Please create a comparative dose-equivalency table for sedative effect across agents and classes for common ICU sedatives in mechanically ventilated patients.

Comment by InpharmD Researcher

Based on our literature search, comparative data for sedatives and their therapeutic effects appears to be scattered and insufficient to provide an accurate and definitive yet broad comparison between agents and classes. Accordingly, due to the scattered data, exact dose equivalency was not unsupported by the available literature. Still, while utilizing applicable references, a table was created to compile any available comparative data between sedatives based on various sedation scales, including RASS and Ramsay. Please refer to Table 1 for information on the numerous product comparisons we were able to identify. No studies in the identified literature directly compared hydromorphone or morphine (as primary sedatives) with ketamine using RASS or SAS as the primary endpoint.

Background

The 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium (and subsequently, the 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disturbances guidelines) established a target light sedation goal for most adult ICU patients, defined as a Richmond-Agitation Sedation Scale (RASS) score of 0 to -2 or a Sedation Agitation Scale (SAS) score of 3 to 4. Targeting lighter sedation levels has been linked to improved clinical outcomes (e.g., shorter duration of mechanical ventilation and shorter ICU length of stay). For light sedation, non-benzodiazepine sedatives (e.g., propofol, dexmedetomidine) are recommended over benzodiazepines given the deliriogenic potential of continuous benzodiazepine infusions, but mention of exact effective doses is not provided. The guidelines provide loading and maintenance doses for these sedative agents (Table 2) but fail to provide equivalent dosing recommendations to achieve target sedation levels because this is an individualized target for titration with wide inter-patient variability. It is instead suggested to determine choice of sedative agent using drug-specific factors (e.g., onset of action, half-life, adverse effect profiles, ability to achieve various levels of sedation), patient-specific factors (e.g., hemodynamics especially blood pressure and heart rate, need for mechanical ventilation), and indication for sedation (e.g., need for deep sedation vs light sedation). The guidelines recommend benzodiazepines or propofol if deep sedation is indicated, defined as RASS score of -4 to -5 or SAS score of 1 to 2, but otherwise do not make recommendations on dose equivalency to achieve sedation targets. [1], [2]

Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

Please create a comparative dose-equivalency table for sedative effect across agents and classes for common ICU sedatives in mechanically ventilated patients.

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-6 for your response.

