A brief refresher with useful tables, figures, and research summaries

Fast Facts

<div class="onepub-jats-front" id="10.1056/r360.i000262-front"><div class="onepub-jats-metadata two-column table"><div class="onepub-jats-row"><div class="onepub-jats-cell"><div class="onepub-jats-metadata-group"></div></div></div></div><div class="onepub-jats-metadata centered"></div></div><div class="onepub-jats-body" id="10.1056/r360.i000262-body"><div class="onepub-jats-section-container"><div class="onepub-fast-facts"><div class="onepub-jats-main-title"><h6 class="onepub-jats-title fast-facts">Sedation &amp; Delirium</h6></div><p class="subtitle">A brief refresher with useful tables, figures, and research summaries</p><div class="onepub-jats-section-title"><h1 class="onepub-jats-title">Sedation and ICU Delirium</h1></div><p>Sedation and analgesia are important treatments for critically ill patients who often receive painful interventions in the intensive care unit (ICU) and for whom an ICU stay can be a traumatic experience. As sedation became more commonly used for comfort, we increasingly recognized that too much sedation causes adverse outcomes such as delirium, which is associated with increased morbidity and mortality. In this section, we cover the key principles of:</p><ul class="onepub-jats-list-unordered"><li><p><a href="https://resident360.nejm.org/rotation-prep/critical-care/sedation-and-delirium/fast-facts#1" class="onepub-link-primary" target="_blank">Sedation</a></p></li><li><p><a href="https://resident360.nejm.org/rotation-prep/critical-care/sedation-and-delirium/fast-facts#2" class="onepub-link-primary" target="_blank">ICU Delirium</a><tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt></p></li></ul><div class="onepub-jats-section-title"><h2 class="onepub-jats-title">Sedation</h2></div><p>There are many reasons for sedation in the ICU, such as to prevent dyssynchrony between a patient and the ventilator and to prevent the patient from removing his or her endotracheal tubes or intravenous catheters. However, increasing evidence indicates that minimizing the use of sedation is beneficial.</p><ul class="onepub-jats-list-unordered"><li><p>In a <a href="http://www.nejm.org/doi/10.1056/NEJM200005183422002" class="onepub-link-primary" target="_blank">randomized trial</a> published in 2000, daily interruption of sedative-drug infusions was associated with shorter duration of mechanical ventilation and length of stay in the ICU. This spontaneous awakening trial (SAT) has now been combined with the spontaneous breathing trial (SBT) to test <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60105-1/abstract" class="onepub-link-primary" target="_blank">readiness for extubation</a>. (See the section on&nbsp;<a href="https://resident360.nejm.org/rotation-prep/critical-care/ventilation/fast-facts" class="onepub-link-primary" target="_blank">Ventilation</a> for more information about weaning from the ventilator.)</p></li><li><p>In contrast, a 2012 <a href="http://jamanetwork.com/journals/jama/fullarticle/1380160" class="onepub-link-primary" target="_blank">study</a> found that when using a sedation protocol that emphasized minimizing the overall amount of sedation, a daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay.</p></li><li><p>Results of several subsequent <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60105-1/fulltext" class="onepub-link-primary" target="_blank">studies</a> have concluded that minimizing the dose and duration of sedation is associated with improved outcomes.</p></li><li><p>Some indications require deep sedation, such as intracranial hypertension, severe respiratory failure, refractory status epilepticus, and use of neuromuscular blockade.&nbsp;<tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt></p></li></ul><div class="onepub-jats-section-title"><h3 class="onepub-jats-title"><b>Medications</b></h3></div><p>No conclusive trials have demonstrated a benefit of one sedative medication over another. An&nbsp;<a href="https://www.nejm.org/doi/10.1056/NEJMoa1904710" class="onepub-link-primary" target="_blank">open-label trial</a> showed that dexmedetomidine was associated with significantly more adverse effects when used as a single agent for early sedation, as compared with the standard care (propofol, midazolam), while another <a href="https://www.nejm.org/doi/10.1056/NEJMoa2024922" class="onepub-link-primary" target="_blank">trial</a> showed no differences.