How does dexmedetomidine compare to antipsychotics for the management of delirium in the ICU?

Comment by InpharmD Researcher

Limited data directly compares dexmedetomidine to antipsychotics for the management of delirium in the ICU. The 2018 Society of Critical Care Medicine’s Clinical Practice Guidelines recommend against routine use of haloperidol and atypical antipsychotics in the treatment of delirium but provide conditional recommendations for dexmedetomidine in mechanically ventilated adults with delirium. A recent meta-analysis demonstrated the superiority of dexmedetomidine to ziprasidone and risperidone in active treatment, whereas quetiapine led to a better response rate than dexmedetomidine compared to other antipsychotics; however, the findings may be limited by the heterogeneity among studies. The lack of head-to-head comparative trials makes it difficult to provide a comprehensive comparison with other commonly used antipsychotics for this indication.
Background

Per the 2018 Society of Critical Care Medicine’s Clinical Practice Guidelines, the panel recommends against using haloperidol, an atypical antipsychotic, dexmedetomidine, a β-Hydroxy β-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitor, or ketamine to prevent delirium in all critically ill adults (conditional recommendation, very low to low quality of evidence). Additionally, routine use of haloperidol, an atypical antipsychotic, or an HMG-CoA reductase inhibitor should be avoided for the treatment of delirium. On the other hand, dexmedetomidine may be considered in mechanically ventilated adults with delirium where agitation precludes weaning/extubation (conditional recommendation, low quality of evidence). Of note, the recommendation for dexmedetomidine is based on a single placebo-controlled randomized trial; thus, there is no direct comparison with antipsychotics in this setting. [1]

A 2020 meta-analysis compared the efficacy and safety of dexmedetomidine and other agents for the management of delirium, with sub-analyses available specifically for the intensive care unit (ICU) setting. A total of 108 randomized controlled studies were included for analysis, with 24 (n= 1,846) focusing on treatment and 84 (n= 28,089) focusing on prevention. For treatment in ICU patients, the response rate for dexmedetomidine had an odds ratio (OR) of 2.66 (95% confidence interval [CI] 1.05 to 6.77). When compared to antipsychotics, quetiapine surpassed dexmedetomidine in OR, but the confidence interval was widely distributed, indicating possible heterogeneity within the studies (OR 8.00; 95% CI 1.41 to 45.41). Dexmedetomidine demonstrated a higher OR compared to lorazepam (OR 2.03), ziprasidone (OR 1.23) ondansetron (OR 1.25), haloperidol (OR 1.01), rivastigmine (OR 0.87), and midazolam (OR 0.28). [2]

For prevention of delirium in ICU surgical patients, dexmedetomidine reported an OR of 0.46 (95% CI 0.32 to 0.66), which favors the active drug. Only risperidone, combination diazepam/flunitrazepam/pethidine, and combination dexmedetomidine/acetaminophen report lower ORs compared to dexmedetomidine. For prevention of delirium in ICU medical patients, dexmedetomidine (OR 0.50; 95% CI 0.04 to 6.30) was only surpassed by trazodone, ramelteon, and suvorexant, although there were noticeably fewer antipsychotics for comparison. The quality of studies reporting on dexmedetomidine is generally rated moderate to high. Despite the perceived benefit of reducing delirium in the ICU setting, dexmedetomidine also observed a higher dropout rate which questions the tolerability of adverse events. Yet the authors also do not suggest routine use of antipsychotics and have established a preference for dexmedetomidine. [2]

A 2019 review discussing the use of dexmedetomidine in the management of delirium in intensive care units noted a favorable safety profile of dexmedetomidine compared to that of antipsychotics (QTc prolongation, extrapyramidal effects, and sedation). Other outstanding differentiating features included sedative effects without respiratory depression and reduced need for benzodiazepines. Despite the lack of supporting clinical data, the authors proposed these superior qualities of dexmedetomidine over antipsychotic medications in the management of delirium. [3]