Comparative Sedative Effect Across Agents
Drug	Drug Class	Dose Used in Study	Sedation Scale	Sedation Result / Score	Comparator	Sample size	Population & Source
Dexmedetomidine	Alpha-2 agonist	0.25 mcg/kg/hr infusion	Ramsay; PICU Sedation Score; BIS	Mean Ramsay 3.7±1.1; PICU score 3.1±0.9; BIS 51±12 — comparable to midazolam (all p=NS)	Midazolam ~0.22 mg/kg/hr	10	Pediatric MV, Tobias et al. 2004
		0.5 mcg/kg/hr infusion	Ramsay; PICU Sedation Score; BIS	Mean Ramsay 3.5±0.8; PICU score 2.9±1.1; BIS 60±10 — fewer morphine boluses vs midazolam (p=0.02); reduced 24-hr morphine (p=0.01)	Midazolam ~0.22 mg/kg/hr	10	Pediatric MV, Tobias et al. 2004
		0.2–1.4 mcg/kg/hr	RASS (target −2 to +1)	77.3% time in target RASS range; delirium 54% vs 76.6% (p<0.001); extubation 3.7 vs 5.6 days (p=0.01)	Midazolam 0.02–0.1 mg/kg/hr	244	Adult MV, Riker et al. 2009
		Starting 0.25 mcg/kg/hr; titrated per PSCH algorithm	PSCH Sedation Algorithm (target level 4–5)	56.5±28.6% time in target range; sedation duration 26 h (IQR 14–48) — non-inferiority vs midazolam NOT established	Midazolam 1 mcg/kg/min	23	Pediatric MV, Gulla et al. 2021
		0.2–1.5 mcg/kg/hr; median 0.27 mcg/kg/hr	RASS (target 0 to −2); primary outcome: days alive without delirium/coma	Median RASS −2.0; days alive w/o delirium/coma: adj. median 10.7 days; ~57% time at target; OR 0.96 (95% CI 0.74–1.26, p=0.79) — equivalent to propofol	Propofol 5–50 mcg/kg/min; median 10.2 mcg/kg/min	214	Adult MV with sepsis, Hughes et al. 2021
Midazolam	Benzodiazepine	Starting 0.1 mg/kg/hr; titrated	Ramsay; PICU Sedation Score; BIS	Mean Ramsay 3.6±0.9; PICU score 2.9±1.2; BIS 57±8 — comparable to both dexmedetomidine doses	Dexmedetomidine 0.25 and 0.5 mcg/kg/hr	10	Pediatric MV, Tobias et al. 2004
		0.02–0.1 mg/kg/hr	RASS (target −2 to +1)	75.1% time in target RASS range (p=0.18 vs dexmedetomidine); delirium 76.6%; extubation 5.6 days	Dexmedetomidine 0.2–1.4 mcg/kg/hr	122	Adult MV, Riker et al. 2009
		Starting 1 mcg/kg/min; titrated per PSCH algorithm	PSCH Sedation Algorithm (target level 4–5)	67.3±18.8% time in target range; sedation duration 53 h (IQR 31–83.5, p=0.014 vs dexmedetomidine)	Dexmedetomidine 0.25 mcg/kg/hr	24	Pediatric MV, Gulla et al. 2021
Propofol	Alkylphenol (anesthetic)	Per clinical guidelines (ICU-specific)	RASS (twice daily)	RASS vs. interval dose: r=−0.46 (p<0.001); RASS vs. plasma conc.: r=−0.18 (p=0.07, NS) — dose-effect relationship weakest of the three agents	Fentanyl and lorazepam (observational)	18	Adult MV (ICU), Masica et al. 2007
		5–50 mcg/kg/min; median 10.2 mcg/kg/min	RASS (target 0 to −2); primary outcome: days alive without delirium/coma	Median RASS −1.95; days alive w/o delirium/coma: adj. median 10.8 days; ~60% time at target — no difference vs dexmedetomidine	Dexmedetomidine 0.2–1.5 mcg/kg/hr; median 0.27 mcg/kg/hr	208	Adult MV with sepsis, Hughes et al. 2021
		Starting 2.0 mg/kg/hr; max 4.0 mg/kg/hr; median 1.98 mg/kg/hr	RASS (target −3 to 0)	82.8% time in target RASS range (IQR 65.6–100%); 69.3% of individual RASS observations in range — no difference vs remimazolam (p=0.269)	Remimazolam besylate 0.15–0.3 mg/kg/hr	30	Adult MV, Tang et al. 2022
Remimazolam besylate	Benzodiazepine (ultra-short-acting)	Starting 0.15 mg/kg/hr; max 0.3 mg/kg/hr; median 0.18 mg/kg/hr	RASS (target −3 to 0)	73.2% time in target RASS range (IQR 41.5–97.3%); 67.8% of individual RASS observations in range — no difference vs propofol (p=0.269)	Propofol 2.0–4.0 mg/kg/hr	30	Adult MV. Tang et al. 2022
Lorazepam	Benzodiazepine	Per clinical guidelines (ICU-specific)	RASS (twice daily)	RASS vs. interval dose: r=−0.28 (p=0.001); RASS vs. plasma conc.: r=−0.49 (p<0.001) — moderate correlation	Fentanyl and propofol (observational)	18	Adult MV (ICU), Masica et al. 2007
Fentanyl	Opioid	Per clinical guidelines (ICU-specific)	RASS (twice daily)	RASS vs. interval dose: r=−0.39 (p=0.002); RASS vs. plasma conc.: r=−0.46 (p=0.002) — moderate correlation	Lorazepam and propofol (observational)	18	Adult MV (ICU), Masica et al. 2007
RASS = Richmond Agitation-Sedation Scale; PICU = Pediatric ICU; PSCH = Penn State Children's Hospital; BIS = Bispectral Index; MV = mechanical ventilation.

