Assessing and Managing Sedation in the Intensive Care and the

Perioperative Settings

SEDATION Curriculum Learning Objectives

• Manage adult patients who need sedation and analgesia while receiving ventilator support according to current standards and guidelines

• Use validated scales for sedation, pain, agitation, and delirium in the management of these critically ill patients

• Assess recent clinical findings in sedation and analgesia management and incorporate them into the management of patients in the acute care, procedural, and surgical sedation settings

Procedural SedationMajor Applications

• Surgical– Neurosurgery

– Bariatric surgery

– Oral

– Plastic/reconstructive

– Biopsy

– CV surgery

• Endoscopic– Bronchoscopy

– Fiberoptic intubation

– Colonoscopy

Growth of Ambulatory Surgery Centers (ASC)

• ASCs increased outpatient operations from

< 10% in 1979 to 50% in 19901 • From 1993 to 20012

– ASCs in metropolitan areas increased by 150%– Hospital outpatient surgeries increased 28%– Inpatient surgeries decreased by 4.5%

• 70% of surgical interventions in the United States are outpatient procedures1

1. Pregler JL, et al. Anesthesiol Clin North America. 2003;21(2):207-228. 2. Bian J, et al. Inquiry. 2009-2010;46(4):433-447.

Common Agents for Conscious Sedation

Mustoe TA, et al. Plast Reconstr Surg. 2010;126(4):165e-176e.

Factors Jeopardizing Safety

• Risk of major blood loss• Extended duration of surgery (> 6 h)• Critically ill patients (evaluate and document prior to

procedure) • Need for specialized expertise or equipment (cardio-

pulmonary bypass, thoracic or intracranial surgery)• Supply and support functions or resources are limited• Inadequate postprocedural care• Physical plant is inappropriate or fails to meet

regulatory standards

Eichhorn V, et al. Curr Opin Anaesthesiol. 2010;23(4):494-499.

Standardized Monitoring• Hemodynamic

– ECG– Blood pressure

• Respiration– Oxygenation (SpO2 by pulse oximetry, supplemental oxygen)

– Ventilation (end tidal CO2, EtCO2)

• Temperature (risk of hypothermia)• Higher risk at remote locations

– Inadequate oxygenation/ventilation– Oversedation– Inadequate monitoring

Eichhorn V, et al. Curr Opin Anaesthesiol. 2010;23(4):494-499.

Endoscopic Procedures

Sedation for Endoscopy

• Desirable qualities– Permits complete

diagnostic exam– Safe – Diminishes memory of

the procedure– Permits rapid discharge

after procedure

• Risk factors– Depth of sedation– ASA status– Medical conditions– Pregnancy – Difficult airway mgt– Extreme age– Rapid discharge time

Runza M. Minerva Anestesiol. 2009;75:673-674.

Drugs for Fiberoptic Intubation

Agent Class

Example Advantages Considerations

GABA agonist

Benzodiazepine Midazolam

•Quick onset• Injection not painful•Short duration

• Not analgesic• Airway reflexes persist

GABA agonist

Benzodiazepine Propofol

•Quick onset • Respiratory depression• Unconsciousness• Decreased bp, cardiac

output• Increased HR

Opioid FentanylRemifentanil

•Analgesic•Cough suppressive

• Respiratory depression

a2 Agonist Dexmedetomidine •Pt easily arousable•Anxiolytic •Analgesic•No respir. depression

• Transient hypertension• Hypotension • Bradycardia

Summary courtesy of Pratik Pandharipande, MD.

Propofol vs Combined Sedationin Flexible Bronchoscopy

• Randomized non-inferiority trial• 200 diverse patients received propofol or

midazolam/hydrocodone• 1o endpoints

– Mean lowest SaO2

– Readiness for discharge at 1h

• Result– No difference in mean lowest SaO2

– Propofol group had Higher readiness for discharge score (P = 0.035)

Less tachycardia

Higher cough scores

• Conclusion: Propofol is a viable alternative to midazolam/hydrocodone for FB

Stolz D, et al. Eur Respir J. 2009;34:1024-1030.

Dexmedetomidine vs Midazolam for Upper Endoscopy

50 adults undergoing upper endoscopy

Dexmedetomidine• Bolus 1 µg/kg • Infusion 0.2 µg/kg/hr

( n = 25)

Midazolam 0.07 mg/kg • Total dose 5 mg

(n = 25)

Demiraran Y, et al. Can J Gastroenterol. 2007;21(1):25-29.

