—Only the posterior extremity of the glottis at all times. With every subsequent attempt, a change (or only arytenoids) visible in operator (more experienced operator steps in) and/ Grade III—Only epiglottis visible, no view of glottis or technique (such as a change from DL to VL, or use inlet of a bougie) should occur. When BMV using optimal Grade IV—Neither epiglottis nor glottis visible technique is inefective, an experienced operator may make a single attempt at laryngoscopy and intubation. Documentation of the direct laryngoscopic grade in the Use of VL should be considered for this “single, best medical record is critical, to inform future airway man- attempt” for optimal glottis visualization. Te use of agement decisions. VL consistently results in higher rates of glottis visualization [63–65] and may be particularly valuable for The Failed Airway less experienced operators and for difcult airways [63, A failed airway is considered to exist in one of the two 79]. Although randomized trials have not consistently situations: (1) the “cannot intubate, cannot ventilate” sce- demonstrated superiority in outcomes with the use of nario, when BMV is inefective at achieving gas exchange VL in the critically ill [79–81], a recent Cochrane meta- and a “single, best attempt” at intubation by an expe- analysis of 64 clinical trials suggested that the use of VL rienced operator is unsuccessful, and (2) the “cannot improves glottic visualization and decreases the num- intubate, CAN ventilate” scenario, when three attempts ber of failed intubations, particularly in patients with at intubation (at least one by an experienced operator) difcult airways [79]. When intubation is performed using best equipment (including VL) and technique have with the Glidescope® (Verathon Medical Inc, Bothell, been unsuccessful, but BMV remains efective. Since WA) VL, use of the hyperangulated rigid Glidescope® both these scenarios may result in death or devastating stylet is recommended, to facilitate navigation of the anoxic injury [11, 12], every provider who participates in airway management of the critically ill neurological •• Normalization of ventilation to achieve a systemic patient must have a basic knowledge of the approach to pH of 7.35–7.45, and PaCO2 to 35–45 mmHg (4.7– a failed airway. In order to provide the most direct and 6.0 kPa) or ETCO 2 that corresponds to PaCO2 target dependable path to a defnitive airway, the ENLS intuba- •• Normalization of the work of breathing tion algorithm recommends an attempt at placement of •• Prevention of ventilator-induced lung injury a SGA, such as a laryngeal mask airway, in the event of a failed airway. SGAs have a high success rate with inex- In most circumstances, clinicians should default to vol- perienced providers and typically require limited training ume-cycled ventilation at 6–8 cc/kg of ideal body weight to use [85, 86]. Te second-generation SGAs that include and a respiratory rate of 12–14 per minute. However, features such as a bite block and an esophageal/gastric these settings must take into account the patient’s min- channel, or SGAs that can serve as conduits for subse- ute ventilation prior to intubation. Normal PaCO2 range quent blind or fberoptic-guided passage of an ETT, are is an appropriate target unless there is chronic hypercap- preferable [87]. Up to two attempts, with diferent opera- nia (i.e., severe chronic obstructive pulmonary disease tors and/or techniques, are permissible as long as the or sleep-disordered breathing). In situations of chronic SpO 2 remains > 94%. Apneic oxygenation should be con- hypercapnia, the admission bicarbonate level should tinued and BMV performed between attempts. If SGA be used to estimate the “baseline” PaCO2, and that level placement is successful and gas exchange established, should subsequently be used as the target. When meta- insertion of an ETT through the SGA may be attempted. bolic acidosis is present, ventilation should target a nor- When SGA insertion is unsuccessful, or oxygen desatu- mal serum pH. ration occurs at any time, immediate cricothyroidotomy should be performed using a surgical or percutaneous Ventilator Modes and Settings technique. Delays in performing a cricothyroidotomy in Te initial ventilator mode should provide a set respira- patients with a failed airway are an important cause of tory rate, while permitting patient initiation of respira- death and severe morbidity [11, 12]. tion (triggered breaths). Assist-control (AC) ventilation Post‑intubation Management and synchronized intermittent mandatory ventilation (SIMV) are the most widely used modes in patients who Following intubation, consider the use of a post-intuba- require substantial ventilator support. AC results in ste- tion checklist (Table 3) [88]. reotypical breaths generated regardless of initiation Basic Ventilator Settings by machine or patient. With SIMV, breaths delivered within the set rate refect the defned parameters, while Immediately following intubation, respiratory and hemo- patient-initiated breaths above the set rate refect either dynamic homeostasis should be restored. Except in situ- patient efort alone, or a level of pressure support that ations of acute brain herniation, the goals of mechanical is added to SIMV (typically about 10 cmH2O). Te set ventilation are: rate is adjusted to achieve the goal PaCO 2, while maintaining the goal ratio of inspiratory to expiratory time •• Normalization of oxygenation utilizing the lowest (I:E ratio) to avoid gas trapping. Most commonly, a fow fraction of inspired oxygen (FiO2) that will maintain trigger is used to detect patient inspiratory efort, set at oxygen saturation of hemoglobin > 94% about 2 L/min. Regardless of mode, breaths delivered may be defned by volume (fow targeted, volume cycled) in which tidal volume is assured, but airway pressures are variable, or by pressure (pressure targeted, time cycled) in which maximum airway pressure is assured, but tidal volume depends on airway resistance and patient efort. Table 3 Post-intubation checklist Volume-control (VC) ventilation is most commonly uti- Post-intubation checklist lized, given the importance of avoiding excessive tidal volumes, particularly in the setting of the ARDS [89]. □ Secure endotracheal tube With VC ventilation, a peak inspiratory fow rate (about □ Confrm tube position, order chest x-ray 60 L/min, titrated to goal I:E ratio and airway pressure), □ Set cuf pressure to 20–30 cmH2O fow pattern (typically a square waveform although □ Pulse oximetry and quantitative waveform capnography ramp and sinusoidal waveforms may also be used), and □ Arterial blood gas measurement tidal volume (typically 6–8 cc/kg) are specifed. Using □ Deep sedation while neuromuscular blockade in efect lower tidal volumes (4–8 cc/kg) is particularly impor- □ Counsel next of kin on change in patient status tant for patients with ARDS [89]. With pressure control (PC) ventilation, an inspiratory pressure (Pi, starting at present when performing an inspiratory or expiratory 8–10 cmH2O and titrated to the goal tidal volume) and hold, measurement of plateau and driving pressure in inspiratory time (Ti, titrated to the desired I:E ratio) are spontaneously breathing patients may be feasible [90]. specifed. A specifc mode of PC ventilation that permits constant auto-titration of Pi by the ventilator to achieve a set tidal volume is frequently used and combines bene- PEEP and Brain Injury fts of PC and VC ventilation. Tis mode may be referred A theoretical concern in patients with acute brain injury to as “Pressure-Regulated Volume Control” (Siemens), is that higher levels of PEEP will increase intrathoracic “VC+” (Puritan Bennett), or “Auto-fow” (Drager), pressure, impair venous return from the brain, and among others. In all cases, FiO2 and PEEP are specifed. worsen elevated ICP. Most studies of applied PEEP up Te FiO2 is usually set at 100% following intubation and to 15–20 cmH2O [91, 92], as well as ventilator modes then titrated to an oxygenation goal. Te PEEP is most such as APRV [93], in the setting of acute brain injury commonly set at 5 cmH2O and is also titrated to an oxy- have demonstrated modest or no impact on ICP. In genation goal to permit reduction of the FiO2 to < 60%. A the setting of ARDS, applied PEEP appears to improve higher initial PEEP may be set in patients with hypoxemia brain tissue oxygenation [94]. A PEEP-induced drop in prior to intubation (particularly those with ARDS) as well cardiac output may, however, compromise cerebral per- as patients with morbid obesity. Airway pressure release fusion [92]. Higher levels of PEEP (> 10 cmH2O) and ventilation (APRV) is a form of extreme inverse ratio PC APRV can, therefore, be used as otherwise appropriate ventilation used in patients with severe acute hypoxic in the setting of acute brain injury, in conjunction with respiratory failure and ARDS. In APRV, the presence of continuous monitoring of ICP and CPP, as well as brain a dynamic expiratory valve in the circuit allows sponta- tissue oxygenation where available. neous breathing at high lung volumes, thereby improv- ing patient comfort while achieving high mean airway pressures to maintain an “open lung.” Pressure support Titrate Ventilation ventilation (PSV) is a weaning mode without a set rate, Induced Hyperventilation: Ventilation, Carbon Dioxide in which all breaths are spontaneous and supported by a Tension, and Clinical Outcome defned level of pressure (often starting at 10–15cmH2O). Hyperventilation causes cerebral vasoconstriction and PSV is used when the patient is on minimal sedation, and decreased CBF, while hypoventilation causes cerebral ventilatory requirements have substantially decreased. vasodilation and increased ICP [95]. Dysventilation Unlike PC, breaths in PSV are pressure targeted but fow (and especially hyperventilation) is associated with poor cycled (with breaths cycled of most commonly at 25% of outcomes in TBI [96–98]. However, the relationship peak inspiratory fow), which makes this the most com- between arterial and central pH and PaCO 2 is complex fortable ventilator mode for most patients. Patients with and incompletely understood. During concomitant meta- neurological injury intubated for airway protection alone, bolic acidosis and TBI, central nervous system (CNS) pH with low requirements of sedation and ventilatory sup- and CBF are often preserved despite severe systemic aci- port, may therefore beneft from PSV. While peak airway dosis due to the blood brain barrier and the CNS bufer- pressures are generally maintained < 30–40 cmH2O, the ing capacity [99]. Alternatively, in patients with chronic pressure parameter that best refects the risk of baro- respiratory acidosis, the set point of cerebral CO2 reactiv- trauma at the alveolar level is the plateau pressure, meas- ity changes. It is therefore recommended that mechani- ured using an inspiratory hold. Te plateau pressure must cal ventilation be adjusted to correct the pH and not the be maintained < 30 cmH2O. Gas trapping (auto-PEEP) PaCO 2 or that the estimated “pre-morbid” PaCO2 target is measured with an expiratory hold, which is used to be used (see Table 4 below). Tis is a practical goal since determine a total PEEP. Intrinsic (auto-) PEEP is then cal- ventilating these patients to “normal” PaCO2 targets may culated by subtracting the applied PEEP. While typically be extremely difcult or impossible when obstructive minimal or no spontaneous respiratory efort should be lung disease is present.