Several reviews evaluated studies that compared the role of dexmedetomidine with other sedatives, analgesics, or antipsychotics for the prevention and treatment of delirium in ICU patients. A randomized, open-label, parallel-group pilot study that compared the effect of dexmedetomidine with haloperidol in the treatment of ICU delirium is commonly referred to when evaluating the effect of dexmedetomidine versus other antipsychotics. Dexmedetomidine, in comparison with haloperidol, significantly shortened the median time to extubation (19.9 vs. 42.5 hours; p= 0.016) and decreased median ICU length of stay (1.5 vs. 6.5 days; p= 0.004) in mechanically ventilated patients (Table 1). Based on the findings from this study, it was suggested that dexmedetomidine might be an effective agent in the treatment of ICU-associated delirium agitation. [4-6]

A 2020 review evaluated data from 10 systematic reviews on the pharmacological treatment of delirium in both intensive and non-intensive care settings to provide treatment alternatives to haloperidol or other standards of care in patients with COVID-19. Only quetiapine and dexmedetomidine demonstrated possible benefits in ICU settings among all antipsychotics, benzodiazepines, and other pharmacological agents being evaluated. However, a direct comparison between quetiapine and dexmedetomidine was not provided, and the overall quality of evidence remained low. [7,8]

A 2019 meta-analysis attempted to discern the best pharmacologic intervention for the management and prevention of delirium, non-specific to the ICU. A total of 58 studies were included for analysis (20 were treatment for delirium while 38 were preventative for delirium). A subanalysis of ICU patients was not performed. The OR for a treatment response favoring dexmedetomidine versus placebo/control was 2.06 (95% CI 0.51 to 8.34), which was surpassed by other antipsychotic agents, including haloperidol, olanzapine, ziprasidone, and quetiapine but not surpassed by risperidone or haloperidol+rivastigmine. For prevention, dexmedetomidine reported a lower delirium occurrence rate compared to placebo/control (OR 0.50; 95% CI 0.31 to 0.80), which was surpassed by risperidone and olanzapine but not surpassed by haloperidol and midazolam. Using surface under the cumulative ranking curve (SUCRA) to compare the outcomes with an optimally imaginative intervention, dexmedetomidine and midazolam are considered the most effective preventative regimens while associated with the least increase in overall mortality. Ramelteon is still considered the most effective prophylactic agent (OR 0.07; 95% CI 0.01 to 0.66), while haloperidol+lorazepam may be the most effective treatment regimen (OR 28.13; 2.38 to 333.08). The included trials were characterized by underpowered statistics and heterogeneity among baseline characteristics. While the results favor ramelteon, the majority of evidence was published by a single network of investigators. [9]

References:

[1] Devlin JW, Skrobik Y, Gélinas C, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. doi:10.1097/CCM.0000000000003299
[2] Kim MS, Rhim HC, Park A, et al. Comparative efficacy and acceptability of pharmacological interventions for the treatment and prevention of delirium: A systematic review and network meta-analysis. J Psychiatr Res. 2020;125:164-176. doi:10.1016/j.jpsychires.2020.03.012
[3] Ungarian J, Rankin JA, Then KL. Delirium in the Intensive Care Unit: Is Dexmedetomidine Effective?. Crit Care Nurse. 2019;39(4):e8-e21. doi:10.4037/ccn2019591
[4] Serafim RB, Bozza FA, Soares M, et al. Pharmacologic prevention and treatment of delirium in intensive care patients: A systematic review. J Crit Care. 2015;30(4):799-807. doi:10.1016/j.jcrc.2015.04.005
[5] McLaughlin M, Marik PE. Dexmedetomidine and delirium in the ICU. Ann Transl Med 2016;4(11):224. doi:10.21037/atm.2016.05.44
[6] Mo Y, Zimmermann AE. Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients. Ann Pharmacother. 2013;47(6):869-876. doi:10.1345/aph.1AR708
[7] Ostuzzi G, Gastaldon C, Papola D, et al. Pharmacological treatment of hyperactive delirium in people with COVID-19: rethinking conventional approaches. Ther Adv Psychopharmacol. 2020;10:2045125320942703. Published 2020 Jul 20. doi:10.1177/2045125320942703
[8] Burry LD, Cheng W, Williamson DR, et al. Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis. Intensive Care Med. 2021;47(9):943-960. doi:10.1007/s00134-021-06490-3
[9] Wu YC, Tseng PT, Tu YK, et al. Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis. JAMA Psychiatry. 2019;76(5):526-535. doi:10.1001/jamapsychiatry.2018.4365

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

How does dexmedetomidine compare to antipsychotics for the management of delirium in the ICU?