Upper Endoscopy Results

• Dexmedetomidine was similar to midazolam – Gagging– Patient satisfaction– Patient discomfort– Anxiety scores– Recovery time

• Dex was superior to midazolam– Endoscopist satisfaction– Retching – Total number of patients having

any type of side effects

VariableMidazolam

(n = 25)Dex

(n = 25)P-value

Time to full recovery, min

37.6±11 42±12.5 0.30

Patients fully recovered, n (%)

15 min 12 (48) 10 (40) 0.56

30 min 20 (80) 18 (72) 0.74

45 min 25 (100) 25 (100) 0.99

Demiraran Y, et al. Can J Gastroenterol. 2007;21(1):25-29.

Recovery

Dexmedetomidine Increases Comfort in AFOI • Double-blinded randomized trial• Midazolam +/- dexmedetomidine• Awake fiberoptic intubation (AFOI)• Patient comfort rated by 2 observers

Bergese SD, et al. J Clin Anesth. 2010;22(1):35-40.

Tota

l C

om

fort

Sco

re (

max

= 3

5)

Pre-oxygenation

Introduction of scope

Introduction of ET tube

n = 24n = 31

Use of Sedation for Colonoscopy

Austra

lia

Hong

Kong

Unite

d Sta

tes

Germ

any

Switzer

land

Greec

e Ita

ly

China

0

10

20

30

40

50

60

70

80

90

100

Cohen LB. Gastrointest Endosc Clin N Am. 2010;20(4):615-627.

Co

lon

osc

op

ies

Wit

h S

edat

ion

(%

)

Sedative Use for Colonoscopy: USA

74%

18%

8%

Cohen LB, et al. Am J Gastroenterol. 2006;101(5):967-974.

BZD + Opioid

BZD + Opioidand/or

Propofol

Propofol

BZD + Opioid

37%

1%

Endoscopist Choices for Their Own Colonoscopy

41%

14%

8%

Cohen LB, et al. Am J Gastroenterol. 2006;101(5):967-974.

* More than one answer was permitted

Propofol

No Sedation

BZD AloneOpiod Alone

Outpatient Colonoscopy: Study Design

90 colonoscopy patients

Dex 1 µg/kg over 15

mins, then 0.2 µg/kg/hr (n = 19)

Meperidine 1 mg/kg with

midazolam 0.05 mg/kg (n = 21)

Fentanyl 0.1-0.2 mg on

demand (n = 24)

Jalowiecki P, et al. Anesthesiology. 2005;103(2):269-273.

• Study halted after 64 subjects because of AE in the Dex group• Hb saturation and respiration rate variations not observed

Outpatient Colonoscopy: Results

Jalowiecki P, et al. Anesthesiology. 2005;103(2):269-273.

Dex (n = 19)

Meperidine (n = 21)

Fentanyl(n = 24)

Average MAP reduction 26% 14% 3%

Maximum BP reduction50%

(4 cases)35% 30%

Mean HR reduction 17% 9% 7%

Lowest HR 40 bpm (2 cases) 50 bpm 50 bpm

Vertigo & nausea (n) 5 0 0

Time to discharge readiness (min) 85 39 32

Jaw thrust maneuver 0 6 (29%) 0

Jalowiecki P, et al. Anesthesiology. 2005;103(2):269-273.

Outpatient Colonoscopy: Hemodynamics

* P < 0.05 after Bonferroni correction

Elective Colonoscopy: Can the Patient Control Sedation?

• Patient-controlled sedation (PCS) with propofol-remifentanil (PR) – Rapid sedation

– Rapid recovery

– More airway rescue needed with PR than with MDZ-fentanyl

• Prospective, randomized, open-label trial– n = 25 Patient-controlled sedation (PCS)

– n = 25 Anesthesiologist-administered sedation (AAS)

• Procedure – Outpatient colonoscopy

– All patients received propofol-remifentanil

– 100% oxygen via an anesthesia mask

– Continuous spirometry and bispectral index (BIS) monitoring

• Primary endpoint: oversedation– Respiratory rate

– BIS

Mandel JE, et al. Gastrointest Endosc. 2010;72(1):112-117.

Outpatient Colonoscopy: Respiratory Depression

Mandel JE, et al. Gastrointest Endosc. 2010;72(1):112-117.

Respiratory Rate (breaths/min)

Rel

ativ

e F

req

uen

cy

• AAS group used more mean total drug

• Safety interventions

– Criterion: 30s of SaO2 < 90%

– PCS: 0/25

– AAS: 5/25

• Median BIS values– PCS: 88.1

– AAS: 71.7 P < 0.001

Bariatric Surgery

Propofol or BZD/Narcotics forPre-Surgical Endoscopy?

