Question 21

College answer

Aim: To explore the evidence and practice surrounding the use of sedatives in the ICU.
Key sources include: ANZICS trials, major landmark trials, and current practice guidelines for sedation. CanMEDS Medical Expert, Scholar.
Discussion: The RASS score is a commonly used scale for agitation/sedation in the ICU daily practice and sedation research. Candidates are expected to understand the evidence base of clinical practice and the drugs we use routinely.
The successful candidate utilised their bedside experience, had a practical approach to the answer by addressing the subheadings and had a broad understanding of the literature on dexmedetomidine.
Part b required only brief outline of the key results and conclusions of the relevant trials. Candidates are not expected to go into depth about individual trials given the time constraints of the examination. A broad outline of the trial aim, results and conclusions sufficed.
The successful candidate demonstrated familiarity with the current research particularly in relation to the ANZICS SPICE trial. Candidates passed if they outlined the major findings and included brief notes on trial design.
The number per trial arm, journal name and date published, and secondary outcomes were NOT required. The trials listed below are provided to guide candidates with information to aid future study.
-Spice III
NEJM May 2019
In ventilated patients does Dexmedetomidine as the primary sedative agent compared with usual sedations affect 90-day mortality?
-MINDEX/PRODEX trials
JAMA 2012
Is Dexmedetomidine inferior to propofol or midazolam in achieving target sedation level?
-DahLIA trial
JAMA March 2016
Effect of Dexmedetomidine added to standard care on ventilator free time in patients with agitated delirium.
-Low dose nocturnal dexmedetomidine prevents ICU delirium: a RCT placebo-controlled trail
Skrobik AJRCM 2018
-DESIRE
Effect of Dexmedetomidine on Mortality and ventilator free days in patients requiring mechanical ventilation with sepsis RCT
JAMA 2017

Discussion

a) This breakdown of the RASS lists much more stuff than you could possibly be expected to write in four minutes, and represents a sort of disorganised pool of variably valid points, where readers can fish around for the ones they prefer.

Purpose of the RASS:

• Quantify the depth of sedation or the level of arousal/agitation as a value
• Offer a reproducible bedside method of measuring this value using precise criteria
• Simplify the selection and prescription of sedation targets
• Optimise the dosing of sedation by providing a measurable endpoint 
• Allow the comparison of sedation/agitation measurements for research

Components of the RASS:

• Level of spontaneous activity
• Eye response to voice
• Eye contact (and duration of eye contact)
• Response to physical stimuli

Advantages of the RASS

• RASS has good reliability and validity across a range of critically ill populations (Ely et al, 2003)
• The inter-rater reliability is very good (Almgren et al, 2010)
• It is easy to administer and is not culturally specific (which means it translates easily across cultural and language boundaries)
• Unlike many other scales the RASS has good "resolution" at the mild-moderate range of sedation (corresponding to RASS scores of +1 to -4), allowing the fine titration of sedation
• The scale has been studied extensively and compared to numerous other scales, making it a de facto "gold standard" in the field
• It is referenced in analgesia and sedation guidelines (such as the 2021 KSCCM guidelines and the 2018 SCCM guidelines)
• The familiarity with this scale means less time spent on orienting and training new staff (as compared to adopting a less widely known scale)

Disadvantages of the RASS

• It will not work on patients who are deaf (and will not hear the assessor's "loud speaking voice")
• It will not work on blind patients (as they will not make eye contact)
• Some people with autism spectrum disorders actively avoid eye contact
• It is difficult to assess in patients with severe sensory loss, eg. those with high spinal injury
• It can't be used to assess the level of sedation in patients who are paralysed or under the effect of neuromuscular junction blockers
• The scoring of the level of agitation (above +1) relies on the observation of specific behaviours, which can be transient and subjective, i.e. a patient is +1 until they are suddenly a +4 and throwing a chair at you. 
• Repeated observations will yield a progressively higher score

b)

In order of appearance, here are some of the trials the candidates could have listed. The SAQ wording suggests that originally the candidates were expected to remark on the methodology of the studies they listed, but the examiner comments ("a broad outline of the trial aim, results and conclusions sufficed") suggest they realised that most of these studies were either multicentre or single centre RCTs with only subtle and forgettable variations in their design. As such, details of the methods are omitted from the list below.

• MENDS - 2007- dex vs. lorazepam, n=106 in the US. Preposterous mortality difference (17% vs 27%) in favour of dex.
• DEX-COM - 2009 - dex vs. morphine in the wealthy Eastern suburbs of Sydney; n = 306 CABG patients. Delirium incidence was the same, but duration was shorter with dex (2 vs 5 days).
• MIDEX-PRODEX - 2012 - dex vs prop or midaz (actually two trials). n=500 and 501, in Europe. Shorter duration of ventilation vs. midazolam, but not vs. propofol. Otherise not inferior to the other agents.
• DahLIA - 2016 - dex vs. placebo, looking at delirium and ventilator-free time over 7 days. n=71 in Australia and NZ. The dex group spent about 17 hours less on the ventilator, and their delirium resolved faster (23 vs 40 hours).
• Xian Su - 2016 - dex, but in elderly post-op patients? n=700 elective surgical patients in China, only over-65s. Greatly reduced incidence of delirium (9% vs 23%) and ICU stay (20.9 vs 21.5 hrs) but basically all of the patients only stayed in the ICU overnight, so.. is this really the population that needs sophisticated delirium prevention techniques?
• DESIRE - 2017 - dex plus whatever other agents, vs. sedation without dex, looking at 28-day mortality. n=201 in Japan. No difference in mortality or ventilator-free days.
• Skrobik et al - 2018 - dex at low dose (02-0.7 mcg/kg/hr), overnight, to improve sleep. n=100 in Canada and USA. Risk of delirium greatly reduced (54% vs 80%), as well as time to extubation and length of ICU stay, 
• SPICE-III - 2019 - dex as the sole agent, vs. all others, looking at 90-day mortality. n=4000, all over the world. No difference in mortality (31.5% vs 31.3%); and they weirdly expected a mortality difference of 4.4%. There was one extra ventilator-free day with dex.
• MENDS2 - 2021 - dex vs propofol. n=438, in the US. None of the patients received much of either drug, and unsurprisingly there were no differences in any of the outcomes.

Sessler, Curtis N., et al. "The Richmond Agitation–Sedation Scale: validity and reliability in adult intensive care unit patients." American journal of respiratory and critical care medicine 166.10 (2002): 1338-1344.

Sessler, Curtis N., Mary Jo Grap, and Gretchen M. Brophy. "Multidisciplinary management of sedation and analgesia in critical care." Seminars in respiratory and critical care medicine. Vol. 22. No. 02. Copyright© 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.:+ 1 (212) 584-4662, 2001.

Sessler, Curtis N., and Kim Keane. "Validity and reliability of a new agitation-sedation scale in a medical ICU population." Chest 118.4 (2000): 95S-95S.

Almgren, M., M. Lundmark, and Karin Samuelson. "The Richmond Agitation‐Sedation Scale: translation and reliability testing in a Swedish intensive care unit." Acta anaesthesiologica scandinavica 54.6 (2010): 729-735.