SEDATION AND

ANALGESIA IN THE

PICU Anand Bhutada

Pediatric Intensivist, Child Hospital, Nagpur

Outlines

Introduction

Goals

Definitions

The challenges of PICU sedation

Sedation & Analgesia monitoring

Medications options

Suggested strategies

Precautions

Conclusion & key points

GOALS

Patient comfort

Control of pain

Anxiolysis

Amnesia

Blunting adverse autonomic and hemodynamic responses

Facilitate nursing management

Facilitate mechanical ventilation

Avoid self-extubation or self injury

Reduce oxygen consumption

SEDATION and ANALGESIA

Inadequate analgesia and postsurgical stress response is a metabolic, humoral, and hemodynamic response following injury or surgery

This neuroendocrine cascade leads to increased oxygen consumption, increased carbon dioxide production, and a generalized catabolic state with a negative nitrogen balance

SEDATION/ANALGESIA

Sedation (seda/shun) [L. sedatio, to calm, allay].

The act of calming, especially by the

administration of a sedative, or the state of being

calm.

Analgesia (an-al-je/zi-ah) [G. insensibility, from an -

privative,negative + algesis, sensation of pain] A

condition in which nocioceptive stimuli are

perceived but are not interpreted as pain; usually

accompanied by sedation without loss of

consciousness.

IDEAL PICU

SEDATIVE/ANALGESIA

Rapid onset

Predictable duration

No active metabolites

Rapid recovery

Multiple routes of delivery

Easy to titrate

Minimal cardiopulmonary effects

Not altered by renal or hepatic disease

No drug interactions

Antidote available

Wide therapeutic index

COMMON DRUGS UTILIZED

Opiates (Narcotics)

Benzodiazepines

Chloral hydrate

Barbiturates

Ketamine

Propofol

Neuroleptics

Paralytics

SITUATIONS REQUIRING

SEDATIVES/ANALGESIA

MECHANICAL VENTILATION

Respiratory failure

Airway

Neurological

POST OPERATIVE

HEAD INJURY

PULMONARY HYPERTENSION

PROCEDURES

FLACC (0-8 YR)

COMFORT SCALE SCORE Intubated, Non paralysed patients (Target 17- 26)

OPIOIDS

First line drugs

Provide analgesia and sedation, NOT amnesia

Act similarly as a class

Produce delayed gastric emptying, decreased intestinal peristalsis, and urinary retention

Narcotic to be used:

Morphine

Fentanyl

Methadone

OPIOIDS

ROUTE OF ADMINISTRATION IV

Oral

Transmucosal

Transdermal

MODE OF ADMINISTRATION Intermittent/on demand (as necessary)

