Dr. Surendra FNB-CCMRTIICS KOLKATA

Hypnosis

± MuscleRelaxation

Analgesia

•Latin word sedare = to calm or to allay fear = sedation

Conscious sedation•A minimally depressed level of

consciousness induced by the administration of pharmacologic agents in which a patient retains the ability to independently and continuously maintain an open airway and a regular breathing pattern, and to respond appropriately and rationally to physical stimulation and verbal commands

THE PATIENT IS HERE!

Chest 2008;133;552-565

Complications from pain and anxietyStimulation of the autonomic nervous

system and release of humoral factors → increased HR, BP, and myocardial oxygen consumption → myocardial ischemia or infarction

Altered humoral response can lead to

hypercoagulability as a result of increased level of factor VIII, fibrinogen, platelet activity, and inhibition of fibrinolysis

Cont……..Stress hormones also produce insulin

resistance, increased metabolic rate, and protein catabolism

Immunosuppression with reduction in number and function of lymphocytes and granulocytes

Psychological disturbances - memories of vivid nightmares, hallucinations, and paranoid delusions

DeliriumDelirium80% of ICU patients have delirium

*may or may not be accompanied by agitation

Indications and Goals

Facilitate mechanical ventilationCreate anxiolysis, analgesia,

amnesiaDecrease oxygen consumptionReduce dyspneaPrevent patient self-injury“Rest” patient for weaning trialsInduce sleep

Cont……Create patient unawareness Improve long-term

psychiatric outcomes (?)Permit delivery of efficient

careReduce nursing stressEnsure nursing safetyIncrease family acceptance

of ICU careWeinert, et al. AJCC. 2001; 10:156

Sedation EvaluationSedation EvaluationShould be integral component of treatment algorithmsprecise dosingreduced sedative and analgesic drug use shorter duration of MVreduced need for vasopressor therapyreduced incidence of over sedation

Guidelines---SCCM-2013

scoring system

should be simple, easily performed, noninvasive, and

reproducible.

Richmond Agitation-Sedation Scale (RASS)Sedation Agitation Scale [SAS]Motor Activity Assessment ScaleRamsay Sedation ScaleAdaptation to the Intensive Care Environment

(ATICE) instrumentMinnesota Sedation Assessment Tool (MSAT). Glasgow coma scale (GCS) – assessment of level of

consciousness

Richmond agitation sedation scaleScore Term Description

+4 Combative Violent; immediate danger to staff

+3 Very agitated Pulls/ removes tubes, catheters; aggressive

+2 Agitated Frequent non purposeful movement; patient ventilator asynchrony

+1 Restless Anxious or apprehensive

0 Alert and calm

-1 Drowsy Not fully alert but awakens for >10s, with eye contact, to voice

-2 Light sedation Briefly awakens (<10s), with eye contact, to voice

-3 Moderate sedation

Any movement to voice but no eye contact

-4 Deep sedation No response to voice but movement to physical stimulation

-5 Unarousable No response to voice or physical stimulation

Ramsay sedation scaleAwake1 Anxious and/or agitated2 Cooperative, oriented, and tranquil3 Responds to commandsAsleep4 brisk response to light glabellar

tap or loud auditory stimulus5 Sluggish response to light glabellar

tap or loud auditory stimulus6 No response

Sedation agitation scale1: Unarousable 2: Very sedated 3: Sedated 4: Calm and cooperative 5: Agitated 6: Very agitated 7: Dangerous agitation

What is “adequate sedation”?RAAS -0-3SAS – 3-4RAMSAY- 3

Measurement of Brain ActivityMeasurement of Brain ActivityBispectral index (BIS)Patient state indexCerebral state indexNarcotrend index

•Objective physiologic Objective physiologic parametersparameters

•Numerical displayNumerical display•Near-continuous measurementNear-continuous measurement

Bispectral indexA practical, processed EEG

parameter that measures the direct effects of sedatives on the brain

.