References:
[1] [1] Tobias JD, Berkenbosch JW. Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J. 2004;97(5):451-455.
[2] [2] Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489-499.
[3] [3] Gulla KM, Sankar J, Jat KR, Kabra SK, Lodha R. Dexmedetomidine vs Midazolam for Sedation in Mechanically Ventilated Children: A Randomized Controlled Trial. Indian Pediatr. 2021;58(2):117-122.
[4] [4] Masica AL, Girard TD, Wilkinson GR, et al. Clinical sedation scores as indicators of sedative and analgesic drug exposure in intensive care unit patients. Am J Geriatr Pharmacother. 2007;5(3):218-231.
[5] [5] Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis (MENDS2). N Engl J Med. 2021;384(15):1424-1436.
[6] [6] Tang Y, Yang X, Yu Y, et al. Remimazolam besylate versus propofol for long-term sedation during invasive mechanical ventilation: a pilot study. Critical Care. 2022;26:279.

Clinical pharmacology of sedative medications
Agent	Time to onset after IV loading dose	Elimination half-life	Loading dose (IV)	Maintenance dosing (IV)
Midazolam	2-5 minutes	3-11 hours	0.01-0.05 mg/kg	0.02-0.1 mg/kg/hour
Lorazepam	15-20 minutes	8-15 hours	0.02-0.04 mg/kg (≤2 mg)	0.02-0.06 mg/kg q2-6h PRN or 0.01-0.1 mg/kg/hour (≤10 mg/hour)
Propofol	1-2 minutes	3-12 hours (short-term) 50 ± 18.6 hours (long-term)	5 mcg/kg/minute	5-50 mcg/kg/minute
Dexmedetomidine	5-10 minutes	1.8-3.1 hours	1 mcg/kg	0.2-0.7 mcg/kg/hour

References:
[1] [1] Barr J, Fraser GL, Puntillo K, et al; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. doi:10.1097/CCM.0b013e3182783b72

Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam
Design	Prospective, randomized trial in a pediatric intensive care unit (PICU) at a tertiary care center N=30
Objective	To compare the efficacy of midazolam vs dexmedetomidine for sedation during mechanical ventilation in infants and children
Study Groups	Midazolam (n=10) Dexmedetomidine 0.25 mcg/kg/hr (n=10) Dexemdetomidine 0.5 mcg/kg/hr (n=10)
Inclusion Criteria	Patients admitted to PICU who required mechanical ventilation
Exclusion Criteria	Patients with pre-existing central nervous system dysfunction or acquired conditions resulting in ongoing dysfunction
Methods	Following endotracheal intubation and prior to randomization, sedation was provided by intermittent midazolam 0.1 mg/kg/hr as needed. Patients were randomized to either midazolam (starting at 0.1 mg/kg/hr) or dexmedetomidine (starting at either 0.25 mcg/kg/hr or 0.5 mg/kg/hr). Boluses of the corresponding study drug were given if initial sedation deemed inadequate. After sedative infusions were started, additional sedation was provided by intermittent morphine 0.08-0.1 mg/kg/hr boluses as needed. If >3-4 morphine doses were needed over a 8-hour period, study drug infusion rates were increased (midazolam by 0.05-0.1 mg/kg/hr and dexmedetomidine by 0.15-0.25 mcg/kg/hr) after administration of a bolus of the study drug. If ongoing mechanical ventilation was needed after 24 hours, the patient was switched to the alternative agent. Quality of sedation was assesed every 2 hours using 3 clinical scales and the Bispectral Index (BIS) Monitor. Ramsay sedation scale PICU sedation score Tracheal suctioning score
Duration	Not specified
Outcome Measures	Morphine boluses administered Total morphine use (mg/kg/day) Inadequate sedation (Ramsay score = 1)
Baseline Characteristics		Midazolam (n=10)	Dexmedetomidine 0.25 mcg/kg/hr (n=10)	Dexmedetomidine 0.5 mcg/kg/hr (n=10)	p-value
	Mean age, months	36 ± 34	44 ± 54	39 ± 44	NS
	Mean weight	19 ± 20	22 ± 27	21 ± 24	NS
	Female sex, n (%)	4 (40%)	3 (30%)	3 (30%)	NS
	Mean infusion duration, hours	22 ± 8	21 ± 10	22 ± 9	NS