Level of evidence

A - Multiple high-quality studies with consistent results  Read more→



Please see Tables 1-3 for your response.


 

Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial

Design

Randomized, open-label, parallel-group, pilot trial

N= 20

Objective

To compare the efficacy of haloperidol and dexmedetomidine in facilitating extubation in patients with agitated delirium undergoing mechanical ventilation

Study Groups

Dexmedetomidine (n= 10)

Haloperidol (n= 10)

Inclusion Criteria

Patients admitted to the intensive care unit (ICU) for agitation and delirium undergoing mechanical ventilation only because their degree of agitation required such high doses of sedative medication that extubation was not possible

Exclusion Criteria

Could not be extubated despite management of agitation, adverse reaction to haloperidol or alpha-2 agonists

Methods

Patients were randomized to receive either haloperidol intravenous (IV) loading dose 2.5 mg (if desired) followed by continuous IV infusion 0.5 to 2 mg/hour or dexmedetomidine loading dose of 1.0 mcg/kg IV over 20 minutes (if desired) followed by continuous IV infusion of 0.2 to 0.7 mcg/kg/hour. Treatment lasts for as long as the attending physician deems necessary. Bedside nurses reassessed every 4 hours to alter the rate of infusion with the goal of minimizing psychomotor agitation and achieving a Richmond Agitation Sedation Scale (RASS) of 0. Haloperidol could be reinitiated without restriction, but dexmedetomidine could not be restarted once stopped due to not being on the hospital formulary. Any additional sedatives or anxiolytic medications were allowed.

Duration

Until extubated

Outcome Measures

Primary: time to extubation

Secondary: characteristics of study drug use, time to ICU discharge after randomization, ICU length of stay, time to achieve RASS agitation score -2 to 1

Baseline Characteristics

 

Dexmedetomidine (n= 10)

Haloperidol (n= 10)

 

Median age, years

52 68.5  

Males

90% 80%  

Median APACHE II score 24 hours immediately prior to enrollment

13.3 15.5  

Patient characteristics

Physical restraint prior to enrollment

Midazolam use

Propofol use

Haloperidol use

Morphine use

Other sedative or antipsychotic use

 

8

6

7

3

8

0

 

5

4

7

1

8

0

 

Results

Endpoint

Dexmedetomidine (n= 10)

Haloperidol (n= 10)

p-value

Median time to extubation, hours (interquartile range [IQR])

19.9 (7.3 to 24.0) 42.2 (23.2 to 117.8) 0.016

Received loading dose of study drug

8 6 0.329

Drug rate of infusion, (95% confidence interval [CI])

0.47 (0.33 to 0.62)

mcg/kg/hour

1.43 (0.96 to 1.90)

mg/hour

N/A

Study drug continued after extubation

Length of continuation, hours (IQR)

7

2.5 (0.0 to 26.0)

4

0.0 (0.0 to 2.0)

0.18

0.15

Median time to ICU discharge, days (IQR)

Median total ICU length of stay, days (IQR)

1.5 (1 to 3)

4.5 (2 to 7)

6.5 (4 to 9)

8.0 (7 to 11)

0.0039

0.0093

Median time to achieve RASS agitation score -2 to 1, hours (IQR)

4 (0 to 7)

18 (9 to 22)

0.071

Percent time that patients required propofol sedation (95% CI)

41.2% (0 to 88.2%)

79.5% (61.8% to 97.2%)

0.05

Adverse Events

Arrhythmia occurred in 2 patients in each group. QTc prolongation was not significantly different, but the haloperidol trended towards longer intervals. No adverse events were deemed related to dexmedetomidine, whereas excessive QTc prolongation was attributed to haloperidol use in 1 patient, leading to treatment discontinuation. Eight patients in the dexmedetomidine group required norepinephrine.

No deaths occurred in the ICU. One patient in the haloperidol group died in the general ward due to an underlying disease.

Study Author Conclusions

In this preliminary pilot study, we found dexmedetomidine a promising agent for the treatment of ICU-associated delirious agitation, and we suggest this warrants further testing in a definitive double-blind multi-center trial.

InpharmD Researcher Critique

Pilot studies have inherent limitations that require follow-up in quality, controlled studies to verify their findings. Other treatment strategies allowed by the attending physicians were uncontrolled. The small number of patients included, and the short follow-up duration may not be enough to provide meaningful data.