Table 4 Chronic respiratory acidosis: estimated pre-morbid PaCO2 based on admission HCO3 level Chronic respiratory acidosis: Estimated pre-morbid pCO2 based on admission HCO 3 level

Admission bicarbonate (mEq/L) 45 42 39 36 33 30 27 24

Predicted “usual” PaCO2 in mmHg (kPa) 92.5 (12.3) 85 (11.3) 77.5 (10.3) 70 (9.3) 62.5 (8.3) 55 (7.3) 47.5 (6.3) 40 (5.3)

HCO3 bicarbonate, PaCO2 partial pressure of carbon dioxide Herniation: Intentional Hyperventilation to Treat Brain •• Brain tissue acidosis requiring acute hyperventilation Herniation and Increased ICP as a bufer until CNS bicarbonate-generating com- When a patient develops brain herniation with elevated pensatory mechanisms can catch up intracranial pressure, hyperventilation is an appropriate •• Inadequately treated pain, anxiety, fear, or agitation temporizing intervention designed to acutely decrease •• Fever ICP and prevent subsequent neuronal injury and death •• Autoregulation of elevated ICP [100, 101]. Maximal cerebral vasoconstriction is achieved •• Heme breakdown products or a lactic acid load in the at a PaCO 2 near 20 mmHg (2.7 kPa). Terefore, hyper- ventricular system ventilation below this level results in no further therapeu- •• Direct pressure on chemoreceptors present in the tic advantage and even less profound PaCO2 reductions foor of the fourth ventricle may impede venous return to the heart, decrease blood •• Physiologic dysregulation of the medullary respira- pressure, and exacerbate cerebral hypoperfusion. Dur- tory rhythm generator, which has aferent inputs ing hyperventilation, ETCO 2 monitoring (quantitative from the pons, mesencephalon, and higher cortical capnography) is suggested. As soon as other treatments centers to control ICP are in place (e.g., blood pressure support, osmotherapy, surgical decompression, hypothermia, A recent trial of patients with severe brain injury metabolic therapy), hyperventilation should be weaned monitored for brain tissue oxygen showed brain tissue to restore brain perfusion [102]. Hyperventilation hypoxia worsened when ETCO 2 values were reduced by severely reduces CBF, increases the volume of ischemic spontaneous alkalemic hyperventilation, suggesting pos- tissue, and may result in rebound elevation of ICP during sible harm [105]. It is rarely known whether alkalemic weaning [103, 104]. Prolonged hyperventilation (beyond hypocapnia is a physiologic or pathophysiologic process, a few hours) should therefore not be used. suppression of this respiratory activity is recommended only in response to evidence that hyperventilation is causing direct harm, either by inducing cerebral ischemia Acidemic and Alkalemic Hypocapnia: Potential or indirectly by increased systemic metabolic demands for Suppression of Spontaneous Hyperventilation and work of breathing. Tere are two circumstances that should be considered in patients with spontaneous hypocapnia: those whose Oxygenation and Outcomes response to systemic metabolic acidosis accounts for Hypoxemia is a major source of secondary brain injury their high ventilatory demand, and those (alkalotic) [106], and the injured and ischemic brain is particularly patients in whom ventilation exceeds systemic metabolic vulnerable to low oxygen levels. Similarly, supra-physio- needs. logic levels of oxygen provided to acutely ill patients have In patients whose ventilation is driven by metabolic the potential to worsen reperfusion injury and outcomes acidosis, suppression of the respiratory drive with seda- [107, 108]. Hyperoxemia drives the formation of reactive tion or neuromuscular blockade is not recommended, oxygen species, overwhelming antioxidants at sites of unless direct measurement of brain chemistry suggests tissue injury; directly injures respiratory epithelium and that hyperventilation is driving cerebral metabolic crisis. alveoli inducing infammation; drives hypercapnia; and Under these circumstances, clinicians must fnd another leads to absorption atelectasis in the lung. Hyperoxemia means to bufer pH. (PaO2 > 300 mmHg or 40 kPa) immediately following Mechanically ventilated TBI patients presenting with resuscitation is independently associated with poor out- hypocapnia have worse outcomes than their normocap- comes in TBI and cardiac arrest [108, 109], though not all nic peers. However, non-intubated patients presenting published data are concordant [110–112]. with hypocapnia do not exhibit similar fndings, suggest- It is recommended that 100% oxygen be provided for ing that hypocapnia, in this setting, may be a physiologic pre-oxygenation immediately prior to intubation, but response and should not be suppressed [97]. Despite that oxygen be immediately weaned following intubation decades of observation and consideration, little is known to 50%, or the lowest FiO2 that will support an oxyhemo- about alkalemic hypocapnia in patients with an acute globin saturation of 95–100%. brain injury. Alkalemic hypocapnia following brain injury may be theoretically explained by a variety of physiologic Oxygenation and Ventilation Monitoring and pathophysiologic mechanisms, more than one of Oxygenation should be monitored by pulse oximetry which may be present in an individual patient: or by arterial blood gas analysis when oximetry is suspected to be inaccurate. Conditions of poor perfusion to the extremities, acidosis, vasopressor use, anemia, carboxyhemoglobinemia and methemoglobinemia, and beyond their intended duration. Despite each of the com- hypoxia all have the potential to compromise the accu- peting interests, adequate consideration must be made racy of pulse oximetry measurements [113]. for patient comfort and safety. Ventilation is traditionally monitored by serial arterial blood gas analysis, though venous blood gas analysis Depth of Sedation may provide an adequate surrogate when arterial samples In a general intensive care unit (ICU) population, the cannot be obtained. End-tidal quantitative capnography use of excessive sedation and analgesia contributes to of exhaled gases provides an appealing continuous meas- increased duration of mechanical ventilation and longer urement and is extremely useful to monitor trends in ven- length of stay in the ICU and hospital [121, 122]. Tere- tilation. One study showed that severely hyperventilated fore, while some patients with acute neurological illness head trauma patients (PaCO2 < 25 mmHg or 3.3 kPa) in will require deep sedation for the control of ICP or the the prehospital environment had higher mortality and management of status epilepticus, most patients should that use of quantitative capnography by paramedics sig- be lightly sedated, so they are easily arousable and attend nifcantly decreased the incidence of hyperventilation to voice, to the extent their neurological injury permits. [114]. A similar study in patients with major trauma Sedation should be titrated to a validated sedation score showed a much higher incidence of normocapnia on hos- (Table 5), such as the Richmond Agitation–Sedation pital arrival when ETCO 2 was monitored by medics. Scale (RASS) [123, 124], or the Riker Sedation–Agitation Because ETCO 2 measurements refect not only ventila- Scale (SAS) [125]. A recent review of sedation assess- tion but also systemic perfusion, the correlation between ment tools in the neurocritical care setting concluded ETCO 2 and PaCO2 in the blood is variable, especially that the SAS and RASS are valid and useful for patients in when severe physiologic derangements are present [115]. the neurocritical care unit (NCCU) [126]. A goal of light In an inpatient environment, ETCO 2 measurements sedation (approximately a RASS score of 0 to − 2) is rec- should always be correlated with an arterial PaCO 2 sam- ommended for most patients without a specifc indica- ple. ETCO2 and PaCO2 may also vary signifcantly when tion for deep sedation [127]. Sedation should be titrated lung disease and ventilation–perfusion mismatch are to an electrophysiologic endpoint when neuromuscular present [116]. blockade is employed or burst suppression on electroen- cephalography (EEG) is desired. Sedation Necessity of Sedation Role of Analgesics Te use of sedation in the critically ill neurological Unless deep sedation or general anesthesia is desired, patient has both benefts and drawbacks. Sedation may analgesia should precede sedation. Many patients with be needed to alleviate fear and anxiety, reduce ICP and adequate pain control do not require sedation, and con- cerebral oxygen consumption, facilitate tolerance of the versely, most sedative medications provide no analgesia. endotracheal tube and mechanical ventilation, or reduce Sedation without pain control may be an important cause sympathetic hyperactivity. Complications associated with of delirium. Infusion of short-acting analgesics allows for under-sedation include ventilator, patient injury, agita- interruption and neurological assessment at intervals. tion, anxiety, device removal, and elevated ICP. Adequate Recent studies have demonstrated that analgosedation, a sedation is paramount in all therapeutic algorithms for strategy that focuses on using a short-acting opioid infu- the treatment of increased ICP [117, 118], since psy- sion (remifentanil or fentanyl) alone to manage pain and chomotor restlessness, pain, and autonomic stress all discomfort, without a sedative, may result in a reduction adversely afect ICP, CBF, CPP, and the cerebral meta- in duration of mechanical ventilation and ICU length of bolic rate for oxygen metabolism (CMRO 2). Conversely, stay [128–130]. Te use of analgosedation should there- sedation makes accurate neurological examination, the fore be considered frst in all mechanically ventilated cornerstone of clinical assessment, difcult or impos- patients who do not have a specifc indication for a seda- sible. Terapeutic and procedural decision-making are tive infusion, such as raised ICP, seizures, or ongoing use often contingent upon an accurate neurological assess- of neuromuscular blockade [127]. ment. Acute changes in brain physiology become difcult to detect, and the accuracy of neuroprognostication Choice of Sedative is decreased [119, 120]. Sedation may cause vasodila- Patients may require sedation despite the efective use tion, reducing cerebral perfusion due to hypotension and of analgesia within the frst hours following intubation. also reversing physiologically advantageous shunting of Several randomized trials have compared the use of ben- blood into areas of ischemia. Even short-acting sedatives zodiazepine infusions, mostly midazolam, to propofol are known to accumulate in fatty tissues, causing efects and dexmedetomidine. A meta-analysis of these studies, Table 5 Richmond Agitation–Sedation Scale (RASS) the Riker Sedation–Agitation Scale (SAS) Richmond Agitation–Sedation Scale (RASS) Score Term Description