Fixed interval

Continuous infusion

PCA

MORPHINE

Gold standard

Hepatic metabolism

Depresses respiration by altering chemoreceptor sensitivity to CO2

Depresses rate over tidal volume

Decreases sigh frequency

Can cause hypotension due to histamine mediated vasodilation

Can block compensatory catecholamine effect

Prolonged clearance in neonates

MORPHINE

IV intermittent

0.1 mg/kg q 3 - 4

hrs

IV continuous

0.05 mg - 0.1

mg/kg/hr

PO scheduled

0.3 mg/kg q 3 - 4

hrs

PCA dosing

Initial dosing: 50 mcg/kg q 10 minutes until comfortable

Demand dose: 20 - 40 mcg/kg

Lock-out period: 10 minutes

4-hour limit: 0.25 mg/kg

FENTANYL

Synthetic opiate, 100 x more potent than

morphine

Rapid onset, highly lipophilic, rapidly crosses

BBB, redistributed to fatty tissue

Short distribution t1/2, long elimination t1/2

Minimal hemodynamic effect

Blunts pulmonary vascular responses

May produce “chest wall rigidity”, reversed with

relaxants or naloxone

FENTANYL

IV intermittent dosing

1-2 mcg/kg q 1-2 hrs

IV continuous dosing

1-2 mcg/kg/hr

Transdermal delivery system available

Not recommended in children less than 12 yrs

25,50,75,100 mcg/hr

25 mcg/hr is equivalent to 15 mg morphine in a 24 hr period

METHADONE

Equipotent to morphine

Minimal hemodynamic effects

Long half life

Sedation and euphoric properties less pronounced than morphine

Useful for pain control and abstinence PO dosing

0.1 mg/kg q 4-8 hrs

50 % oral bioavailability

Drug accumulation with repeated doses caused by extensive protein binding

MODE OF ADMINISTRATION

Intravenous bolus administration

Common

PRN - as needed

Half-life of drug determines interval

Disadvantage of pain breakthrough

IV BOLUS ADMINISTRATION

CONTINUOUS INFUSION

Utilized when prolonged analgesia and

sedation needed

Less labor intensive

Better analgesia, initial bolus important

Need for dedicated IV site

CONTINUOUS INFUSION

PCA

Patient controlled analgesia

Allows patient to administer a preset amount of

narcotic at preselected intervals

Improved analgesia with decreased narcotic use

Option to include low basal rate

Nurse controlled analgesia

Eliminates delay

Allows delivery via a closed system

PCA

OPIATE SIDE EFFECTS

RESPIRATORY DEPRESSION

Reversal - Nalaxone (Narcan)

Full reversal 0.1 mg/kg

Partial reversal - titrate to effect

Half life is less than narcotics

IV,IM,Sub Q, ETT

Abrupt reversal may result in nausea,

vomiting, sweating, tachycardia, increased

BP, and tremors

OPIATE SIDE EFFECTS

Pruritis

Individual variability and susceptibility, alleviated by Benadryl

Tolerance

Need for increase in dose to achieve the same effect

Generally develops after 2-3 days of frequent/continuous use

Greater with fentanyl

Treated by increasing the dose as needed

OPIATE SIDE EFFECTS

DEPENDENCE

Physiological state leading to abstinence

syndrome on withdrawal of the drug

Generally develops after 7-10 days of

sustained use

Symptoms include: mydriasis, tachycardia,

goose bumps, muscle jerks, vomiting, diarrhea,

seizures, fever, hypertension

Treated with gradual withdrawal of the drug

OPIATE SIDE EFFECTS

DEPENDENCE

In general the longer the period of treatment the longer the period of withdrawal needed

A child is at risk for dependence if they have been on narcotics for a week

Finnegan scoring to monitor adequate weaning dose

Weaning strategies can vary, typically 10% decrease per day

Do not spread the dosing interval beyond the normal dosing interval, rather decrease the dose

Can substitute methadone and wean q 48 hrs over a longer time period

BENZODIAZEPINES

First line agents for sedation

Provide hypnosis, anxiolysis, antegrade amnesia, and anticonvulsant activity

NO ANALGESIA

Can cause abstinence syndrome after prolonged use

Mechanism in the limbic system via the inhibitory neurotransmitter, gamma aminobutyric acid

(GABA)

DIAZEPAM (VALIUM)

Sedating, variable amnesia, anxiolytic

Irritating to veins, pain in PIV

Multiple active metabolites

Advantage for prolonged sedation

Disadvantage for rapid arousal

Not recommended for continuous infusion

Half-life 12-24 hrs

Hepatic metabolism

LORAZEPAM (ATIVAN)

Improved amnesia

No active metabolites

Half life 4-12 hours

Metabolized by glucuronyl transferase

Less influence from other drugs

Better preserved in patients with liver

disease

MIDAZOLAM (VERSED)

Rapid onset

Rapid metabolism

Good amnesia

Water soluble, no pain with injection

Half life 2 -4 hours

Hepatic metabolism with renal excretion

Active hydroxy-metabolite may accumulate

Other routes of administration

Oral

Nasal

Rectal

Sublingual

Less absorption requiring increase dosing

MIDAZOLAM

Reports of dystonia and choreoathetosis

post infusion, greater risk in neonates

Heparin decreases protein binding,

increases free drug

Disadvantage cost

20 kg patient

80 $/day compared to Ativan = 30 $/day

BENZODIAZEPINES SIDE EFFECTS

RESPIRATORY DEPRESSION

Less than narcotics, but potentiated with narcotics

Dose related

Reversal Flumazenil - benzodiazepine receptor antagonist

Contraindicated in patients with chronic benzo use for seizures, mixed overdose, TCA’s - may result in seizures