• Endoscopy prior to bariatric surgery• Anesthesiologist-monitored sedation

(AMS)– IV propofol (n = 51)

• Surgeon-monitored sedation (SMS)– IV narcotics and benzodiazepines

• Study design – Observational study

– Data from patient survey

– Doses/regimens not reported

• Results– Generally no difference between methods

– Trend toward amnesia in AMS group

Patient YES responses (%)

Throat pain during procedure

Throat pain after procedure

Remembered scope placement

Remembered gagging

Reported recovery < 1 hour

Nausea after endoscopy

0 10 20 30 40 50 60

AMS

SMS

P < 0.02

Madan AK, et al. Obes Surg. 2008;18(5):545-548.

Fentanyl vs Dexmedetomidine Use in Bariatric Surgery

• 20 morbidly obese patients• Roux-en-Y gastric bypass surgery• All received midazolam, desflurane to maintain BIS at

45–50, and intraoperative analgesics– Fentanyl (n = 10) 0.5 µg/kg bolus, 0.5 µg/kg/h– Dexmedetomidine (n = 10) 0.5 µg/kg bolus, 0.4 µg/kg/h

• Dexmedetomidine associated with – Lower desflurane requirement for BIS maintenance– Decreased surgical BP and HR – Lower postoperative pain and morphine use (up to 2 h)

Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.

• 80 morbidly obese patients• Gastric banding or bypass surgery• Prospective dose ranging study• Medication

– Celecoxib 400 mg po

– Midazolam 20 µg/kg IV– Propofol 1.25 mg/kg IV– Desflurane 4% inspired– Dexmedetomidine 0, 0.2, 0.4, 0.8 µg/kg/h IV

Dexmedetomidine as Desflurane Adjuvant in Bariatric Surgery

Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.

• More dex 0.8 patients required rescue phenylephrine for hypotension than control pts (50% vs 20%, P < 0.05)

• All dex groups – Required less desflurane (19%–22%)– Had lower MAP for 45’ post-op– Required less fentanyl after awakening (36%–42%)– Had less emetic symptoms post-op

• No clinical difference – Emergence from anesthesia– Post-op self-administered morphine and pain scores – Length of stay in post-anesthesia care unit– Length of stay in hospital

Dexmedetomidine as Desflurane Adjuvant in Bariatric Surgery: Results

Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.

Oral Surgery

EndodontistsN = 31

Sublingual Triazolam/Halcion (45.2%)Oral Triazolam/Halcion( 19.5%)No Premedication Agents Used (19.4%)

MD AnesthesiologistsN = 19

All Agents Identified Are Used (52.6%)Intramuscular Ketamine (26.3%)Oral Midazolam (10.5%)

Dental AnesthesiologistsN = 75

All Agents Identified Are Used (32.0%)Intramuscular Ketamine (22.4%)Intramuscular Ketamine & Midazolam (14.7%)

General DentistsN = 144

Oral Triazolam/Halcion (45.1%)No Premedication Agents Used (25.7%)Sublingual Triazolam/Halcion (13.9%)

PeriodontistsN = 55

Oral Triazolam/Halcion (38.2%)No Premedication Agents Used (32.7%)Sublingual Triazolam (14.5%)

Pediatric DentistsN = 33

Demerol and Hydroxyzine Elixir (36.4%)Oral Midazolam (27.2%)No Premedication Agents Used (21.2%)

Oral/Maxillofacial SurgeonsN = 356

No Premedication Agents Used (54.2%)Oral Midazolam (9.6%)Oral Triazolam/Halcion (8.1%)

Public Health PractitionerN = 2

Oral Triazolam/Halcion (50.0%)No Premedication Agents Used (50.0%)

ProsthodontistsN = 2

Oral Triazolam/Halcion (100%)

Dental Anesthesia Survey:Premedication by Specialty

Boynes SG, et al. Anesth Prog. 2010;57(2):52-58.

Dental Anesthesia Survey:Sedation/Anesthesia Method by Specialty

Boynes SG, et al. Anesth Prog. 2010;57(2):52-58.

OMFSN = 356

Per

cen

t

DENT ANESN = 75

PED DENT N = 33

PERIO N= 55

OMD ANESN N = 19

GEN DENT N = 144

ENO N = 31

Oral SedationIV Conscious SedationIV Deep SedationGETA

Plastic/Reconstructive Surgery

Cosmetic Procedures

• In 2007, 11.7 million procedures in US– Liposuction– Breast augmentation– Eyelid surgery– Abdominoplasty– Breast reduction

• Site– Surgeons’ offices 54%– Ambulatory centers 29%– Hospitals 17%

Shapiro FE. Curr Opin Anaesthesiol. 2008;21(6):704-710.

Face Lift Surgery

• Retrospective study– Single surgeon– Multiple anesthetists

• Groups– N = 77 Standard of care (mainly propofol,

ketamine, fentanyl, and midazolam)– N = 78 SOC plus dexmedetomidine– Not randomized, treated per anesthetist choice– All patients in deep sedation

Taghinia AH, et al. Plast Reconstr Surg. 2008;121(1):269-276.