</p><p>Common regimens for mechanically ventilated patients include propofol infusion or combination fentanyl and midazolam infusions (pairing analgesic and amnesic effects). The table below lists the common sedatives and analgesics used in the ICU along with their doses and adverse effects.</p><p><a href="content_item_media_uploads/pabwze34bauqcvrqq1jm.jpg" class="onepub-link-primary" target="_self"><b></b></a></p><div class="onepub-jats-fig panel"><h5 class="onepub-jats-label"><a href="content_item_media_uploads/pabwze34bauqcvrqq1jm.jpg" class="onepub-link-primary" target="_self"><b>Figure&nbsp;1</b></a></h5><a href="content_item_media_uploads/pabwze34bauqcvrqq1jm.jpg" class="onepub-link-primary" target="_self"><b><img src="content_item_media_uploads/pabwze34bauqcvrqq1jm.jpg" alt=""></b></a></div><b>(Source: <a href="http://www.nejm.org/doi/full/10.1056/NEJMra1208705#ref13" class="onepub-link-primary" target="_blank">Sedation and Delirium in the Intensive Care Unit.</a>&nbsp;N Engl J Med 2014.)</b><p></p><p>To balance the right amount of sedation, titrate dose to a target on a validated scale, such as the Riker Sedation–Agitation Scale (SAS) or the Richmond Agitation–Sedation Scale (RASS). Typical goals for a mechanically ventilated patient are 3 to 4 for the SAS and -2 to 0 for the RASS.</p><p><a href="content_item_media_uploads/sviwalkxzp15tvtklr33.gif" class="onepub-link-primary onepub-image-fullsize" target="_self"><img src="content_item_media_uploads/sviwalkxzp15tvtklr33.gif" alt=""></a><b>(Source: <a href="http://www.nejm.org/doi/full/10.1056/NEJMra1208705#ref13" class="onepub-link-primary" target="_blank">Sedation and Delirium in the Intensive Care Unit.</a> N Engl J Med, 2014.)</b></p><p class="hr"></p><div class="onepub-jats-section-title"><h2 class="onepub-jats-title">ICU Delirium</h2></div><p>Delirium is an acute-onset, fluctuating change in cognition, attention, and/or awareness that is not directly caused by an acute medical condition. It can be classified as:</p><ul class="onepub-jats-list-unordered"><li><p>hypoactive: inattention, disordered thinking, decreased consciousness</p></li><li><p>hyperactive: hallucinations, agitation</p></li><li><p>mixed: both hyperactive and hypoactive features<tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt></p></li></ul><p>It’s important to recognize delirium, which is associated with increased mortality and long-term cognitive dysfunction. In the&nbsp;<a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1301372?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" class="onepub-link-primary" target="_blank">BRAIN-ICU study</a>, patients who experienced longer duration of delirium in the ICU had more profound cognitive decline at 12 months after discharge.</p><p>Delirium is very common in the ICU, and it’s more likely to occur in older patients who have received sedatives (especially benzodiazepines) and in patients with more severe illness. A complex interplay of factors contributes to delirium (see figure below).</p><div class="onepub-jats-section-title"><h3 class="onepub-jats-title">Causes and Interactions of Pain, Agitation, and Delirium</h3></div><p><a href="content_item_media_uploads/yo7a6ltpqnwxx4wyw7q3.jpg" class="onepub-link-primary" target="_self"><b></b></a></p><div class="onepub-jats-fig panel"><h5 class="onepub-jats-label"><a href="content_item_media_uploads/yo7a6ltpqnwxx4wyw7q3.jpg" class="onepub-link-primary" target="_self"><b>Figure&nbsp;3</b></a></h5><a href="content_item_media_uploads/yo7a6ltpqnwxx4wyw7q3.jpg" class="onepub-link-primary" target="_self"><b><img src="content_item_media_uploads/yo7a6ltpqnwxx4wyw7q3.jpg" alt=""></b></a></div><b>(Source:&nbsp;<a href="http://www.nejm.org/doi/full/10.1056/NEJMra1208705?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare#ref13" class="onepub-link-primary" target="_blank">Sedation and Delirium in the Intensive Care Unit.</a>&nbsp;N Engl J Med 2014.)</b><p></p><p>Delirium is a clinical diagnosis that is made after ruling out other causes of altered mental status (e.g., hypercarbia, drug intoxication, hepatic encephalopathy, uremia, primary central nervous system pathology). Validated scoring systems (see examples in the table below) can aid diagnosis and help with screening for delirium, but they don’t distinguish between hypoactive and hyperactive subtypes.