References:

Reade MC, O'Sullivan K, Bates S, Goldsmith D, Ainslie WR, Bellomo R. Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial. Crit Care. 2009;13(3):R75. doi: 10.1186/cc7890. Epub 2009 May 19. PMID: 19454032; PMCID: PMC2717438.

 

Dexmedetomidine for the Treatment of Hyperactive Delirium Refractory to Haloperidol in Nonintubated ICU Patients: A Nonrandomized Controlled Trial

Design

Single-center, non-randomized, prospective, controlled trial

N= 132

Objective

To evaluate the clinical effectiveness, safety, and cost of dexmedetomidine for the treatment of agitated delirium refractory to haloperidol in non-intubated critically ill patients

Study Groups

Dexmedetomidine (n= 46)

Haloperidol (n= 86)

Inclusion Criteria

Age between 18 to 95 years; admitted to the intensive care unit (ICU) for agitated delirium; Richmond Agitation Sedation Scale (RASS) storage of +1 to +4; acute onset and fluctuating course of mental disturbance; altered level of consciousness as evaluated with the confusion assessment method for the ICU (CAM-ICU); Intensive Care Delirium Screening Checklist (ICDSC)

Exclusion Criteria

Intubation; non-invasive ventilation; pregnancy; previous diagnosis of psychopathic disorder or history of substance abuse; administration of antipsychotic medication in the 10 days prior to enrollment; contraindication to haloperidol or dexmedetomidine; neurologic condition that did not allow neuropsychiatric evaluation

Methods

All patients received haloperidol intravenous (IV) bolus 2.5 to 5 mg at 10 to 30-minute intervals until control of agitation was achieved (RASS 0 to -2) or until reaching the max cumulative daily dose of 30 mg. Patients were classified as responders (RASS 0 to -3) or non-responders (RASS +1 to +4). The responders received haloperidol infusion of 0.5 to 1.0 mg/hour adjusted as necessary to achieve a RASS of 0. In contrast, non-responders received dexmedetomidine rescue infusion at 0.2 mcg/kg/hour to achieve a RASS of 0.

Groups began comparison once all patients achieved a RASS score of 0. All patients received IV acetaminophen every 8 hours. Nurses may administer additional analgesics as necessary. 

Duration

December 31, 2013, through December 31, 2014

Outcome Measures

Primary efficacy: quality of sedation (defined as the percentage of time that the patient was maintained at RASS score 0 to -2 and ICDSC < 4)

Primary safety: excessive sedation (RASS score -3 to -5)

Secondary: Time under ICDSC score < 4, attempt at removal of physical constraints during treatment, additional analgesics utilized, ICDSC score of 0 to 1 at discharge

Baseline Characteristics

 

Dexmedetomidine (n= 46)

Haloperidol (n= 86)

p-value

Age, years

70.3 ± 12.5 71.3 ± 11.3 0.64

Male

37 77 0.49

Acute Physiology and Chronic Health Evaluation II score in the 24 hours immediately prior to initial haloperidol titration

15.3 ± 6.0 15.5 ± 7.3 0.87

Admission diagnosis

Sepsis

Cardiothoracic surgery

Abdominal surgery

Other

 

5

11

19

11

 

15

18

34

19

 

0.08

0.97

0.57

0.97

RASS (18) score at diagnosis of delirium

3.9 ± 1.8 3.1 ± 1.3 0.75

Physical restraint prior to haloperidol titration

12 21 0.83

Results

Endpoint

Dexmedetomidine (n= 46)

Haloperidol (n= 86)

p-value

Percent of time under sedation between RASS score 0 to -2 (95% confidence interval [CI])

92.7% (84.5% to 99.8%)

59.3% (49.1% to 78.0%)

0.0001

Excessive sedation (RASS -3 to -5) requiring discontinuation of treatment (95% CI)

0

10 (11.6%; 6.5 to 21.2)

0.01

Percentage of time under ICDSC score < 4 (95% CI)

52.0 (37.5% to 66.4%)

29.5 (13.0% to 42.3%)

0.005

Removal of physical restraint during treatment (95% CI)

97.8% (92.0% to 100%)

93.1% (87.6% to 98.3%)

0.11

Dose of additional analgesic, mg/kg/day (95% CI)

Acetaminophen

Metamizol

Morphine

 