BENZODIAZEPINES SIDE EFFECTS

Choreoathetoid movement disorder

Tolerance

As with narcotics may need to increase dose following 2-3 days use

Dependence

Withdrawal carefully and slowly if on greater than 7-10 days

Signs of withdrawal - tremor, tachycardia, hypertension,

Rapid withdrawal may promote seizures

CHLORAL HYDRATE

Sedative hypnotic agent

Metabolized in the liver to its active form, trichlorethanol

Half life 8-12 hours

Oral or rectal administration

Onset of action delayed

Paradoxical reaction in some older children

Not to exceed 100 mg/kg/day - i.e.: 25mg/kg/q 6 hrs

Caution in children < 3 months or with hepatic dysfunction

BARBITURATES

Sedative

Respiratory depression dose dependent

Negative inotropic effects/vasodilation -

decreased cardiac output

Decreased cerebral O2 consumption

CBF

ICP

Anticonvulsant

BARBITURATES

Useful in patients with increased ICP

Short acting barbiturate useful for

sedation for procedure/imaging in

hemodynamically stable child

Alkaline solution, often incompatible with

TPN or meds.

MAJOR TRANQUILIZERS

Phenothiazine

Thorazine

Butyrophenones

Droperidol

Haloperidol

Common in adult ICU, uncommon in PICU

Side effects hypotension due to alpha blockade

and extrapyramidal effects

At times useful in the difficult to sedate child

KETAMINE

Dissociative IV anesthetic

Good amnesia and somatic analgesia

Anesthetic state classically described as a functional and electrophysiological dissociation between the thalamoneocortical and limbic system

Chemically related to phencyclidine and cyclohexamine

Water and lipid soluble

Quickly crosses blood-brain barrier, < 30 seconds

KETAMINE

Redistribution half-life 4.7 minutes Elimination half-life 2.2 hours Clinical effects evident within one minute, resolution within

15 - 20 minutes of dose Bronchodilation Sialagogue -“promoting the flow of saliva”

Administer with an anticholinergic Atropine or Robinol

Minimal net hemodynamic effect Negative inotrope Central effect - HR, SVR

Good choice in shock or status asthmaticus

KETAMINE

Risk of laryngospasm

Risk of emesis/aspiration

Increases ICP , globe pressure

Seizure inducing

Emergent reactions, hallucinations

Improved with administration of a benzodiazepine

IM: 2 - 4 mg/kg dose q 30 minutes - 1 hour

IV

Intermittent dosing

1 -2 mg/kg dose q 30 minutes to 1 hr

Continuous dosing

1 - 3 mg/kg/hr

PROPOFOL

Sedative/hypnotic

Dose dependent - conscious sedation to

general anesthesia

Rapid onset (20-50 seconds)

Quick recovery ( within 30 minutes of d/c)

Lack of active metabolites

Metabolized in liver

Excreted in urine

PROPOFOL

Lipid emulsion, reports of anaphylaxis

Soybean oil, egg lecithin, and glycerol

Decreased ICP, may lower CPP

Decreased sympathetic tone

Contraindicated in hemodynamically

unstable

Moderate respiratory depression

Pain with injection/infusion site

Improved with use of 1% lidocaine

0.5 mg/kg

PROPOFOL

Neurologic sequela

Opisthotonic posturing

Myoclonic movements

Metabolic acidosis reported with use > 24 hrs

Contraindicated for long term use

Doses

1 - 3 mg/kg induction

20 - 100 mcg/kg/min

Increase infusion rate 5-10 mcg/kg/min increments of 5 - 10 minutes