Analgesia and Sedation

in
Post Cardiac Surgery
Presenter:
Dr Nur Liyana Binti Khairuddin

Supervisor:
Dr Ani Suraya Bt Abdul Ghani
OUTLINE

Introduction
Pain Assessment
Analgesic and Sedative Agents
Analgesia and Sedation Strategy
Weaning
INTRODUCTION
 INTRODUCTION
Major goals for postoperative sedation and analgesia in infants and
children undergoing cardiothoracic surgery is
- to alleviate pain
- to aid the transition of patients from the intensive care unit to home.

The type of agents used for paediatric sedation varies with the medical
needs of the patients.

children need to be comfortable, non-agitated and pain free

 Ideal sedative analgesic agents should have
- a rapid onset and offset of action
- be nontoxic
- Non-cumulative
- Non-addictive
- have minimal interactive effects with other drugs.

Ideal sedatives should provide the patient with cardiorespiratory

stability and be cost effective.
Complex Maladaptive Process Following
Cardiac Surgery And Cardiopulmonary Bypass

Altered glucose homeostasis

Metabolic acidosis
Salt and water retention
Catabolic state and protein breakdown
Lipolysis

Associated with prolonged mechanical ventilation, ICU stay and ↑

morbidity and mortality
 FAST TRACK

Stable post operative hemodynamic

Uncomplicated surgery – PDA ligation, ASD closure, glen shunt

May need analgesia only without sedation.

 ROLES OF SEDATION

Allay anxiety and distress

Attenuation of stress response

Promote synchrony with mechanical ventilation

Minimize cardiorespiratory works

Reduces metabolic rate and oxygen demand

ASSESSMENTS
SEDATION SCORE

0 Awake, alert

1 Mild, awake instantly to call

2 Drowsy, arouse with shaking

3 Very drowsy, difficult to arouse

S Sleeping
PAIN ASSESSMENTS TOOLS
AGENTS
SEDATIVE AGENTS ANALGESIC AGENTS
Benzodiazepine Opioids
Chloral hydrate Acetaminophen
Propofol ( in adult)

BOTH
Dexmedetomidine
Ketamine

Should be select based on

- DISEASE STATE
- DESIRED LEVEL
- CARDIAC STATUS
- RESPIRATORY STATUS
ANALGESIA AND SEDATION
AGENTS
 DEXMEDETOMIDINE (PRECEDEX)
Alpha-2 adrenergic agent
either as a sole agent or in conjunction with opioids and benzodiazepines.

6 x more potent than clonidine

Indication – procedural sedation and sedation in ICU

Dose
- 1mcg/kg slow bolus and 0.2-0.7mcg/kg/hr for infusion
- 1amp = 200mcg
- 200mcg/ 50cc (1cc = 4mcg) children
- 100mcg/50cc (1cc=2mcg)
Properties sedative, anxiolytic
analgesic and lack of adverse respiratory effects
Pharmacokinetic - 94% protein-bound
- undergoes hepatic elimination

- rapid distribution phase - 6 min

- elimination half-life of 2 hours
Pharmacodynami CNS - sedative effects
cs
- Lower MAP and  reduces the cerebral
perfusion pressure

- has cerebral vasoconstricting properties

 will decrease cerebral blood flow.

- lowers the shivering threshold 

effective in treating postoperative
shivering
Pharmacodynamic CVS - Initial increase in blood pressure and
s decrease in heart rate results from
stimulation of peripheral postsynaptic
alpha-2b adrenergic receptors which results
in vasoconstriction.

- The second phase of decrease in blood

pressure and heart rate results from the
central presynaptic alpha 2a adrenergic
receptors stimulated by sympatholysis.

- Cardiac output decreases, bradycardia and

sinus arrest.

- anti-arrhythmic effect in the context of

junctional ectopic tachycardia.
Causes bradycardia, hypotension and hypertension (is associated with
rapid bolus dose administration and large doses.)

Close monitoring of circulatory dynamics and judicious titration is

recommended

Use in precaution, in patient with hepatic impairment

 KETAMINE
Phenyl cyclidine derivative
Lower doses - anxiolytic and analgesic effects.
Higher doses - sedation and dissociative anaesthesia and is used as
an anaesthetic agent for short painful procedures.

Doses:
IV: 1–2 mg/kg.
IM: 3–4 mg/kg
IV infusion: 10–40 mcg/kg/min.
- 30mg/kg in 50cc (1cc/hour = 10mcg/kg/min)
Pharmacokinetic - Excretion via kidneys as conjugated metabolites

- Rapid onset 3–5 min

- Elimination half life 3 hours.
Pharmacodynami CNS - Produce type of catalepsy
cs  open eyes with nystagmus and intact
corneal reflexes.

- Avoided in intracranial hypertension 

dilates cerebral blood vessels.