Face Lift Surgery:Hemodynamic Results

Taghinia AH, et al. Plast Reconstr Surg. 2008;121(1):269-276.

SOC+ Dex SOC

Laparoscopy

Ambulatory Gynecologic Laparoscopy

ASA I-II patients • N = 60• Prospective• Randomized • Double blind

Remifentanil• 1 µg/kg over 10 mins then• 0.2 µg/kg/min

Dex • 1 µg/kg over 10 mins then• 0.4 µg/kg/hr

Salman N, et al. Saudi Med J. 2009;30(1):77-81.

Dexmedetomidine associated with• Slower recovery

• Less nausea and vomiting

• Lower analgesia requirement

Recovery Data Group Remifentanil Group DEX

Time to eye opening (mins)

3.5 ±1.1 4.1 ±1.4

Extubation time (mins)

6.1 ±1.6 * 7.3 ±1.3

Orientation to person (mins)

9.1 ±2.3 * 10.5 ±1.8

Orientation to place and time

(mins)

16.1 ±6.3 * 21.2 ±11.7

Discharge time (mins)

200.3 ±29.5 224.5 ±49.2

*P < 0.05

Salman N, et al. Saudi Med J. 2009;30(1):77-81.

Ambulatory Gynecologic Laparoscopy

CV Surgery

What Do Neurointerventionalists Prefer for AIS Interventions?

*Treated as ordinal

4 = Most frequent

3 = Frequent

2 = Least frequent

1 = Never

McDonagh DL, et al. Front Neurol. 2010;1:118.

General Anesthesia During AIS Intervention?

McDonagh DL, et al. Front Neurol. 2010;1:118.

Trial of Dexmedetomidine for CV Procedure: Design

• Prospective, randomized, double-blinded, placebo-controlled multicenter trial

• Procedure – AV fistula creation and peripheral vascular stent placement– Local anesthesia or peripheral nerve block

• Patients randomized 2:2:1 – Dex 1.0 mg/kg load, then infusion of 0.6 mg/kg/h– Dex 0.5 mg/kg load, then infusion of 0.6 mg/kg/h– Normal saline 0.9% infusion

• Drug titrated to achieve a target OAA/S of ≤ 4• Fentanyl in 25 μg increments IV for pain• 1o EP: % patients not requiring MDZ during infusions

Huncke TK, et al. Vasc Endovascular Surg. 2010;44(4):257-261.

Trial of Dexmedetomidine for CV Procedure: Results

Number (%) of Patients Not Requiring Rescue Midazolam (MDZ)

The Perioperative Use of MDZ and Fentanyl

Huncke TK, et al. Vasc Endovascular Surg. 2010;44(4):257-261.

Sedation/Analgesia for Traumatic Brain Injury

Goal: reduce ICP by decreasing pain, agitation

Saiki RL. Crit Care Nurs Clin North Am. 2009;21:549-559.

Agent Advantages Considerations

Propofol

• Short acting• Reduces cerebral

metabolism, O2 consumption

• Improves ICP after 3d

• Propofol infusion syndrome

Barbiturates• Reduce ICP• Neuroprotection

• Interfere with neuro exam• Hypotension, reduced CBF• OCs not improved with severe TBI

44

• Randomized, double-blind, placebo-controlled, multicenter

• 326 pts undergoing MAC for surgery (orthopedic, ophthalmic, vascular, excision of lesions, others < 10%)

• All patients sedated – Observer’s Assessment of Alertness/Sedation Scale (OAA/S ) to < 4

• Sedation with – Dex ± rescue midazolam, or

– Placebo + rescue midazolam

• Fentanyl PRN for pain

MAC with Dexmedetomidine

Candiotti KA, et al; MAC Study Group. Anesth Analg. 2010;110(1):47-56.

MAC = Monitored anesthesia care

Placebo Dex 0.5 Dex 1.00

25

50

75

100 96.8

59.7

45.7

Mid

azo

lam

Tre

atm

ent,

%

Placebo Dex 0.5 Dex 1.00

1

2

3

4

5

4.1

1.40.9

Mid

azo

lam

, m

g

**

144.4

84.8 83.6

0

50

100

150

200

Placebo Dex 0.5 Dex 1.0

Fe

nta

ny

l, µ

g Midazolam UseFentanyl Use

Dexmedetomidine Reduces Fentanyl and Midazolam Use During MAC

*P < 0.001 compared with placebo, MAC = monitored anesthesia care

**

Placebo Dex 0.5 Dex 1.00

25

50

75

10088.9

59.0

42.6

Fen

tan

yl T

reat

men

t, %

*

*

*

*

Candiotti KA, et al; MAC Study Group. Anesth Analg. 2010;110(1):47-56.