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 Airway Neurological

failure

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

PCA dosing
Initial

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

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

mcg/kg/hr recommended in children less than 12

IV continuous dosing
1-2

Transdermal delivery system available

Not

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
Full

- Nalaxone (Narcan)

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

Other routes of administration

Oral Nasal Rectal Sublingual

Less absorption requiring increase dosing

Active hydroxymetabolite may accumulate

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, TCAs - 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 0.5

with use of 1% lidocaine

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