4 Combative Overtly combative or violent; immediate danger to staf + 3 Very agitated Pulls on or removes tube(s) or catheter(s) or has aggressive behavior toward staf + 2 Agitated Frequent, non-purposeful movement or patient–ventilator dyssynchrony + 1 Restless Anxious or apprehensive but movements not aggressive or vigorous + 0 Alert and calm 1 Drowsy Not fully alert, but has sustained (more than 10 s) awakening, with eye contact, to voice − 2 Light sedation Briefy (less than 10 s) awakens with eye contact to voice − 3 Moderate sedation Any movement (but no eye contact) to voice − 4 Deep sedation No response to voice, but any movement to physical stimulation − 5 Unarousable No response to voice or physical stimulation − Riker Sedation–Agitation Scale (SAS) Score Term Description

7 Dangerous agitation Pulling at endotracheal tube (ETT), trying to remove catheters, climbing over bedrail, striking at staf, thrashing side to side 6 Very agitated Does not calm down despite frequent verbal reminding of limits, requires physical restraints, biting ETT 5 Agitated Anxious or mildly agitated, attempting to sit up, calms down to verbal instructions 4 Calm and cooperative Calm, awakens easily, follows commands 3 Sedated Difcult to arouse, awakens to verbal stimuli or gentle shaking but drifts of again, follows simple commands 2 Very sedated Arouses to physical stimuli but does not communicate or follow commands, may move spontaneously 1 Unarousable Minimal or no response to noxious stimuli, does not communicate or follow commands

mostly conducted in general ICU patients, suggests that syndrome. Tis syndrome is characterized by acidosis, both propofol and dexmedetomidine are associated with hepatic failure, hypertriglyceridemia, and elevated cre- shorter ICU length of stay and duration of mechanical atine kinase level. Propofol infusion syndrome may be ventilation compared to benzodiazepine infusions [127]. fatal and is more common in children and adults when Tis is relevant because the agent that is initiated in the used at higher doses [131]. A recent study, comparing early hours for the management of intubation-related dis- propofol to dexmedetomidine sedation in critically ill comfort is typically continued in the ICU. Either dexme- neurological patients, found high (30%) incidences of detomidine or propofol should be utilized as a frst-line hypotension in both groups [132]. Caution must be uti- agent for continuous sedation, rather than a benzodiaz- lized with these medications when concerns for brain epine [127]. ischemia are present.

Common Sedatives in Neurological Intensive Care Propofol Fentanyl Propofol is among the best studied sedative agents used Fentanyl is an opioid agonist exhibiting analgesic efects in neurological critical care. Pharmacologically, its lipid with a rapid onset and a short duration of action. It is an formulation allows for rapid penetration of the blood agent which can be used as part of a combined sedative brain barrier, resulting in rapid onset and cessation of analgesic approach. action. It has potent and immediate depressant efects on cerebral electrical and metabolic activity, and it does Benzodiazepines not require renal or hepatic metabolism for elimination. Disadvantages include robust vasodilating and hypoten- Midazolam is an appealing sedative option given the sive efects, considerable IV lipid load, and the poten- rapid onset of action and short duration of efect with tial for the rare, but frequently fatal, propofol infusion bolus administration, making it an ideal agent for procedural sedation. Bolus-dose midazolam is a good choice for intermittent direct visualization studies have questioned this descrip- agitation in a NCCU population. Conversely, midazolam tion and have suggested more of an elliptical appearance, infusion has been associated with prolonged mechanical with uncertain clinical signifcance [137]. Te infant’s ventilation [132, 133]. Tough most studies suggest the larynx is more anterior and cephalad (C3-4 vs. C5-6 in impact of midazolam on hemodynamics is similar com- adults), so positioning may be optimized by placing a pared to dexmedetomidine or propofol, a recent report small shoulder roll or padding beneath the infant’s torso suggests less instability compared to dexmedetomidine to promote neutral positioning prior to intubation. Pro- [132]. viders should be aware that infants and young children have higher oxygen consumption and are therefore sus- Dexmedetomidine ceptible to hypoxia, have less physiologic reserve than Dexmedetomidine is a centrally acting alpha agonist adults, are more likely to have oxygen desaturation similar to clonidine, but more specifc for the alpha-2 earlier, and have an enhanced vagal response. Pediat- receptor. It is increasingly utilized for ICU sedation. ric Advanced Life Support Guidelines advise that oral Desirable properties include rapid onset and termination intubation, following pre-oxygenation, should be per- of activity, mild to moderate sedation without signifcant formed while maintaining spine immobilization using respiratory depressant action, analgesic efects, and less a cufed endotracheal tube in children with TBI [138, delirium than the benzodiazepines [132, 134]. Undesir- 139]. Length-based resuscitation tapes are helpful when able properties include a high incidence of bradycardia choosing appropriate intubation equipment for the child, and hypotension [132, 134]. including blade and endotracheal tube sizes. If a length- based resuscitation tape is unavailable, the appropriate sized un-cufed endotracheal tube (if cufed is not avail- Pediatric Considerations able) for a child can be calculated using the age-based Anatomical and physiologic diferences alter the formula: 4 + (age in years/4) [140–142]. When using approach to endotracheal intubation and mechanical a regular cufed endotracheal tube, select one full size ventilation of children with neurological injury. While smaller than determined by the age-based formula [119]. isolated cervical spinal injury is uncommon in chil- When using a micro-cufed endotracheal tube, select dren, approximately half of all cervical spinal injuries a tube one half size smaller than the age-based calcula- are associated with concomitant TBI [135]. Terefore, tion for un-cufed tubes [140–142]. Cuf pressures should cervical spine precautions should be taken when intu- be monitored and limited according to manufacturer’s bating the trachea of a child with suspected TBI. Crite- recommendations (usually less than 20–25 cmH2O). A ria for endotracheal intubation of children with TBI and multicenter, randomized control trial demonstrated no other forms of acute brain injury include hypoxemia increase in post-extubation stridor or long-term compli- unresponsive to supplemental oxygen, apnea, hyper- cations when using cufed tubes [143]. capnia (PaCO2 > 45 mmHg or 6 kPa), GCS score ≤ 8 (a When intubating the trachea of a child less than 2 years pediatric version is recommended for children younger old, a straight laryngoscope blade directly lifting the epi- than 4 years of age), rapid decrease in GCS, anisocoria glottis may be preferable because of the infant’s large and > 1 mm in the context of altered mental status, cervical acutely angled epiglottis. A straight size 00 laryngoscope spinal injury compromising ventilation, abnormal airway blade is appropriate for extremely premature infants, refexes, and any clinical signs of herniation or impending size 0 for average-sized newborns, size 1 for most infants herniation [136]. beyond the immediate newborn period, and size 2 for Anatomical diferences between the pediatric and adult children over the age of two. For older children, either a airways that should be considered prior to intubation curved or straight blade may be used. VL is an option for of the trachea include the following: (1) children have a infants and young children and may be used in the set- proportionally larger tongue, (2) upper airway tissues are ting of a difcult airway or associated facial trauma. For more compliant, (3) the epiglottis is longer, narrower, and the child with an anticipated difcult airway, a contin- foppier, (4) the tracheal distance is shorter, and (5) chil- gency plan involving an advanced airway expert should dren have a prominent occiput. Te narrowest portion be available for backup. If an appropriately sized endotra- of the child’s upper airway is subglottic, at the level of cheal tube is placed, the ideal depth can be achieved by the cricoid ring. Historically, the child’s airway has been inserting the tube until the centimeter marking at the lip described as conical in appearance, in contrast to the is three times the endotracheal tube size [144]. adult’s cylindrical airway. However, recent imaging and It is prudent to assume a full stomach and a cervical Table 6 Airway, ventilation, and sedation communication spinal injury when intubating the trachea of a child with regarding assessment and referral TBI. Endotracheal intubation should utilize a cerebral- Communication protective rapid sequence induction with pre-oxygena- □ Mental status and neurological examination immediately pre-intubation. Te time to desaturation following pre-oxygenation tion is shorter in apneic infants compared to older children □ Intracerebral hemorrhage (ICH) score, if appropriate (less than 100 s), and a modifed RSI technique with gen- □ Vitals, hemodynamics, and gas exchange pre- and post-intubation tle pressure-limited mask ventilation (10–12 cmH2O) □ Relevant drugs used around intubation and 100% oxygen may be used to avoid hypoxemia [145, □ Technique of intubation, confrmation of tube position 146]. Tis technique may also limit hypercapnia and □ Ease of bag mask ventilation, intubation, and tube passage keeps small airways open without the risk of gastric infa- □ Cormack–Lehane grade, if appropriate tion and related morbidity [147–149]. Cricoid pressure □ Ventilator settings, ventilation, and ETCO2 targets is routinely applied despite questionable evidence that it □ Analgesia and sedation strategy improves clinical outcomes; however, it should be aban- Pending investigations doned if it interferes with intubation or ventilation [148, □ Sample communication: 150, 151]. “Mr. Smith the 52-year-old gentleman with intracerebral hemorrhage Pre-treatment with lidocaine (1.5 mg/kg IV with max required urgent intubation.” dose 100 mg) may be used, but its administration should “His GCS was 6 prior to intubation—would not open eyes to pain, was mute, and would only withdraw to pain on the right; he appeared to be not delay emergent intubation [152]. Atropine (0.02 mg/ left hemiplegic. His right pupil was 5 mm and sluggish, and left pupil kg IV with a single max dose 0.5 mg) is recommended was 3 mm and briskly reactive. Following intubation, his pupils are in children 1 year old or children < 5 years receiving 3 mm and reactive bilaterally.” ≤ “His vitals prior to intubation were BP 220/110, HR 66/m, SpO2 97% on succinylcholine [153]. For hemodynamically unstable 2 L/m nasal cannula. Following intubation, his BP is 130/60, HR 55/m, children, the combination of etomidate (0.2–0.6 mg/kg) SpO2 99% on FiO2 100% and ETCO2 is 32.” and neuromuscular blockade with rocuronium (1 mg/ “We treated with him with lidocaine, fentanyl, and 30 cc of 23.4% NaCL prior to intubation. We used etomidate and rocuronium for RSI.” kg) or vecuronium (0.3 mg/kg) IV is often used. Te “We intubated him with direct laryngoscopy using a Mac 4 blade. Tube association between etomidate and clinically signifcant position was confrmed with a CO2 detector and auscultation.” adrenal insufciency should be considered when select- “Bag mask ventilation was easy, although I did use an oral airway. I had a Grade 2a view without cricoid pressure, and tube passage was easy.” ing optimal medications for intubation. Succinylcholine “We have him on assist control, volume control, with a tidal volume is sometimes avoided because of the risk of malignant of 6 cc/kg, respiratory rate of 24/m, PEEP 5, and FiO2 100%. Our goal hyperthermia, possible ICP elevation, hyperkalemia in ETCO 2 is 30–35, and goal SpO2 is > 94%.” “We started a propofol infusion, titrated to deep sedation because of the the setting of crush injury, and life-threatening complica- herniation syndrome.” tions associated with unknown occult metabolic or neu- “He will be transported to CT now, and the neurosurgeons will likely romuscular disease [154, 155]. Fentanyl (2–4 μg/kg IV) or take him straight to the operating room. We did not have time to get a chest X-ray, but he has equal breath sounds and is ventilating and ketamine (1–2 mg/kg IV) is alternative sedatives. Recent oxygenating well.” pediatric studies show that ketamine does not increase “His wife is with him and has been counseled about his condition”