Results	Endpoint	Midazolam (n=10)	Dexmedetomidine 0.25 mcg/kg/hr (n=10)	Dexmedetomidine 0.5 mcg/kg/hr (n=10)	p-value
	Mean Ramsay score	3.6 ± 0.9	3.7 ± 1.1	3.5 ± 0.8	NS
	Mean PICU sedation score	2.9 ± 1.2	3.1 ± 0.9	2.9 ± 1.1	NS
	Mean tracheal suction score	3.5 ± 1.2	3.2 ± 1.4	3.5 ± 1.3	NS
	Mean BIS number	57 ± 8	51 ± 12	60 ± 10	NS
	Results below reflected for midazolam vs dexmedetomidine 0.25 mcg/kg/hr vs dexmedetomidine 0.5 mcg/kg/hr Morphine boluses administered: 36 vs 29 vs 20 Midazolam vs dexmedetomidine 0.25 mcg/kg/hr: p=NS Midazolam vs dexmedetomidine 0.5 mcg/kg/hr: p=0.02 Total morphine use (mg/kg/day): 0.74 ± 0.5 vs 0.55 ± 0.38 vs 0.28 ± 0.12 Midazolam vs dexmedetomidine 0.25 mcg/kg/hr: p=NS Midazolam vs dexmedetomidine 0.5 mcg/kg/hr: p=0.01 Dexedetomidine 0.25 mcg/kg/hr vs dexmedetomidine 0.25 mcg/kg/hr: p<0.05 Inadequate sedation (Ramsay score = 1) Midazolam vs dexmedetomidine 0.25 mcg/kg/hr: p=NS Midazolam vs dexmedetomidine 0.5 mcg/kg/hr: p=0.052
Adverse Events	No significant difference in systolic and diastolic blood pressures between groups Heart rate significantly lower in both dexmedetomidine groups than midazolam group (142 ± 36 vs 122 ± 31 vs 112 ± 26) 1 patient withdrawn from study due to bradycardia (heart rate 40-50 beats/min)
Study Author Conclusions	At a dose of 0.25 mcg/kg/hr, dexmedetomidine was approximately equivalent to midazolam at 0.22 mg/kg/hr. At 0.5 mcg/kg/hr, dexmedetomidine provided more effective sedation as demonstrated by the need for fewer boluses of morphine, a decrease in the 24-hour requirements for supplemental morphine, as well as a decrease in the total number of assessment points with a Ramsay score of 1 (inadequate sedation) and the number of patients who had a Ramsay score of 1.
Critique	Although this study used a validated sedation scale for pediatric sedation assessment and determined equivalent dosing between agents, it was limited by a small sample size and focus exclusively on PICU patients. Despite significantly less adjunctive morphine use in the high-dose dexmedetomidine 0.5 mcg/kg/hr group vs midazolam group, there was no significant difference in mean sedation scores for any of the 3 scoring tools used. Additionally, the exact means by which the equivalent dosing was calculated was not disclosed in the study.

Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial
Design	Prospective, double-blind, randomized trial N= 375
Objective	To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients
Study Groups	Dexmedetomidine (n= 244) Midazolam (n= 122)
Inclusion Criteria	Eligible patients were 18 years or older, intubated and mechanically ventilated for less than 96 hours prior to start of study drug, and had an anticipated ventilation and sedation duration of at least 3 more days
Exclusion Criteria	Trauma or burns as admitting diagnoses, dialysis of all types, pregnancy or lactation, neuromuscular blockade other than for intubation, epidural or spinal analgesia, general anesthesia 24 hours prior to or planned after the start of study drug infusion, serious central nervous system pathology, acute hepatitis or severe liver disease, unstable angina or acute myocardial infarction, left ventricular ejection fraction less than 30%, heart rate less than 50/min, second- or third-degree heart block, or systolic blood pressure less than 90 mm Hg despite continuous infusions of 2 vasopressors before the start of study drug infusion
Methods	Patients received dexmedetomidine (0.2-1.4 µg/kg per hour) or midazolam (0.02-0.1 mg/kg per hour) titrated to achieve light sedation (RASS scores between −2 and 1) from enrollment until extubation or 30 days. Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU. Optional loading doses were administered at the investigator’s discretion. Open-label midazolam and fentanyl were used as needed.
Duration	March 2005 to August 2007
Outcome Measures	Primary: Percentage of time within target RASS range Secondary: Prevalence and duration of delirium, duration of mechanical ventilation, ICU length of stay, adverse events
Baseline Characteristics		Dexmedetomidine (n= 244)	Midazolam (n= 122)
	Age, mean (SD), years	61.5 (14.8)	62.9 (16.8)
	Men	125 (51.2%)	57 (46.7%)
	APACHE II score, mean (SD)	19.1 (7.0)	18.3 (6.2)
	Medical ICU patients	212 (86.9%)	103 (84.4%)
	Surgical ICU patients	32 (13.1%)	18 (14.7%)
	Severe sepsis	182 (74.6%)	94 (77.1%)
	Delirium at enrollment (CAM-ICU–positive)	138 (60.3%)	70 (59.3%)
Results		Dexmedetomidine (n= 244)	Midazolam (n= 122)	p-value
	Time in target sedation range, mean %	77.3%	75.1%	0.18
	Prevalence of delirium	54%	76.6%	<0.001
	Time to extubation, median days (95% CI)	3.7 (3.1-4.0)	5.6 (4.6-5.9)	0.01
	ICU length of stay, median days (95% CI)	5.9 (5.7-7.0)	7.6 (6.7-8.6)	0.24
Adverse Events	Bradycardia was more common in dexmedetomidine-treated patients (42.2% vs 18.9%; P<.001), with a nonsignificant increase in the proportion requiring treatment (4.9% vs 0.8%; P=.07). Tachycardia (25.4% vs 44.3%; P<.001) and hypertension requiring treatment (18.9% vs 29.5%; P=.02) were less common in dexmedetomidine-treated patients.
Study Author Conclusions	There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia.
Critique	The study was well-designed with a large sample size and a robust methodology, including a double-blind, randomized design. However, the exclusion of patients requiring renal replacement therapy may limit the generalizability of the findings. Additionally, the study did not compare dexmedetomidine with other commonly used sedatives like lorazepam or propofol, which could provide a broader understanding of its efficacy and safety profile.

References:
[1] [1] Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489-499. doi:10.1001/jama.2009.56

Dexmedetomidine vs Midazolam for Sedation in Mechanically Ventilated Children: A Randomized Controlled Trial
Design	Open label, non-inferiority, randomized controlled trial N= 49
Objective	To compare the efficacy of dexmedetomidine and midazolam for sedation in mechanically ventilated children aged 1 month to 15 years
Study Groups	Midazolam group (n= 24) Dexmedetomidine group (n= 25)
Inclusion Criteria	Mechanically ventilated children, 1 month to 15 years old, admitted in a pediatric intensive care unit of a tertiary care referral center between August, 2016 to April, 2018
Exclusion Criteria	Children with catecholamine resistant shock, children already on sedative drug infusion, bradycardia, atrioventricular conduction block, primary central nervous system involvement at the time of admission, hepatic impairment, infusion of muscle relaxants, or previous participation in this study
Methods	Children were randomized to either dexmedetomidine or midazolam. Midazolam bolus of 0.1mg/kg and fentanyl bolus of 1 mcg/kg were given to both groups prior to initiation of infusion. Starting doses were 1 mcg/kg/min for midazolam and 0.25 mcg/kg/h for dexmedetomidine. Sedation level was assessed using Penn State Children Hospital sedation algorithm. Doses were titrated based on sedation score. Infusion continued till seven days or weaning from mechanical ventilation.
Duration	August 2016 to April 2018
Outcome Measures	Primary: Percentage of time spent in level 4 or 5 of Penn State Children Hospital (PSCH) sedation algorithm
Baseline Characteristics		Dexmedetomidine group (n=23)	Midazolam group (n=24)
	Age, months (IQR)	8 (3-24)	5.5 (2.5-11.7)
	Male	12 (52%)	12 (50%)
	% Predicted mortality (IQR)	13.5 (13.3-27)	13.5 (13-21)
	Weight, z scores	-2.52 (-3.61 to -1.59)	-3.64 (-4.76 to -2.65)
	Length, z scores	-1.84 (-2.48 to -0.62)	-1.74 (-3.31 to -0.87)
Results		Dexmedetomidine group (n=23)	Midazolam group (n=24)	p-value
	Sedation duration, hours (IQR)	26 (14-48)	53 (31-83.5)	0.014
	Time spent in level 4 or 5 of PSCH sedation algorithm, hours (IQR)	20 (6-28)	38 (20.5-66)	0.006
	Time spent in Level 4 or 5 of PSCH sedation algorithm, % (SD)	56.5 ± 28.6	67.3 ± 18.8	-
Adverse Events	Four (17.4%) children in dexmedetomidine group developed persistent bradycardia
Study Author Conclusions	Non-inferiority of dexmedetomidine compared to midazolam for sedation in children on mechanical ventilation could not be established.
Critique	The study is one of the few randomized controlled trials in mechanically ventilated children for sedation, especially in the Indian scenario. However, it has limitations such as lack of assessment of withdrawal symptoms, targeted sample size not covered, observer bias due to the study being open label, and exclusion criteria being relaxed for some children. Further studies with adequate sample size are required to ascertain the utility of dexmedetomidine as a sedative for mechanically ventilated children.