</p><div class="onepub-jats-section-title"><h3 class="onepub-jats-title">Scoring Systems for the Diagnosis of Delirium in Critically Ill Patients</h3></div><div class="onepub-div-table-container"><div class="onepub-jats-table-wrap panel"><table><tbody><tr><td><b>Confusion Assessment Method for the ICU (CAM-ICU)†</b><tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt> Scoring is positive or negative according to the presence or absence of criteria listed<tt><br class="onepub-jats-br"></tt> Patient must be sufficiently awake (RASS* score, −3 or more) for assessment according to the following criteria:<tt><br class="onepub-jats-br"></tt><ul class="onepub-jats-list-unordered"><li><p>An acute change from mental status at baseline or fluctuating mental status during the past 24 hr (must be true to be positive)</p></li><li><p>More than 2 errors on a 10-point test of attention to voice or pictures (must be true to be positive)</p></li><li><p>If the RASS is not 0 and the above two criteria are positive, the patient is delirious</p></li><li><p>If the RASS is 0 and the above two criteria are positive, test for disorganized thinking using 4 yes/no questions and a 2-step command; &gt;1 error means the patient is delirious; ≤1 error excludes delirium<tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt></p></li></ul><b>Intensive Care Delirium Screening Checklist (ICDSC)‡</b><tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt> A score of ≥4 is positive for delirium (with scores of 1 to 3 termed “subsyndromal delirium”)<tt><br class="onepub-jats-br"></tt> Patient must show at least a response to mild or moderate stimulation. Then score 1 point for each of the following features, as assessed in the manner thought appropriate by the clinician:<tt><br class="onepub-jats-br"></tt><ul class="onepub-jats-list-unordered"><li><p>Anything other than “normal wakefulness”</p></li><li><p>Inattention</p></li><li><p>Disorientation</p></li><li><p>Hallucination</p></li><li><p>Psychomotor agitation</p></li><li><p>Inappropriate speech or mood</p></li><li><p>Disturbance in sleep or wake cycle</p></li><li><p>Fluctuation in symptoms</p></li></ul></td></tr></tbody></table></div><div class="onepub-jats-subsection-title"><h6 class="onepub-jats-title">* RASS denotes <a href="https://www.atsjournals.org/doi/10.1164/rccm.2107138?url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org&amp;rfr_dat=cr_pub++0pubmed&amp;" class="onepub-link-primary" target="_blank">Richmond Agitation–Sedation Scale.</a>&nbsp;† Data are from <a href="https://jamanetwork.com/journals/jama/fullarticle/194422" class="onepub-link-primary" target="_blank">Ely et al.</a> ‡ Data are from <a href="https://link.springer.com/article/10.1007%2Fs001340100909" class="onepub-link-primary" target="_blank">Bergeron et al.</a><tt><br class="onepub-jats-br"></tt>(Adapted from: <a href="https://www.nejm.org/doi/full/10.1056/NEJMra1208705?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" class="onepub-link-primary" target="_blank">Sedation and Delirium in the ICU.</a> N Engl J Med 2014.)</h6></div></div><div class="onepub-jats-section-title"><h3 class="onepub-jats-title"><b>Prevention</b></h3></div><ul class="onepub-jats-list-unordered"><li><p><a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60658-9/abstract?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" class="onepub-link-primary" target="_blank">Early mobilization</a>&nbsp;has been shown to decrease the duration of delirium by 50% in medical ICU patients.</p></li><li><p>In surgical populations (but not medical ICU patients), low-dose haloperidol and risperidone have been shown to reduce duration of delirium, but a <a href="https://doi.org/10.1001/jama.2018.0160" class="onepub-link-primary" target="_blank">study</a> published in 2018 did not show a benefit for low-dose haloperidol<a href="https://doi.org/10.1001/jama.2018.0160" class="onepub-link-primary" target="_blank">.</a></p></li><li><p>Some studies suggest that using dexmedetomidine as a sedative is associated with lower rates of delirium than benzodiazepines.</p></li><li><p>Outside the ICU, frequent orientation, noise reduction, cognitive stimulation, vision and hearing aids, and adequate hydration can prevent delirium and may help a patient who can participate in these measures.<tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt></p></li></ul><div class="onepub-jats-section-title"><h3 class="onepub-jats-title">Treatment</h3></div><ul class="onepub-jats-list-unordered"><li><p>To date, no well-studied therapies have been shown to effectively treat delirium.</p></li><li><p>Antipsychotics (e.g., haloperidol and quetiapine) are commonly used for acute agitation, but they have not been shown to reduce duration of delirium<tt><br class="onepub-jats-br"></tt><tt><br class="onepub-jats-br"></tt></p></li></ul></div></div></div>