ICP and may be neuroprotective [70, 156, 157]. If hemo- CT computed tomography, ETCO2 end-tidal CO2, FiO2 fraction of inspired oxygen, dynamically stable, midazolam (0.1–0.2 mg/kg) may be GCS Glasgow Coma Scale, PEEP positive end-expiratory pressure, RSI Rapid Sequence Intubation added to any of the above combinations. After successful intubation, an arterial blood gas should be obtained to confrm a PaO 2 of 90–100 mmHg 161]. However, optimal age-appropriate CPP thresh- (12–13.3 kPa) and a PaCO 2 of 35–45 mmHg (4.7–6 kPa) olds have not been established for TBI and other acute [136]. Unless the child has signs of herniation, hyperven- neurological diagnoses. Furthermore, abnormal cer- tilation (PaCO2 < 35 mmHg or 4.7 kPa) should be avoided ebrovascular autoregulation, which is more common [158]. Adequate blood pressure must always be main- in children less than 4 years old [162], makes establish- tained when administering sedatives to assure adequate ing such thresholds difcult in the absence of advanced CPP. A CPP between 40 and 50 mmHg is recommended neuromonitoring. for children with severe TBI, with infants at the lower Sedative regimens following intubation of the child end of this range and adolescents at the upper end [159]. with acute neurological illness are variable. In chil- Many studies have demonstrated that a CPP ≤ 40 mmHg dren, propofol infusions are often avoided due to the is associated with higher mortality and morbidity [160, concern for propofol infusion syndrome (a potentially Table 7 Critical care pre-transportation checklist—airway, ventilation and sedation Checklist

□ Confrm adequate pulse oximetry and end-tidal CO2; continue SpO2 and ETCO2 monitoring during transport □ Evaluate hemodynamic status, confrm stability for transport, electrocardiogram and blood pressure monitoring during transport □ Focused neurological assessment prior to transport □ Confrm endotracheal tube position and bilateral air entry; confrm depth of insertion of endotracheal tube has not changed □ Confrm endotracheal tube is secured appropriately □ Ambu bag present with appropriate size of mask and positive end-expiratory pressure valve □ Full tank of oxygen (or adequate oxygen for duration of transport) □ Complete oral and endotracheal suctioning prior to transport □ Confrm adequate IV access and appropriate length of tubing (extra long for magnetic resonance imaging) □ If using a transport ventilator: trial ventilator and settings on patient prior to transport □ Confrm emergency medication box available during transport. □ Confrm sedation plan if appropriate, and availability of sedative/analgesia medications □ Designate individuals in charge of bag ventilation, airway, and monitoring of vital signs

ETCO2 end-tidal CO2, SpO2 peripheral oxygen saturation

Table 8 Nursing considerations: airway, ventilation, and sedation Airway

Vigilantly monitor patients with neurological illness, and alert the provider for respiratory failure based on the four major criteria: • failure to oxygenate • failure to ventilate • failure to protect the airway • anticipated neurological or cardiopulmonary decline If concerned that patient obstructing airway due to decreased level of consciousness, consider use of airway adjuncts such as oropharyngeal airway or nasopharyngeal airway [170] Identify and alert airway team to special considerations: elevated intracranial pressure, unstable cervical spine, cerebral ischemia, vascular malformation, neuromuscular weakness Assist with manual in-line stabilization as required Alert the airway team to a potential difcult airway, identifed using LEMON criteria Ensure adequate intravenous access, presence of suction set up, and hemodynamic monitoring, and assist with optimal positioning, pre-oxygenation, and preparation of medications for induction and neuromuscular blockade [170] Rapid Sequence Intubation: administer medications and monitor hemodynamics during intubation. Anticipate hypotension due to positive pressure ventilation, PEEP, and sedation, and have vasopressors at the bedside to use if necessary [171] Secure endotracheal tube (ETT) using tape or commercial tube holder. Note the depth of insertion of ETT at teeth or lip [170] Perform key functions in the checklist for transportation of the critically ill Ventilation

Auscultate bilateral breath sounds Establish an appropriate oxygenation goal with the provider, send arterial blood gas, alert respiratory therapist and providers to values outside the desired range Establish an appropriate end-tidal CO2 goal with the provider, alert respiratory therapist and providers to values outside the desired range Suction ETT as needed, hyperoxygenate prior to suctioning [172]. Suctioning should be limited to two to three passes as this can increase intracranial pressure [173] Sedation

Establish an appropriate depth of sedation with the provider. Ensure sedation is in place while paralyzed For patients receiving neuromuscular-blocking agents, perform peripheral nerve stimulator (“train-of-four”) testing. As the neuromuscular-blocking agent efect dissipates, begin to wean sedation if appropriate, as a neurological examination should be prioritized Titrate sedation to desired goal, document depth of sedation using the Richmond Agitation–Sedation Scale (RASS) or the Riker Sedation–Agitation Scale (SAS) [124] If respiratory efort is dyssynchronous with the ventilator, alert respiratory therapist and provider to change ventilator settings as required. If this does not control dyssynchrony, increased sedation may be necessary [174] Recognize common complications of sedative medications such as hypotension and bradycardia; notify provider, and treat immediately using fuid bolus and/or vasopressor agents