References:
[1] Gulla KM, Sankar J, Jat KR, Kabra SK, Lodha R. Dexmedetomidine vs Midazolam for Sedation in Mechanically Ventilated Children: A Randomized Controlled Trial. Indian Pediatr. 2021;58(2):117-122

Clinical Sedation Scores as Indicators of Sedative and Analgesic Drug Exposure in Intensive Care Unit Patients
Design	Prospective, observational study N= 18
Objective	To explore the relationships between clinical sedation scores, sedative/analgesic drug doses, and plasma drug concentrations in critically ill patients, the majority of whom were elderly
Study Groups	All patients (N= 18)
Inclusion Criteria	Adult, mechanically ventilated patients admitted to the medical ICUs of the 500-bed Saint Thomas Hospital between April and June 2004 who required use of fentanyl, lorazepam, or propofol
Exclusion Criteria	Dependence on mechanical ventilation for >2 weeks and a decision to withdraw care or extubate before enrollment
Methods	Sedative/analgesic medications were administered according to clinical guidelines. Patients' sedation levels were measured twice daily using the Richmond Agitation-Sedation Scale (RASS). Dosing of fentanyl, lorazepam, and propofol was recorded. Blood was sampled twice daily for up to 5 days to analyze plasma drug concentrations. The study focused on an ICU population receiving these agents for at least 48 hours but <2 weeks
Duration	April to June 2004
Outcome Measures	Primary: Correlation between clinical sedation scores and drug doses/plasma concentrations Secondary: Correlation between interval drug doses and plasma concentrations
Baseline Characteristics		All patients (n= 18)
	Age, mean (SD) years	66.1 (18.1)
	Female	11
	Male	7
	APACHE II score, mean (SD)	27.8 (7.5)
	Weight, mean (SD) kg	90.1 (40.2)
Results		Interval dose correlation with RASS	Plasma concentration correlation with RASS
	Fentanyl	-0.39 (P = 0.002)	-0.46 (P = 0.002)
	Lorazepam	-0.28 (P = 0.001)	-0.49 (P < 0.001)
	Propofol	-0.46 (P < 0.001)	-0.18 (P = 0.07)
Adverse Events	Not specifically reported in the study
Study Author Conclusions	Elderly patients are commonly encountered in the ICU setting. Only moderate correlations existed between clinical sedation levels and dose or plasma concentration of sedative/analgesic medications in this study population. Further work is needed to understand appropriate and feasible measures of exposure to sedatives/analgesics relating to clinical outcomes
Critique	The study provided valuable insights into the relationship between sedation scores and drug exposure in critically ill elderly patients. However, the small sample size and observational design limit the generalizability of the findings. The study did not assess the impact of sedation scores and drug exposure on clinical outcomes such as mortality or cognitive function. Additionally, the lack of AUC measurements and potential confounding factors such as comorbidities and drug interactions were not fully addressed

References:
[1] Masica AL, Girard TD, Wilkinson GR, et al. Clinical sedation scores as indicators of sedative and analgesic drug exposure in intensive care unit patients. Am J Geriatr Pharmacother. 2007;5(3):218-231. doi:10.1016/j.amjopharm.2007.10.005