CVS Tachycardia with increased cardiac output

and increased BP
 sympathomimetic action from central
stimulation
Pharmacodynamic Lungs - Minimal effects on PVR
s - safe in PAH

- Bronchodilator and hence useful in

reactive airways.

Side effects - Depression of respiration and apnea may occur

following too rapid IV administration.

- Delerium, hallucinations and night mares (combine

with benzodiazepine)

- Recovery from ketamine anaesthesia may be

associated with restlessness, agitation, and
disorientation.
 CLONIDINE
Centrally acting alpha-agonist agents
Stimulates alpha 2 and imidazoline receptor. Also effective at blocking
opiates withdrawal symptoms
Second line for analgesia and sedation
Withdrawal benzodiazepine and opioids

50% metabolised in liver , undergoes enterohepatic recirculation

65% excreted in the urine

Dose range: 1-2mcg/kg TDS

Half life: 6-12hours
Hypotension, bradycardia, drowsiness, constipation, restlessness.
ANALGESIC AGENTS
OPIOIDS
Fentanyl, remifentanil, and morphine
most commonly used opioids during general anesthesia and are
continued in the postoperative period for sedation.

Properties: analgesia, and they also produce sedation but do not

provide any amnesia.

seldomly used as a sole agent except when used in high doses

during certain cardiac procedures or with critically ill patients.

When used in the ICU it is better to administer continuous infusions

to provide a constant serum concentration rather than on a PRN
basis
Opioids bind to stereospecific opioid receptors in the central nervous system and peripheral
tissues
resulting in decreased neurotransmissions through various mechanisms, and ultimately
analgesia.
The Mu-1 receptor produces analgesia whereas the Mu-2 receptor has
some analgesic effect but is responsible for hypoventilation,
bradycardia, constipation, urinary retention, and physical dependence.

Kappa receptor activation has mild analgesic properties; opioid

agonists–antagonists often act at these receptors but can also result in
dysphoria, which gives it a low abuse potential.

Delta receptor activation is thought to modulate the activity of the Mu

receptors, and therefore, its activation has similar effects as Mu
receptor activation.
Respiratory - Induce a dose dependant respiratory depression
 apnea, decreased response to PaCO2 and hypoxia,
decreased cough reflex.
CVS Tachycardia with increased cardiac output and increased BP
 sympathomimetic action from central stimulation

Except in morphine – morphine’s histamine release may lead

to large decrease in SVR

Muscle rigidity - centrally mediated muscle contraction occur after large

bolus dosing
- affects mainly abdomen and chest wall
- can lead to inability to ventilate.

- Muscle rigidity can be treated by the administration of

neuromuscular relaxants or opioid antagonist.
Nausea and - Direct stimulation of the chemoreceptor trigger zone and by
vomiting decreased motility on the intestinal tract.
- May also cause biliary colic secondary to sphincter of Oddi
contraction.
Urinary retention - Secondary to the contraction of the vesical sphincter.

Physical - Tolerance and physical dependence can develop with repetitive

dependence opioid usage.

Constipation - Chronic use of all opioids.

- Also one of the few side effects that a person does not develop
tolerance to, and therefore, all patient receiving long-term opioids
should be on a bowel regime.
 MORPHINE

Pharmacokinetic - Rapid onset (15–30 min) after IV and IM administration

- Lasts up to 4 hours

- Slower onset is due to its relatively poor lipid solubility which

slows down it penetration into the CNS and gives it a smaller
volume of distribution.

- Elimination half life is 115 mins.

- Metabolized in the liver by conjugation to glucuronic acid to

form morphine
- 3-glucuronide and morphine-6-glucuronide which is an active
metabolite.
- May accumulate in patients with renal disease leading to a
prolonged morphine effect and potential respiratory
depression.
 MORPHINE

Dose IV bolus for acute pain (0.1–0.2mg/kg)

continuous infusion
(10-40mcg/kg/hour)
1/2BW in 50cc (1cc/hour = 10mcg/kg/hour)

Side effects Hypotension and histamine release (prevented by minimizing

size and speed of bolus dose and keeping the patient supine),
nausea, and vomiting.
 FENTANYL

Fentanyl is an extremely potent synthetic opioid

100 times as strong as morphine
Accumulated dose of >1.6 mg/kg or >5 days of infusions
are associated with developing withdrawal syndrome

Pharmacokinetic - rapid onset and shorter duration of action

- high lipid solubility

- Elimination half life - 180–220 min (slightly longer than

morphine)  due to its large volume of distribution.