PEEP positive end-expiratory pressure lethal condition with marked metabolic acidosis). For a child who requires frequent neurological examina- Clinical pearls tions, a remifentanil infusion may be useful, at a starting • Use the LEMON mnemonic to identify a difcult airway infusion rate of 0.1 μg/kg/min [163]. Remifentanil is a • Use the MOANS mnemonic to predict difculty with bag mask ventila- short-acting synthetic opioid that is metabolized via the tion plasma esterase system, resulting in a very short half-life • Identify patients who might beneft from an awake fberoptic intuba- (3–4 min). A recent study of children with severe TBI tion—unstable cervical spine, anticipated difcult intubation with relative stability in vital signs noted that once remifentanil was paused, the examiner • Always pre-oxygenate prior to intubation and use apneic oxygenation was able to perform a neurological examination within • Consider pre-treatment with fentanyl, lidocaine, and osmotherapy prior a median time of 9 min [163]. If continuous sedation is to intubation of the patient with elevated intracranial pressure needed after placement of an ICP monitor, options for • Avoid hypotension in most patients with acute brain injury. Consider appropriate sedation include: (1) an opioid infusion (fen- the use of etomidate or ketamine in these patients tanyl 1–4 μg/kg/h) with intermittent dosing of benzodi- • Patients with neurological illness frequently have contraindications to azepines or (2) an opioid infusion (fentanyl 1–4 μg/kg/h) succinylcholine. Consider the routine use of rocuronium in this population with a benzodiazepine infusion (midazolam 0.05–0.3 mg/ • Always plan in advance for two diferent failed airway scenarios— kg/h). A dexmedetomidine infusion at 0.2–1.2 mg/kg/h is “cannot intubate can ventilate,” and “cannot intubate cannot ventilate” also an option and is frequently combined with an opioid • Use pre- and post-intubation checklists for the intubated patient. Te use of dexmedetomidine is • Identify appropriate PaO2 and PaCO2 goals not well established in children with acute head injury. • Induced hyperventilation is generally reserved for patients with acute Finally, while information is currently limited, concern cerebral herniation or acute life-threatening intracranial pressure eleva- exists regarding the potential neurotoxicity of sedatives tion on the developing brain [164]. Te strongest evidence for • Use analgosedation as a frst-line measure in the intubated patient this comes from animal models, with limited evidence in • When a sedative infusion is necessary, propofol or dexmedetomidine clinical studies [165–169]. may be preferable to a benzodiazepine • Titrate to light sedation

Communication When communicating patient information to an accept- Author details ing or referring physician, consider including the key ele- 1 Neurocritical Care, OhioHealth - Riverside Methodist Hospital, Columbus, OH, ments listed in Table 6. USA. 2 Department of Pediatrics, Division of Critical Care Medicine, Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA. 3 Massa- chusetts General Hospital, Boston, MA, USA. 4 Departments of Neurosurgery Transport Considerations and Neurology, University of Michigan, Ann Arbor, MI, USA.