20.8 ± 5.3

28.5 ± 7.1

0.10 ± 0.05

 

21.7 ± 7.8

80.3 ± 8.3

0.60 ± 0.21

 

0.15

< 0.001

< 0.0001

ICDSC score of 0 to 1 at ICU discharge

100%

100%

--

Safety outcomes

Abnormal corrected for heart rate QT interval (> 0.44 sg)

Supraventricular arrhythmia

Ventricular arrhythmia

Atrioventricular block

Bradycardia requiring treatment

Maintained mean arterial hypotension (< 70 mmHg)

Requiring new norepinephrine infusion

ICU mortality

Hospital mortality

 

0

12 (26.0%)

0

0

5 (10.8%)

6 (13.0%)

4 (8.6%)

0

4 (8.6%)

 

2 (2.3%)

24 (27.8%)

0

0

4 (4.6%)

18 (20.9%)

11 (12.7%)

2 (2.3%)

7 (8.1%)

 

0.69

0.52

--

--

0.21

0.34

0.31

0.69

0.09

Adverse Events

See above

Study Author Conclusions

In the study conditions, dexmedetomidine shows to be useful as a rescue drug for treating agitation due to delirium in non-intubated patients in whom haloperidol has failed, and it seems to have better effectiveness, safety, and cost-benefit profile than haloperidol.

InpharmD Researcher Critique

This was an unblinded study without randomization that specifically focused on patients with agitated delirium. This would exclude patients with hypoactive delirium who can also present with agitation. Patients who experienced oversedation or OTc prolongation were excluded from analysis, which limits real-world applicability.



References:

Carrasco G, Baeza N, Cabré L, Portillo E, Gimeno G, Manzanedo D, Calizaya M. Dexmedetomidine for the Treatment of Hyperactive Delirium Refractory to Haloperidol in Nonintubated ICU Patients: A Nonrandomized Controlled Trial. Crit Care Med. 2016 Jul;44(7):1295-306. doi: 10.1097/CCM.0000000000001622. PMID: 26925523.

 

Are dexmedetomidine and olanzapine suitable to control delirium in critically ill elderly patients? A retrospective cohort study

Design

Retrospective, cohort study

N= 263

Objective

To evaluate the efficacy and safety of dexmedetomidine and olanzapine for delirium control in critically ill elderly patients without ventilation or surgery 

Study Groups

Dexmedetomidine (n=118)

Olanzapine (n= 145)

Inclusion Criteria

Aged ≥ 75 years old, met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria of the American Psychiatric Association, and provided telephone-informed authorization consent from survivors or family members

Exclusion Criteria

Endotracheal ventilation, underwent surgery during the hospital stay, advanced-stage tumors, brain tumors, or recent brain trauma, underwent blood purification therapy during the use of olanzapine or dexmedetomidine, curative effects and adverse effects that could not be evaluated because of incomplete data and uniform evaluation criteria

Methods

Patients' charts were retrospectively reviewed to identify eligible subjects who were admitted to the intensive care unit (ICU) and treated with intravenous dexmedetomidine and oral olanzapine. Delirium was detected by utilizing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). The diagnosis of delirium was further confirmed by a neurologist using DSM-5, and a blinded examiner evaluated the severity of delirium using the Delirium Rating Scale Revised 98 (DRS-98). 

Dexmedetomidine was initiated at a dose of 0.1 mcg/kg/hour with a Richmond Agitation-Sedation Scale (RASS) goal of 0 to −2 during the daytime and a score of  −1 to −3 during the nocturnal period. The infusion rate was increased or decreased by 0.1 mcg/kg/hour every 15 min when the RASS score was out of range with a maximum rate of 0.7 mcg/kg/hour. The infusion was stopped every morning to evaluate the patient's status and occurrence of delirium. Olanzapine was administered orally or via a nasogastric tube at a dose of 2.5 mg/day to patients with dementia and 5 mg/day for those without dementia with dose adjustment every 24 hours. When delirium or the inducing factor of delirium disappeared, the dose of olanzapine was gradually decreased (1/2 to 1/4 a day). To compare the prognosis of ICU patients between the two groups, the rate of endotracheal intubation, mortality rate, length of hospital stay, long-term cognitive functions, and recurrence of delirium was recorded within three months in survivors. 