BIS range guidelines

Value of BIS in ICU

Minimize consequencesof over- and

under-sedation

Improve quality of sedation management

Objective sedation assessmentabout a patient’s response to sedation

Optimize clinical and economic

outcomes

Numerical scale correlates to sedation endpoints

BISProne to artifacts‘Electromyography‘ activity interferes with BIS

measures of sedationConfounding factors that may influence BIS scores

Hypoglycemia / Sleep / temperature / AgeDrugs

aminophylline, epinephrine, and ketamine.Increase variability of BIS in the critically ill ptsCannot be relied upon in circulatory arrest or

hypothermia

Daily interruption of sedation & analgesia [1B]Allows better assessment of a patient’s

sedative needsReduces drug bioaccumulationReduced incidence of posttraumatic stress

disorderReduced complications of critical illnessMore ventilator-free days and earlier ICU and

hospital discharge, at the expense of a higher incidence of self-extubation

Sedation therapyNON PHARMACOLOGICAL THERAPY:Good communication with regular

reassurance from nursing staffEnvironmental control such as

humidity, lighting, temperature, and noiseExplanation prior to proceduresManagement of thirst, hunger,

constipation, and full bladder

Critically ill patients are differentPharmacokinetics of various drugs are

altered including - drug bioavailability, volume of distribution, and clearance.Hepatic dysfunctionDecreased hepatic blood flowRenal dysfunctionAlteration in volume statusPlasma protein binding

Pharmacologic therapyThe sedative agent should possess the

following qualities:Both sedative and analgesic propertiesMinimal cardiovascular side effectsControllable respiratory side effectsRapid onset/offset of actionNo accumulation in renal/hepatic

dysfunctionInactive metabolitesInexpensiveNo interactions with other ICU drugs

Pharmacologic therapy

BenzodiazepinesPropofolEtomidateKetamineBarbiturate Short acting opioidsAlpha 2 agonistsInhalational agents

Benzodiazepines Anxiolytic, anticonvulsant, amnesic,

hypnotic and provide some muscle relaxation

Effects are mediated by depressing the excitability of the limbic system via reversible binding at GABA-benzodiazepine receptor complex

Minimal cardiorespiratory depressant effectThe common drugs in this class are

diazepam, midazolam, and lorazepam

Pharmacodynamic response Patient-related factors can affect the

BZD responseageconcurrent pathologyprior alcohol useconcurrent therapy with other sedative drugs

Higher volume of distribution and slower clearance in elderly.

MIDAZOLM LORAZEPAM DIAZEPAM

LOADING DOSE 0.01-0.05 mg/kg 0.02-0.04 mg/kg 0.05-0.2 mg/kg

MAINTANENCE DOSE

0.02-0.1 mg/kg/hr

0.01-0.1 mg/kg/hr

Rarely used

ONSET 1-5 min 5-20 min 2-5 min

DURATION 3-11 hrs 2-6 hrs 2-4 hrs

CARDIAC EFFECTS

Minimal Minimal Present

RESPIRATORY EFFECTS

Important depressant effect

Important depressant effect

Important depressant effect

ANALGESIA None None None

AMNESIA Potent None None

ACTIVE METABOLITES

Yes No Yes

S/E Low BP Low BP, glycol/nephrtoxicity

Low BP, pleibitis

Propofol The mode of action of propofol is via the GABA

receptorRapid onset of action 1-2 min; metabolized rapidly hepatically and

extrahepatically Recovery within 10 minutes of discontinuation,

can accumulate with prolonged use Ideally infused via a large or central veinProlonged infusions –increase triglyceride and

cholesterol levels A theoretical maximum recommended dose is 4

mg/kg/hour.

Propofol (contd.)Bolus dose – not recommendedInfusions @25 to 100μg/kg/hrTheoretical maximum dose- 4mg/kg/hrCautious about propofol infusion syndrome

Propofol: adverse effectsHypotension

Reliable, dose-related Decreased SVR and contractility (CO)

Respiratory depression Apnea with bolus dosing

Synergistic CV and respiratory depression with opioids

Vehicle (soybean emulsion): Hypertriglyceridemia Venoirritation Infection

Propofol infusion syndromePropofol infusion syndrome is an adverse

drug event associated with high doses (>4 mg/kg per hour or >67 µg/kg per minute) and long-term (>48 hours) use of propofol.

Clinical features:- Cardiomyopathy with acute cardiac failure.- Myopathy.- Metabolic acidosis, K+ - Hepatomegaly.

Inhibition of FFA entry into mitochondria failure of its metabolism.