Consider the use of checklists prior to transport of Acknowledgements the critically ill. Te pre-transport checklist in Table 7 The authors are grateful for the contributions and insight provided by the fol- includes considerations specifc to airway, ventilation, lowing reviewers: Aaron Raleigh, BA, EMT-P; Jefrey Fong, PharmD, BCPS; and Victoria McCredie, MBChB, PhD, FRCPC, MRCPUK, UNCS. and sedation. Publisher’s Note Nursing Considerations Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional afliations. In the initial stages of a neurological emergency, the patient’s status may change rapidly. Frequent assessment of the patient’s neurological status should include assessment of the patient’s airway and respiratory status. Alert the care team immediately about changes in the patient’s ability to oxygenate, ventilate, and protect airway, and References anticipate the need for an advanced airway. * Important papers Topics that may be of particular signifcance to nursing ** Landmark papers are listed in Table 8. 1. Davis DP, Dunford JV, Ochs M, Park K, Hoyt DB. The use of quantitative end-tidal capnometry to avoid inadvertent severe hyperventilation in patients with head injury after paramedic rapid sequence intubation. J Trauma. 2004;56(4):808–14. 2. Coplin WM, Pierson DJ, Cooley KD, Newell DW, Rubenfeld GD. Implica- 23. Simpson GD, Ross MJ, McKeown DW, Ray DC. Tracheal intubation in the tions of extubation delay in brain-injured patients meeting standard critically ill: a multi-centre national study of practice and complications. weaning criteria. Am J Respir Crit Care Med. 2000;161(5):1530–6. Br J Anaesth. 2012;108(5):792–9. 3. McCredie VA, Ferguson ND, Pinto RL, et al. airway management 24. Henzler D, Cooper DJ, Tremayne AB, Rossaint R, Higgins A. Early strategies for brain-injured patients meeting standard criteria to modifable factors associated with fatal outcome in patients with consider extubation. A prospective cohort study. Ann Am Thorac Soc. severe traumatic brain injury: a case control study. Crit Care Med. 2017;14(1):85–93. 2007;35(4):1027–31. 4. Mackway-Jones K, Moulton C. Towards evidence based emergency 25. Stocchetti N, Furlan A, Volta F. Hypoxemia and arterial hypotension at medicine: best BETs from the Manchester Royal Infrmary. Gag refex the accident scene in head injury. J Trauma. 1996;40(5):764–7. and intubation. J Accid Emerg Med. 1999;16(6):444–5. 26. Trzeciak S, Jones AE, Kilgannon JH, et al. Signifcance of arterial 5. Gaither JB, Spaite DW, Bobrow BJ, et al. Balancing the potential risks hypotension after resuscitation from cardiac arrest. Crit Care Med. and benefts of out-of-hospital intubation in traumatic brain injury: the 2009;37(11):2895–903 (quiz 904). intubation/hyperventilation efect. Ann Emerg Med. 2012;60(6):732–6. 27. Schmidt UH, Kumwilaisak K, Bittner E, George E, Hess D. Efects of 6. Davis DP, Peay J, Sise MJ, et al. The impact of prehospital endotracheal supervision by attending anesthesiologists on complications of emer- intubation on outcome in moderate to severe traumatic brain injury. J gency tracheal intubation. Anesthesiology. 2008;109(6):973–7. Trauma. 2005;58(5):933–9. 28. Sawin PD, Todd MM, Traynelis VC, et al. Cervical spine motion with 7. Davis DP, Peay J, Serrano JA, et al. The impact of aeromedical response direct laryngoscopy and orotracheal intubation An in vivo cinefuoro- to patients with moderate to severe traumatic brain injury. Ann Emerg scopic study of subjects without cervical abnormality. Anesthesiology. Med. 2005;46(2):115–22. 1996;85(1):26–36. 8. Bernard SA, Nguyen V, Cameron P, et al. Prehospital rapid sequence 29. Collins SR, Blank RS. Fiberoptic intubation: an overview and update. intubation improves functional outcome for patients with severe Respir Care. 2014;59(6):865–78 (discussion 78–80). traumatic brain injury: a randomized controlled trial. Ann Surg. 30. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain 2010;252(6):959–65. injury in determining outcome from severe head injury. J Trauma. 9. **Apfelbaum JL, Hagberg CA, Caplan RA, et al. Practice guidelines for 1993;34(2):216–22. management of the difcult airway: an updated report by the Ameri- 31. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves can Society of Anesthesiologists Task Force on Management of the preoxygenation before intubation of hypoxic patients. Am J Respir Crit Difcult Airway. Anesthesiology. 2013;118(2):251–70. This is the standard Care Med. 2006;174(2):171–7. for the management of the difcult airway, particularly in the setting of the 32. Pavlov I, Medrano S, Weingart S. Apneic oxygenation reduces the inci- operating room. dence of hypoxemia during emergency intubation: a systematic review 10. Orebaugh SL. Difcult airway management in the emergency depart- and meta-analysis. Am J Emerg Med. 2017;35(8):1184–9. ment. J Emerg Med. 2002;22(1):31–48. 33. Binks MJ, Holyoak RS, Melhuish TM, et al. Apnoeic oxygenation during 11. Cook TM, Woodall N, Frerk C, Fourth National Audit P. Major intubation in the intensive care unit: a systematic review and meta- complications of airway management in the UK: results of the analysis. Heart Lung. 2017;46(6):452–7. Fourth National Audit Project of the Royal College of Anaesthetists 34. Oliveira JESL, Cabrera D, Barrionuevo P, et al. Efectiveness of apneic and the Difcult Airway Society. Part 1: anaesthesia. Br J Anaesth. oxygenation during intubation: a systematic review and meta-analysis. 2011;106(5):617–31. Ann Emerg Med. 2017;70(4):483–494e11. 12. Cook TM, Woodall N, Harper J, Benger J, Fourth National Audit P. Major 35. Tan E, Loubani O, Kureshi N, Green RS. Does apneic oxygenation complications of airway management in the UK: results of the Fourth prevent desaturation during emergency airway management? A National Audit Project of the Royal College of Anaesthetists and the systematic review and meta-analysis. Can J Anaesth. 2018;65(8):936–49. Difcult Airway Society. Part 2: intensive care and emergency depart- 36. Li J, Murphy-Lavoie H, Bugas C, Martinez J, Preston C. Complications of ments. Br J Anaesth. 2011;106(5):632–42. emergency intubation with and without paralysis. Am J Emerg Med. 13. Walls RM, Murphy M. Manual of emergency airway management. 3rd 1999;17(2):141–3. ed. Philadelphia: Lippincott Williams & Wilkins; 2008. 37. Walls RM. Rapid-sequence intubation in head trauma. Ann Emerg Med. 14. Mallampati SR, Gatt SP, Gugino LD, et al. A clinical sign to predict 1993;22(6):1008–13. difcult tracheal intubation: a prospective study. Can Anaesth Soc J. 38. Bedford RF, Persing JA, Pobereskin L, Butler A. Lidocaine or thio- 1985;32(4):429–34. pental for rapid control of intracranial hypertension? Anesth Analg. 15. Allen B, Ganti L, Desai B Intubation, airway, and mechanical ventilation. 1980;59(6):435–7. In: Quick hits in emergency medicine. New York: Springer; 2013. 39. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the manage- 16. Frerk C, Mitchell VS, McNarry AF, et al. Difcult Airway Society 2015 ment of severe traumatic brain injury, Fourth Edition. Neurosurgery. guidelines for management of unanticipated difcult intubation in 2017;80(1):6–15. adults. Br J Anaesth. 2015;115(6):827–48. 40. Donegan MF, Bedford RF. Intravenously administered lidocaine prevents 17. Sample G, Mccabe P, Vandruf T. Code critical airway teams improves intracranial hypertension during endotracheal suctioning. Anesthesiol- patient safety. Crit Care. 2010;14(Suppl 1):231. ogy. 1980;52(6):516–8. 18. Cooper RM, O’Sullivan E, Popat M, Behringer E, Hagberg CA. Difcult 41. Salhi B, Stettner E. In defense of the use of lidocaine in rapid sequence Airway Society guidelines for the management of tracheal extubation. intubation. Ann Emerg Med. 2007;49(1):84–6. Anaesthesia. 2013;68(2):217. 42. Reynolds SF, Hefner J. Airway management of the critically ill patient: 19. Law JA, Broemling N, Cooper RM, et al. The difcult airway with recom- rapid-sequence intubation. Chest. 2005;127(4):1397–412. mendations for management—part 1—difcult tracheal intubation 43. Seder DB, Mayer SA. Critical care management of subarachnoid hemor- encountered in an unconscious/induced patient. Can J Anaesth. rhage and ischemic stroke. Clin Chest Med. 2009;30(1):103–22. 2013;60(11):1089–118. 44. Kilgannon JH, Roberts BW, Reihl LR, et al. Early arterial hypotension 20. Myatra SN, Ahmed SM, Kundra P, et al. The All India Difcult Airway is common in the post-cardiac arrest syndrome and associated with Association 2016 guidelines for tracheal intubation in the Intensive increased in-hospital mortality. Resuscitation. 2008;79(3):410–6. Care Unit. Indian J Anaesth. 2016;60(12):922–30. 45. Oddo M, Bosel J. Participants in the International Multidisciplinary 21. **Higgs A, McGrath BA, Goddard C, et al. Guidelines for the man- Consensus Conference on Multimodality, M. Monitoring of brain and agement of tracheal intubation in critically ill adults. Br J Anaesth. systemic oxygenation in neurocritical care patients. Neurocrit Care. 2018;120(2):323–52. Widely accepted guidelines for the management of 2014;21(Suppl 2):S103–20. the difcult airway, specifc to the critically ill. 46. Prough DS, Lang J. Therapy of patients with head injuries: key param- 22. Jaber S, Amraoui J, Lefrant JY, et al. Clinical practice and risk factors for eters for management. J Trauma. 1997;42(5 Suppl):S10–8. immediate complications of endotracheal intubation in the inten- 47. Brinjikji W, Murad MH, Rabinstein AA, et al. Conscious sedation versus sive care unit: a prospective, multiple-center study. Crit Care Med. general anesthesia during endovascular acute ischemic stroke 2006;34(9):2355–61. treatment: a systematic review and meta-analysis. AJNR Am J Neurora- 69. Langsjo JW, Maksimow A, Salmi E, et al. S-ketamine anesthesia increases diol. 2015;36(3):525–9. cerebral blood fow in excess of the metabolic needs in humans. Anes- 48. Abou-Chebl A, Lin R, Hussain MS, et al. Conscious sedation versus thesiology. 2005;103(2):258–68. general anesthesia during endovascular therapy for acute anterior 70. Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Efectiveness of keta- circulation stroke: preliminary results from a retrospective, multicenter mine in decreasing intracranial pressure in children with intracranial study. Stroke. 2010;41(6):1175–9. hypertension. J Neurosurg Pediatr. 2009;4(1):40–6. 49. Dhakal LP, Diaz-Gomez JL, Freeman WD. Role of anesthesia for endo- 71. Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients vascular treatment of ischemic stroke: do we need neurophysiological with neurological injury? Anesth Analg. 2005;101(2):524–34. monitoring? Stroke. 2015;46(6):1748–54. 72. Hug CC Jr, McLeskey CH, Nahrwold ML, et al. Hemodynamic efects 50. Lowhagen Henden P, Rentzos A, Karlsson JE, et al. General anesthe- of propofol: data from over 25,000 patients. Anesth Analg. 1993;77(4 sia versus conscious sedation for endovascular treatment of acute Suppl):S21–9. ischemic stroke: the anstroke trial (anesthesia during stroke). Stroke. 