Duration

Enrollment period: April 2014 to April 2020

Follow-up: 3 months

Outcome Measures

Effects of dexmedetomidine and olanzapine on delirium control and prognosis of ICU patients, adverse effects

Baseline Characteristics

 

Dexmedetomidine (n= 118)

Olanzapine (n= 145)

 

Age, years

80.05 78.99  

Male

81.36% 73.10%  

Smoke

16.10% 34.14%  

Anxiety/depression 

3.39%  5.52%  

CVD associated with delirium

9.32% 11.34%  

CAD

13.56% 21.38%  

Normal cognitive function

41.53% 44.14%  

Dementia

10.17% 11.03%  

Delirium before treatment

17.80% 15.17%  

APACHE II score within 24 hours after ICU admission

18.91 ± 4.22 18.59 ± 4.56  

CAM-ICU score

28.17 ± 3.80 28.35 ± 5.37  

DRS-98 score

20.26 ± 2.67 20.65 ± 3.20  

CVD: cerebral vascular disease; CAD: coronary artery disease; APACHE: Acute Physiology and Chronic Health Evaluation Score

Results

Endpoint

Dexmedetomidine (n= 118)

Olanzapine (n= 145)

p-value

Average maximum RASS score

1.61 ± 1.56 2.70 ± 1.01 < 0.001

Mean RASS score

-0.57 ± 0.88 

0.88 ± 0.73 < 0.001

Average minimum RASS score

-1.67 ± 1.04 -1.37 ± 1.01 0.014

Drug use duration, days

4.83 ± 2.67 5.87 ± 3.14 0.005

Intubation during drug use

27 (22.88%) 18 (12.41%) 0.023

Inclusion of additional sedatives

Lytic mixture, times

Diazepam, times

Midazolam, times

Dexmedetomidine, times

16 (13.56%)

2/16 (12.5%)

4/16 (25%)

10/16 (62.5%) 

0/16

58 (40%)

22/58 (37.93%)

3/58 (5.17%)

19/58 (32.76%)

14/58 (24.14%)

0.003

Mortality

29 (24.58%) 31 (21.37%) 0.336

Length of hospital stay, days

9.30 ± 4.90 8.83 ± 3.34 < 0.001

Long-term cognitive function

No change

Decrease

Death

 

43 (36.44%)

28 (23.73%)

36 (30.51%)

 

54 (37.24%) 

44 (30.34%)

36 (24.83%)

0.678

Recurrence of delirium

Nonrecurrence

Recurrence

Death

Lost to follow-up

 

42 (35.59%)

32 (27.12%)

36 (30.51%)

8 (6.78%)

 

47 (32.41%) 

53 (36.55%)

36 (24.83%)

9 (6.21%)

0.426

Adverse effects

Respiratory depression 20 (16.95%) 3 (2.84%) <0.001
Hypoxia 16 (13.56%) 3 (2.76%) <0.001
Hypotension 13 (11.02%) 4 (3.45%) 0.007
Tachycardia 7 (5.93%) 0.053
Bradycardia 1 (0.85%) 0.267
Coma 3 (2.54%) 1 (0.01%) 0.222
Extrapyramidal side effects 0 2 (1.38%) 0.200

Adverse Events

See results. 

Study Author Conclusions

Dexmedetomidine achieved a more satisfactory sedative effect on delirium control in critically ill patients without surgery and ventilation but resulted in a higher rate of adverse effects. Age, severe cardiopulmonary disease, APACHE II scores, dexmedetomidine dose, minimum RASS score, and sedative combinations were significantly associated with relatively higher rates of adverse effects of dexmedetomidine. Olanzapine was safer in high-risk patients with a critical illnesses.

InpharmD Researcher Critique

The study is subject to limitations and biases inherent to its small sample size, retrospective, and single-center design. Additionally, the degree of delirium onset and sedation score during the administration of olanzapine alone was not regularly recorded, and the evaluation of DRS-98 and RASS scores of the olanzapine group according to the patients' medical records and nursing records may have led to an imprecise evaluation. 



References:

Liu S, Zhao R, Yang R, et al. Are dexmedetomidine and olanzapine suitable to control delirium in critically ill elderly patients? A retrospective cohort study. Biomed Pharmacother. 2021;139:111617. doi:10.1016/j.biopha.2021.111617