Management Supportive treatments addressing the clinical

manifestations The propofol infusion should be discontinued

immediately Alternative sedative should be started Intravenous crystalloid and colloid replacement

and vasopressor and/or inotropic support Cardiac pacing may be used for symptomatic

bradycardia Hemodialysis or continuous renal replacement

therapy to treat the acute renal failure

KetamineKetamine acts at the N-methyl-D-aspartate

(NMDA) receptorIn subanesthetic doses, sedative and analgesicGenerally not used because of the increase in

blood pressure, intracranial pressure (ICP), and pulse rate

Bronchodilatory properties, sometimes has a role in severe asthma

In the ICU conjunction with a narcoticDose : 5 to 30 μg/kg/min

Others ETOMIDATE :For maintenance of hypnosis, target

concentration of 300 to 500 ng/mL may be achieved by administration of a two- or three-stage infusion

BARBITURATES: Barbiturates such as Pentothal have been used in the ICU, especially in the management of patients with head injuries and seizure disorders. They cause significant cardiovascular depression and accumulate during infusions, leading to prolonged recovery times.

Others (contd.) BUTYROPHENONES AND PHENOTHIAZINESAn aggressive dosing regimen of haloperidol may

be useful in a patient with delirium to promote calm, 2 to 10 mg IV every 10 to 15 minutes until the desired response is achieved

VOLATILE AGENTSIsoflurane has been used in concentrations of up

to 0.6% for longterm sedation, with minimal cardiorespiratory side effects and rapid awakening.

Desflurane has been shown to be effective in sedation, with rapid offset of effects.

Others (contd.)Shorter acting opioidsFentanyl, alfentanyl, remifentanyl

α2 agonistsClonidinedexmedetomidine

Muscle relaxants

Fentanyl

50-100μg

1-2 min

30-60 min

50-350μg/hr

No

No

Loading dose

Onset

Duration

Infusion rate

Active metabolites

Histamine release

2 AgonistsClonidine

Selectivity: 2:1 250:1

Imidazole derivate 16:1

t1/2 10 hrsAntihypertensive

Dexmedetomidine

Selectivity: 2:1 1620:1

Imidazole derivate 31:1t1/2 2 hrs94% protein boundEliminated by

liver/kidneySedativeOnly available in IV form

Dexmed.Dexmed. Clinical paradigms

Sedation without

respiratory

deppression

Sympatholyti

csmooth emergence + weaning from mechanical ventilation

Molecular targets + neural substrates1.locus ceruleus2.natural sleep pathways

Pharmacokinetics Rapid redistribution: 6 minNo accumulation after infusions 12-24 hTypical doses (target plasma levels 0.3-1.2

ng/ml):Onset 5-10 minEt1/2 1.8-3.1 hr1 ug/kg loading dose over 10 min f/b 0.2-0.7

ug/kg/hr infusionLoad only - short proceduresPatients with high sympathetic activity may

need very high doses

Clonidine Clonidine is synergistic with opioids and

acts at the spinal cord to inhibit nociceptive inputs, thus imparting analgesia

It is contraindicated in hypovolemia and can cause hypotension, bradycardia, and dry mouth

The Art of Sedation Under sedation:Fighting the ventilator.V/Q mismatch.Accidental extubation.Catheter

displacement.CV stress ischemia.Anxiety, awareness.Post-traumatic stress

disorder.

Over sedation:Tolerance,

tachyphylaxis.Withdrawal

syndrome.Delirium.Prolonged ventilation.CV depression. neuro testing.Sleep disturbance.

Titration of Sedative Medications

Large variation in dose requirementsAltered PK/PD in critically ill Acute and chronic toleranceDifferences in severity of symptom or behavior

Most drugs are titrated to effectSimilar to hypertensive medications

How to titrate sedative medications

Identify the target symptom or behavior“Measure” the intensity or severityAgree on the appropriate symptom level for

that patient at that timeRealize that changes will occur

Propofol

Hypertriglyceridemia

CVS depression

Hypotension

2-agonists

Hypotension

Bradycardia

Benzodiazepines

Hypotension

Respiratory depression

Agitation/ConfusionKetamine

Hypertension

Secretions

Dysphoria

GeneralOver sedation

Delayed awakening/extubation

Respiratorydepression

ConfusionVasodilation

Gut motilitydepression

Opioids

WEANING FROM SEDATION

Hooper. Critical Care Clinics - 25 (July 2009)

Before Assesing daily awakening exclude

Raised ICTNMBVery high PEEP n FiO2CABG- immediate postop

Results: ABC TrialSAT + SBT = more Ventilator-free days

15 v 12 (p =0.02)Less days in ICU: 9 v 13Less coma but more self-extubationsDecreased risk of dying up to 1 yr

Girard Lancet 371:126 2008