73. Kovarik WD, Mayberg TS, Lam AM, Mathisen TL, Winn HR. Succinylcho- 2017;48(6):1601–7. line does not change intracranial pressure, cerebral blood fow velocity, 51. Schonenberger S, Uhlmann L, Hacke W, et al. Efect of conscious seda- or the electroencephalogram in patients with neurologic injury. Anesth tion vs general anesthesia on early neurological improvement among Analg. 1994;78(3):469–73. patients with ischemic stroke undergoing endovascular thrombec- 74. Martyn JA, Richtsfeld M. Succinylcholine-induced hyperkalemia in tomy: a randomized clinical trial. JAMA. 2016;316(19):1986–96. acquired pathologic states: etiologic factors and molecular mecha- 52. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the nisms. Anesthesiology. 2006;104(1):158–69. management of aneurysmal subarachnoid hemorrhage: a guideline for 75. Patanwala AE, Erstad BL, Roe DJ, Sakles JC. Succinylcholine is associated healthcare professionals from the American Heart Association/Ameri- with increased mortality when used for rapid sequence intubation of can Stroke Association. Stroke. 2012;43(6):1711–37. severely brain injured patients in the emergency department. Pharma- 53. Rodriguez-Luna D, Pineiro S, Rubiera M, et al. Impact of blood pressure cotherapy. 2016;36(1):57–63. changes and course on hematoma growth in acute intracerebral hem- 76. Lee C, Jahr JS, Candiotti KA, et al. Reversal of profound neuromuscular orrhage. Eur J Neurol. 2013;20(9):1277–83. block by sugammadex administered three minutes after rocuronium: a 54. Seneviratne J, Mandrekar J, Wijdicks EF, Rabinstein AA. Noninvasive comparison with spontaneous recovery from succinylcholine. Anesthe- ventilation in myasthenic crisis. Arch Neurol. 2008;65(1):54–8. siology. 2009;110(5):1020–5. 55. Abel M, Eisenkraft JB. Anesthetic implications of myasthenia gravis. Mt 77. Sorensen MK, Bretlau C, Gatke MR, Sorensen AM, Rasmussen LS. Rapid Sinai J Med. 2002;69(1–2):31–7. sequence induction and intubation with rocuronium-sugammadex 56. Austin N, Krishnamoorthy V, Dagal A. Airway management in cervical compared with succinylcholine: a randomized trial. Br J Anaesth. spine injury. Int J Crit Illn Inj Sci. 2014;4(1):50–6. 2012;108(4):682–9. 57. Hauswald M, Sklar DP, Tandberg D, Garcia JF. Cervical spine movement 78. Casey JD, Janz DR, Russell DW, et al. Bag-mask ventilation during tra- during airway management: cinefuoroscopic appraisal in human cheal intubation of critically ill adults. N Engl J Med. 2019;380(9):811–21. cadavers. Am J Emerg Med. 1991;9(6):535–8. 79. Lewis SR, Butler AR, Parker J, Cook TM, Smith AF. Videolaryngoscopy ver- 58. Rosenblatt WH, Wagner PJ, Ovassapian A, Kain ZN. Practice patterns in sus direct laryngoscopy for adult patients requiring tracheal intubation. managing the difcult airway by anesthesiologists in the United States. Cochrane Database Syst Rev. 2016;11:CD011136. Anesth Analg. 1998;87(1):153–7. 80. Griesdale DE, Chau A, Isac G, et al. Video-laryngoscopy versus direct 59. Malcharek MJ, Rogos B, Watzlawek S, et al. Awake fberoptic intubation laryngoscopy in critically ill patients: a pilot randomized trial. Can J and self-positioning in patients at risk of secondary cervical injury: a Anaesth. 2012;59(11):1032–9. pilot study. J Neurosurg Anesthesiol. 2012;24(3):217–21. 81. Lascarrou JB, Boisrame-Helms J, Bailly A, et al. video laryngos- 60. Ellis DY, Harris T, Zideman D. Cricoid pressure in emergency department copy vs direct laryngoscopy on successful frst-pass orotracheal rapid sequence tracheal intubations: a risk-beneft analysis. Ann Emerg intubation among ICU patients: a randomized clinical trial. JAMA. Med. 2007;50(6):653–65. 2017;317(5):483–93. 61. Nolan JP, Wilson ME. Orotracheal intubation in patients with potential 82. Sakles JC, Kalin L. The efect of stylet choice on the success rate of cervical spine injuries. An indication for the gum elastic bougie. Anaes- intubation using the GlideScope video laryngoscope in the emer- thesia. 1993;48(7):630–3. gency department. Acad Emerg Med. 2012;19(2):235–8. 62. Kill C, Risse J, Wallot P, et al. Videolaryngoscopy with glidescope reduces 83. Cormack RS, Lehane J. Difcult tracheal intubation in obstetrics. cervical spine movement in patients with unsecured cervical spine. J Anaesthesia. 1984;39(11):1105–11. Emerg Med. 2013;44(4):750–6. 84. Chakravarthy B, Seipp W. Direct laryngoscopy. In: Ganti L, editor. Atlas 63. Griesdale DE, Liu D, McKinney J, Choi PT. Glidescope(R) video-laryn- of emergency medicine procedures. New York: Springer; 2016. goscopy versus direct laryngoscopy for endotracheal intubation: a 85. Murray MJ, Vermeulen MJ, Morrison LJ, Waite T. Evaluation of systematic review and meta-analysis. Can J Anaesth. 2012;59(1):41–52. prehospital insertion of the laryngeal mask airway by primary 64. Su YC, Chen CC, Lee YK, Lee JY, Lin KJ. Comparison of video laryngo- care paramedics with only classroom mannequin training. CJEM. scopes with direct laryngoscopy for tracheal intubation: a meta-analysis 2002;4(5):338–43. of randomised trials. Eur J Anaesthesiol. 2011;28(11):788–95. 86. Bosch J, de Nooij J, de Visser M, et al. Prehospital use in emergency 65. De Jong A, Molinari N, Conseil M, et al. Video laryngoscopy versus patients of a laryngeal mask airway by ambulance paramedics is a direct laryngoscopy for orotracheal intubation in the intensive care safe and efective alternative for endotracheal intubation. Emerg unit: a systematic review and meta-analysis. Intensive Care Med. Med J. 2014;31(9):750–3. 2014;40(5):629–39. 87. Cook TM, Kelly FE. Time to abandon the ‘vintage’ laryngeal mask 66. Jaber S, Jung B, Corne P, et al. An intervention to decrease com- airway and adopt second-generation supraglottic airway devices as plications related to endotracheal intubation in the intensive care frst choice. Br J Anaesth. 2015;115(4):497–9. unit: a prospective, multiple-center study. Intensive Care Med. 88. McConnell RA, Kerlin MP, Schweickert WD, et al. Using a post- 2010;36(2):248–55. intubation checklist and time out to expedite mechanical ventilation 67. Chesnut RM, Marshall SB, Piek J, et al. Early and late systemic hypoten- monitoring: observational study of a quality improvement interven- sion as a frequent and fundamental source of cerebral ischemia tion. Respir Care. 2016;61(7):902–12. following severe brain injury in the Traumatic Coma Data Bank. Acta 89. Ventilation with lower tidal volumes as compared with traditional Neurochir Suppl (Wien). 1993;59:121–5. tidal volumes for acute lung injury and the acute respiratory distress 68. Moss E, Powell D, Gibson RM, McDowall DG. Efect of etomidate on syndrome. The Acute Respiratory Distress Syndrome Network. N Engl intracranial pressure and cerebral perfusion pressure. Br J Anaesth. J Med 2000;342(18):1301–8. 1979;51(4):347–52. 90. Bellani G, Grassi A, Sosio S, Foti G. Plateau and driving pressure in the presence of spontaneous breathing. Intensive Care Med. 2019;45(1):97–8. 91. Boone MD, Jinadasa SP, Mueller A, et al. The efect of positive end- 113. Mechem CC. Pulse oximetry. In: Finlay G, editors. UpToDate. Waltham, expiratory pressure on intracranial pressure and cerebral hemody- MA: UpToDate Inc. https://www.uptodate.com/home. Accessed 2 Jan namics. Neurocrit Care. 2017;26(2):174–81. 2019. 92. Muench E, Bauhuf C, Roth H, et al. Efects of positive end-expiratory 114. Dyer BA, White WA Jr, Lee D, Elkins L, Slayton DJ. The relationship pressure on regional cerebral blood fow, intracranial pressure, and between arterial carbon dioxide tension and end-tidal carbon dioxide brain tissue oxygenation. Crit Care Med. 2005;33(10):2367–72. tension in intubated adults with traumatic brain injuries who required 93. Fletcher JJ, Wilson TJ, Rajajee V, Davidson SB, Walsh JC. Changes emergency craniotomies. Crit Care Nurs Q. 2013;36(3):310–5. in therapeutic intensity level following airway pressure release 115. Helm M, Schuster R, Hauke J, Lampl L. Tight control of prehospital ventilation in severe traumatic brain injury. J Intensive Care Med. ventilation by capnography in major trauma victims. Br J Anaesth. 2018;33(3):196–202. 2003;90(3):327–32. 94. Nemer SN, Caldeira JB, Santos RG, et al. Efects of positive end-expir- 116. Hardman JG, Aitkenhead AR. Estimating alveolar dead space from the atory pressure on brain tissue oxygen pressure of severe traumatic arterial to end-tidal CO(2) gradient: a modeling analysis. Anesth Analg. brain injury patients with acute respiratory distress syndrome: a pilot 2003;97(6):1846–51. study. J Crit Care. 2015;30(6):1263–6. 117. Brain Trauma F, American Association of Neurological S, Congress of 95. Dumont TM, Visioni AJ, Rughani AI, Tranmer BI, Crookes B. Inappropri- Neurological S, et al. Guidelines for the management of severe trau- ate prehospital ventilation in severe traumatic brain injury increases matic brain injury. VI. Indications for intracranial pressure monitoring. J in-hospital mortality. J Neurotrauma. 2010;27(7):1233–41. Neurotrauma. 2007;24(Suppl 1):S37–44. 96. Davis DP, Idris AH, Sise MJ, et al. Early ventilation and outcome in 118. Citerio G, Cormio M. Sedation in neurointensive care: advances in patients with moderate to severe traumatic brain injury. Crit Care understanding and practice. Curr Opin Crit Care. 2003;9(2):120–6. Med. 2006;34(4):1202–8. 119. Riker RR, Fugate JE. Participants in the International Multi-disciplinary 97. Davis DP, Stern J, Sise MJ, Hoyt DB. A follow-up analysis of fac- Consensus Conference on Multimodality, M. Clinical monitoring scales tors associated with head-injury mortality after paramedic rapid in acute brain injury: assessment of coma, pain, agitation, and delirium. sequence intubation. J Trauma. 2005;59(2):486–90. Neurocrit Care. 2014;21(Suppl 2):S27–37. 98. Rangel-Castilla L, Lara LR, Gopinath S, et al. Cerebral hemodynamic 120. Samaniego EA, Mlynash M, Caulfeld AF, Eyngorn I, Wijman CA. Sedation efects of acute hyperoxia and hyperventilation after severe trau- confounds outcome prediction in cardiac arrest survivors treated with matic brain injury. J Neurotrauma. 2010;27(10):1853–63. hypothermia. Neurocrit Care. 2011;15(1):113–9. 99. Koenig MA, Bryan M, Lewin JL 3rd, et al. Reversal of transtentorial 121. Brook AD, Ahrens TS, Schaif R, et al. Efect of a nursing-implemented herniation with hypertonic saline. Neurology. 2008;70(13):1023–9. sedation protocol on the duration of mechanical ventilation. Crit Care 100. Qureshi AI, Geocadin RG, Suarez JI, Ulatowski JA. Long-term outcome Med. 1999;27(12):2609–15. after medical reversal of transtentorial herniation in patients with 122. Treggiari MM, Romand JA, Yanez ND, et al. Randomized trial of light supratentorial mass lesions. Crit Care Med. 2000;28(5):1556–64. versus deep sedation on mental health after critical illness. Crit Care 101. Oertel M, Kelly DF, Lee JH, et al. Efcacy of hyperventilation, Med. 2009;37(9):2527–34. blood pressure elevation, and metabolic suppression therapy in 123. Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Seda- controlling intracranial pressure after head injury. J Neurosurg. tion Scale: validity and reliability in adult intensive care unit patients. 2002;97(5):1045–53. Am J Respir Crit Care Med. 2002;166(10):1338–44. 102. *Muizelaar JP, Marmarou A, Ward JD, et al. Adverse efects of prolonged 124. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over hyperventilation in patients with severe head injury: a randomized clini- time in ICU patients: reliability and validity of the Richmond Agitation- cal trial. J Neurosurg. 1991;75(5):731–9. Randomized clinical trial that dem- Sedation Scale (RASS). JAMA. 2003;289(22):2983–91. onstrated that the use of prolonged hyperventilation may worsen outcomes. 125. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Seda- 103. Stocchetti N, Maas AI, Chieregato A, van der Plas AA. Hyperventilation tion-Agitation Scale for adult critically ill patients. Crit Care Med. in head injury: a review. Chest. 2005;127(5):1812–27. 1999;27(7):1325–9. 104. Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head 126. Deogaonkar A, Gupta R, DeGeorgia M, et al. Bispectral Index monitoring injury: efect on ischemic burden and cerebral oxidative metabolism. correlates with sedation scales in brain-injured patients. Crit Care Med. Crit Care Med. 2007;35(2):568–78. 2004;32(12):2403–6. 105. Kilgannon JH, Jones AE, Shapiro NI, et al. Association between arterial 127. *Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for hyperoxia following resuscitation from cardiac arrest and in-hospital the prevention and management of pain, agitation/sedation, delirium, mortality. JAMA. 2010;303(21):2165–71. immobility, and sleep disruption in adult patients in the ICU. Crit Care 106. Balan IS, Fiskum G, Hazelton J, Cotto-Cumba C, Rosenthal RE. Oximetry- Med. 2018;46(9):e825–73. Current standard for the use of sedation and guided reoxygenation improves neurological outcome after experi- analgesia in the critically ill. mental cardiac arrest. Stroke. 2006;37(12):3008–13. 128. Spies C, Macguill M, Heymann A, et al. A prospective, randomized, 107. Brucken A, Kaab AB, Kottmann K, et al. Reducing the duration of 100% double-blind, multicenter study comparing remifentanil with oxygen ventilation in the early reperfusion period after cardiopul- fentanyl in mechanically ventilated patients. Intensive Care Med. monary resuscitation decreases striatal brain damage. Resuscitation. 2011;37(3):469–76. 2010;81(12):1698–703. 129. Devabhakthuni S, Armahizer MJ, Dasta JF, Kane-Gill SL. Analgosedation: 108. Kilgannon JH, Jones AE, Parrillo JE, et al. Relationship between a paradigm shift in intensive care unit sedation practice. Ann Pharma- supranormal oxygen tension and outcome after resuscitation from cother. 2012;46(4):530–40. cardiac arrest. Circulation. 2011;123(23):2717–22. 130. Karabinis A, Mandragos K, Stergiopoulos S, et al. Safety and ef- 109. Bellomo R, Bailey M, Eastwood GM, et al. Arterial hyperoxia and cacy of analgesia-based sedation with remifentanil versus standard in-hospital mortality after resuscitation from cardiac arrest. Crit Care. hypnotic-based regimens in intensive care unit patients with brain 2011;15(2):R90. injuries: a randomised, controlled trial [ISRCTN50308308]. Crit Care. 110. Wang CH, Chang WT, Huang CH, et al. The efect of hyperoxia on 2004;8(4):R268–80. survival following adult cardiac arrest: a systematic review and meta- 131. Iyer VN, Hoel R, Rabinstein AA. Propofol infusion syndrome in patients analysis of observational studies. Resuscitation. 2014;85(9):1142–8. with refractory status epilepticus: an 11-year clinical experience. Crit 111. Elmer J, Scutella M, Pullalarevu R, et al. The association between Care Med. 2009;37(12):3024–30. hyperoxia and patient outcomes after cardiac arrest: analysis of a high- 132. Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs mida- resolution database. Intensive Care Med. 2015;41(1):49–57. zolam or propofol for sedation during prolonged mechanical ventila- 112. Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest tion: two randomized controlled trials. JAMA. 2012;307(11):1151–60. care: 2010 American Heart Association Guidelines for Cardiopulmo- 133. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the nary Resuscitation and Emergency Cardiovascular Care. Circulation. management of pain, agitation, and delirium in adult patients in the 2010;122(18 Suppl 3):S768–86. intensive care unit. Crit Care Med. 2013;41(1):263–306. 134. Grof TM, Bledsoe KA. Evaluating the use of dexmedetomidine in neuro- 156. Filanovsky Y, Miller P, Kao J. Myth: Ketamine should not be used as critical care patients. Neurocrit Care. 2010;12(3):356–61. an induction agent for intubation in patients with head injury. CJEM. 135. Brown RL, Brunn MA, Garcia VF. Cervical spine injuries in children: a 2010;12(2):154–7. review of 103 patients treated consecutively at a level 1 pediatric 157. Sehdev RS, Symmons DA, Kindl K. Ketamine for rapid sequence induc- trauma center. J Pediatr Surg. 2001;36(8):1107–14. tion in patients with head injury in the emergency department. Emerg 136. Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the manage- Med Australas. 2006;18(1):37–44. ment of pediatric severe traumatic brain injury, third edition: update 158. Skippen P, Seear M, Poskitt K, et al. Efect of hyperventilation on of the brain trauma foundation guidelines, executive summary. Pediatr regional cerebral blood fow in head-injured children. Crit Care Med. Crit Care Med. 2019;20(3):280–9. 1997;25(8):1402–9. 137. Wani TM, Bissonnette B, Engelhardt T, et al. The pediatric airway: histori- 159. Kochanek PM, Carney N, Adelson PD, et al. Guidelines for the acute cal concepts, new fndings, and what matters. Int J Pediatr Otorhi- medical management of severe traumatic brain injury in infants, nolaryngol. 2019;121:29–33. children, and adolescents–second edition. Pediatr Crit Care Med. 138. Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: pediatric 2012;13(Suppl 1):S1–82. advanced life support: 2010 American Heart Association Guidelines for 160. Downard C, Hulka F, Mullins RJ, et al. Relationship of cerebral perfusion Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. pressure and survival in pediatric brain-injured patients. J Trauma. Circulation. 2010;122(18 Suppl 3):S876–908. 2000;49(4):654–8 (discussion 8–9). 139. Duf JP, Topjian A, Berg MD, et al. 2018 American Heart Association 161. Elias-Jones AC, Punt JA, Turnbull AE, Jaspan T. Management and focused update on pediatric advanced life support: an update to outcome of severe head injuries in the Trent region 1985-90. Arch Dis the American Heart Association guidelines for cardiopulmonary Child. 1992;67(12):1430–5. resuscitation and emergency cardiovascular care. Circulation. 162. Freeman SS, Udomphorn Y, Armstead WM, Fisk DM, Vavilala MS. 2018;138(23):e731–9. Young age as a risk factor for impaired cerebral autoregulation after 140. Khine HH, Corddry DH, Kettrick RG, et al. Comparison of cufed and moderate to severe pediatric traumatic brain injury. Anesthesiology. uncufed endotracheal tubes in young children during general anes- 2008;108(4):588–95. thesia. Anesthesiology. 1997;86(3):627–31 (discussion 27A). 163. Hungerford JL, O’Brien N, Moore-Clingenpeel M, et al. Remifentanil for 141. King BR, Baker MD, Braitman LE, Seidl-Friedman J, Schreiner MS. sedation of children with traumatic brain injury. J Intensive Care Med. Endotracheal tube selection in children: a comparison of four methods. 2019;34(7):557–62. Ann Emerg Med. 1993;22(3):530–4. 164. Nemergut ME, Aganga D, Flick RP. Anesthetic neurotoxicity: what to tell 142. Wheeler M, Coté C, Todres ID. The pediatric airway. In: Lerman J, Coté the parents? Paediatr Anaesth. 2014;24(1):120–6. C, Todres ID, editors. A practice of anesthesia for infants and children. 165. Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic Philadelphia: Saunders-Elsevier; 2009. p. 237. neurodegeneration in the developing brain. Proc Natl Acad Sci USA. 143. Weiss M, Dullenkopf A, Fischer JE, et al. Prospective randomized con- 2002;99(23):15089–94. trolled multi-centre trial of cufed or uncufed endotracheal tubes in 166. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to small children. Br J Anaesth. 2009;103(6):867–73. common anesthetic agents causes widespread neurodegeneration 144. Phipps LM, Thomas NJ, Gilmore RK, et al. Prospective assessment of in the developing rat brain and persistent learning defcits. J Neurosci. guidelines for determining appropriate depth of endotracheal tube 2003;23(3):876–82. placement in children. Pediatr Crit Care Med. 2005;6(5):519–22. 167. Loepke AW, Soriano SG. An assessment of the efects of general 145. Patel R, Lenczyk M, Hannallah RS, McGill WA. Age and the onset of anesthetics on developing brain structure and neurocognitive function. desaturation in apnoeic children. Can J Anaesth. 1994;41(9):771–4. Anesth Analg. 2008;106(6):1681–707. 146. Weiss M, Gerber AC. Rapid sequence induction in children—it’s not a 168. Paule MG, Li M, Allen RR, et al. Ketamine anesthesia during the frst matter of time! Paediatr Anaesth. 2008;18(2):97–9. week of life can cause long-lasting cognitive defcits in rhesus monkeys. 147. Lawes EG, Campbell I, Mercer D. Infation pressure, gastric insufation Neurotoxicol Teratol. 2011;33(2):220–30. and rapid sequence induction. Br J Anaesth. 1987;59(3):315–8. 169. Pohl D, Bittigau P, Ishimaru MJ, et al. N-Methyl-D-aspartate antagonists 148. Moynihan RJ, Brock-Utne JG, Archer JH, Feld LH, Kreitzman TR. The and apoptotic cell death triggered by head trauma in developing rat efect of cricoid pressure on preventing gastric insufation in infants brain. Proc Natl Acad Sci USA. 1999;96(5):2508–13. and children. Anesthesiology. 1993;78(4):652–6. 170. Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, 149. Weiler N, Heinrichs W, Dick W. Assessment of pulmonary mechanics et al. (2015) Adult advanced cardiovascular life support. Circulation. and gastric infation pressure during mask ventilation. Prehospital 2015;132(Supp 2):S444–64. Disaster Med. 1995;10(2):101–5. 171. Franklin C, Samuel J, Hu TC. Life-threatening hypotension associated 150. Brock-Utne JG. Is cricoid pressure necessary? Paediatr Anaesth. with emergency intubation and the initiation of mechanical ventilation. 2002;12(1):1–4. Amer J Emer Med. 1994;12(4):425–28. 151. Landsman I. Cricoid pressure: indications and complications. Paediatr 172. Overend TJ, Anderson CM, Brooks D, Cicutto L, Keim M, McAuslan Anaesth. 2004;14(1):43–7. D, Nononyama M. Updating the evidence base for suctioning adult 152. Lev R, Rosen P. Prophylactic lidocaine use preintubation: a review. J patients: a systematic review. Can Respir J 2009;16(3):e6–17. Emerg Med. 1994;12(4):499–506. 173. Gholamzadeh S, Javadi M. Efect of endotracheal suctioning on intrac- 153. Sagarin MJ, Chiang V, Sakles JC, et al. Rapid sequence intubation ranial pressure in severe head-injured patients. Crit Care. 2009;13(Suppl for pediatric emergency airway management. Pediatr Emerg Care. 1): 80. https://doi.org/10.1186/cc7244. 2002;18(6):417–23. 174. Mellott KG, Grap MJ, Munro, CL, Sessler CN, Wetzel PA. Patient ventilator 154. Gronert GA. Cardiac arrest after succinylcholine: mortality greater dyssynchrony: clinical signifcance and implications for practice. Crit with rhabdomyolysis than receptor upregulation. Anesthesiology. Care Nurse 2009;29(6):41–55. 2001;94(3):523–9. 155. Larach MG, Rosenberg H, Gronert GA, Allen GC. Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies. Clin Pediatr (Phila). 1997;36(1):9–16.