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">Fast Facts</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. As such, we favor the <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">analgosedation approach</a>, which addresses patients’ pain first and sedation requirements second. In this section, we cover the key principles of:</p><ul class="onepub-jats-list-unordered"><li><p><a href="#1" class="onepub-link-primary">Analgesia, Sedation, and Analgosedation</a></p></li><li><p><a href="#2" class="onepub-link-primary">ICU Delirium</a></p></li></ul><div class="onepub-jats-section-title"><h2 id="1" class="onepub-jats-title onepub-page-anchor">Analgesia, Sedation, and Analgosedation</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?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" 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?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" class="onepub-link-primary" target="_blank">readiness for extubation</a>. (See the section on <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?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" 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?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" 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.</p></li></ul><div class="onepub-jats-section-title"><h3 class="onepub-jats-title">Medications</h3></div><p>No conclusive trials have demonstrated a benefit of one sedative medication over another.</p><p><b>Common regimens</b> 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 typical dose and associated adverse effects.</p><div class="onepub-jats-fig panel figure"><div class="onepub-jats-caption"><h3 class="onepub-jats-title">Sedatives and Analgesics in Common Use in the ICU</h3></div><img src="content_item_media_uploads/pabwze34bauqcvrqq1jm.jpg" alt="content_item_media_uploads/pabwze34bauqcvrqq1jm.jpg"><p class="onepub-jats-attrib">(Source: <a href="https://www.nejm.org/doi/full/10.1056/NEJMra1208705" class="onepub-link-primary" target="_blank">Sedation and Delirium in the Intensive Care Unit.</a> N Engl J Med 2014.)</p></div><p><b>Titration:</b> 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 patient undergoing mechanical ventilation are 3 to 4 for the SAS and -2 to 0 for the RASS.</p><div class="onepub-jats-fig panel figure"><div class="onepub-jats-caption"><h3 class="onepub-jats-title">Sedation Scales for Patients in the ICU</h3></div><img src="content_item_media_uploads/nejmra1208705_t2.jpg" alt="content_item_media_uploads/nejmra1208705_t2.jpg"><p class="onepub-jats-attrib">(Source: <a href="https://www.nejm.org/doi/full/10.1056/NEJMra1208705" class="onepub-link-primary" target="_blank">Sedation and Delirium in the Intensive Care Unit.</a> N Engl J Med, 2014.)</p></div><div class="onepub-jats-section-title"><h2 id="2" class="onepub-jats-title onepub-page-anchor">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</p></li></ul><p>Delirium is important to recognize because it is associated with increased risk of mortality and long-term cognitive dysfunction. In the <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. Delirium is even an <a href="https://jamanetwork.com/journals/jama/fullarticle/198503" class="onepub-link-primary" target="_blank">independent predictor</a> of mortality in patients who are undergoing mechanical ventilation.</p><p>Delirium is common in the ICU especially in older patients who have received sedatives (particularly benzodiazepines) and in patients with more-severe illness. A complex interplay of factors contributes to delirium, as demonstrated in the following figure:</p><div class="onepub-jats-fig panel figure"><div class="onepub-jats-caption"><h2 id="" class="onepub-jats-title onepub-page-anchor">Causes and Interactions of Pain, Agitation, and Delirium</h2><p>Drugs and other treatments for pain, agitation, and delirium form an “ICU triad” cognitive management analogous to the “triad of anesthesia,” which highlights interactions among hypnotics, analgesics, and muscle relaxants to encourage balanced anesthesia. The “ICU triad” concept highlights that changing one element is unlikely to be as effective as a coordinated approach.</p></div><img src="content_item_media_uploads/yo7a6ltpqnwxx4wyw7q3.jpg" alt="content_item_media_uploads/yo7a6ltpqnwxx4wyw7q3.jpg"><p class="onepub-jats-attrib">(Source: <a href="https://www.nejm.org/doi/full/10.1056/NEJMra1208705" class="onepub-link-primary" target="_blank">Sedation and Delirium in the Intensive Care Unit.</a> N Engl J Med 2014.)</p></div><div class="onepub-jats-section-title"><h3 class="onepub-jats-title">Diagnosis</h3></div><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 screening but do not distinguish between hypoactive and hyperactive subtypes of delirium.</p><div class="onepub-div-table-container"><div class="onepub-jats-table-wrap panel"><table frame="void"><tbody><tr><th>Scoring Systems for the Diagnosis of Delirium in Critically Ill Patients</th></tr><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>The patient must be sufficiently awake (RASS<b>†</b> score, −3 or more) for assessment according to the following criteria:<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• An acute change from mental status at baseline or fluctuating mental status during the past 24 hrs (must be true to be positive)<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• More than two errors on a 10-point test of attention to voice or pictures (must be true to be positive)<tt><br class="onepub-jats-br"></tt>If the RASS is not 0 and the above two criteria are positive, the patient is delirious.<tt><br class="onepub-jats-br"></tt>If the RASS is 0 and the above two criteria are positive, test for disorganized thinking using four yes/no questions and a two-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><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>The patient must show at least a response to mild or moderate stimulation. Then score one point for each of the following features, as assessed in the manner thought appropriate by the clinician:<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Anything other than “normal wakefulness”<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Inattention<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Disorientation<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Hallucination<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Psychomotor agitation<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Inappropriate speech or mood<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Disturbance in sleep or wake cycle<tt><br class="onepub-jats-br"></tt>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Fluctuation in symptoms</td></tr></tbody></table><div class="onepub-jats-table-wrap-foot"><p>* Data are from <a href="https://jamanetwork.com/journals/jama/fullarticle/194422?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" class="onepub-link-primary" target="_blank">Ely et al.</a><tt><br class="onepub-jats-br"></tt>† 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;utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" class="onepub-link-primary" target="_blank">Richmond Agitation–Sedation Scale.</a><tt><br class="onepub-jats-br"></tt>‡ Data are from <a href="https://link.springer.com/article/10.1007%2Fs001340100909?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" 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" class="onepub-link-primary" target="_blank">Sedation and Delirium in the ICU.</a> N Engl J Med 2014.)</p></div></div></div><div class="onepub-jats-section-title"><h3 class="onepub-jats-title">Prevention</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> 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?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" 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?utm_medium=referral&amp;utm_source=r360&amp;utm_campaign=criticalcare" 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, nonopioid analgesia, cognitive stimulation, vision and hearing aids, and adequate hydration can prevent delirium and may help a patient who can participate in these measures.</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.</p></li></ul></div></div></div>