- Metabolized – liver

- Break down products can accumulate in renal failure which

may result in poor pain control and delirium.
 FENTANYL

Dose 1ml = 10mcg (200mcg in 20cc)

Starts with 1-2mcg/kg/hour
Mainly used as infusion

Side effects Potent respiratory depression, bradycardia, and muscle

rigidity
 REMIFENTANYL
Potent synthetic opioid and structurally similar to fentanyl
it has ester link-ages that allow for rapid hydrolysis to inactive metabolites
by blood and tissue nonspecific esterases.
300x more potent than morphine

Pharmacokinetic - ultra-short acting opioid

- no accumulation and an elimination half life of 10–20 min
- no matter how long the infusion time or how large the
dose used
Dose - IV for acute pain (1μg/kg IV q5 min)
- Continuous infusion (0.1–1μg/kg/min).

Side effects - Potent respiratory depression, bradycardia and

hypotension (may enhance the cardiac depressant effects
and muscle rigidity of other medications).
SEDATIVE AGENTS
 MIDAZOLAM

Benzodiazepines.
Have anxiolytic, anticonvulsant, hypnotic and amnestic
properties.
Cause myocardial depression.
To be used in caution in low cardiac output patients.
Tolerance and dependence are known to occur after
prolonged usage

Bolus 0.1mg/kg – 0.5mg/kg

Infusion: 1-4mcg/kg/min
3mg/kg in 50cc (1cc/hour = 1mcg/kg/min
 LORAZEPAM

Doses:
0.02-0.06mg/kg (adult 1-3mg) 8- 24H oral.
IV: 0.05-0.2mg/kg over 2 min then 0.01-0.1mg/kg/hour

Onset PO: 20–30 min

Duration 4-8H

Elimination half life is approximately 18 hours

 CHLORAL HYDRATE

Anxiolytics, sedatives and hypnotics

8 -10mg/kg or 250 mg/m2 6-8H PO (max 500mg

q8h).
Sedation for procedures: 25–50 mg/kg PO
(hypnotic effect)

Onset 15–30 min

Duration of action 60–120min
ANALGESIA/SEDATION STRATEGY
SHORT (1-2 days) well , simple procedure
- PDA ligation, ASD closure, Coa
repair, glenn shunt
INTERMEDIATE - Significant heart failure
(3-5 days) - pulmonary hypertension
Large VSD, AVSD, TOF repair
PROLONG (> 5days) - Comorbids i.e. Down
Syndrome, chronic lung
disease, prolong oxygen
dependency
- unstable hemodynamic –
severe LCOS, severe
Analgesia , low dose sedation
- IVI Precedex
- IVI Precedex + Morphine
- IVI morphine + midazolam
- IVI morphine
- + regular PCM + oral analgesia
(oral morphine, oral chloral
hydrate)
IVI Precedex + Morphine
IVI Precedex + Fentanyl
IVI Midazolam + Fentanyl
IVI Midazolam +Morphine
Oral benzodiapzepine/opiods –
reduce need for IVI medication
WEANING SEDATION
 WEANING SEDATION
When used continuously for periods of longer than 5 days
- tolerance and physical dependence can develop to some of the drugs
used to provide pain relief and sedation e.g. opioids and benzodiazepines.

Sudden discontinuation or reduction in dose of these drugs can cause

‘withdrawal symptoms’, which can include diarrhoea, anxiety, sweating,
tremors and tachycardia.

Potentially, withdrawal symptoms can prolong recovery and length of stay,

as well as being distressing to the child and family.
 Signs and Symptoms of Withdrawal
Symptoms
CNS Irritability GI Disturbances Autonomic Dysfunction
Poor sleep pattern Diarrhea Sweating
Tremors Vomitting Fever
Muscle spasm/aches Abdominal pain Yawning
Irritability Uncoordinated suck/ Hiccups
Hallucinations swallow Goosebumps/ chills
Dilated pupils Gagging Increased secretions
Seizures Tachycardia
Tachypnea
Hypertension
 To add sy morphine 0.1mg/kg QID once patient
taking orally.

+/- sy lorazepam 0.03mg/kg QID (equivalent to IVI

midazolam 1mcg/kg/min) or
0.06mg/kg QID (equivalent to IVI midazolam
2mcg/kg/min)

+/- clonidine 1-2mcg/kg 8Hly- 6Hly

+ sy chloral hydrate 10mg/kg/dose 6Hly

On infusion for < 5days

- Turned off
- Monitored for signs of withdrawal for the next 48
hours
 Weaning IVI sedation and IVI analgesia
Duration >5days –
Wean off if WAT score persistently <3 /no withdrawal

Weaning IVI Fentanyl  change to IVI morphine – WAT

score
To cut down by 0.1cc every
shift or BD or per day
 Monitor withdrawal symptoms, WAT score

If >3, give bolus IV 0.1mg/kg of Morphine +/- 0.1mg/kg

of midazolam

Increase back infusion to higher previous rate before

symptoms of withdrawal appeared

+/- chloral hydrate if not already on (10mg/kg 6-8Hly)

+/- clonidine if not already on (1-2mcg/kg 8Hly)

Restart weaning when withdrawal symptoms have

been adequately controlled for 24 hours
 Order of weaning:
Opiods  Benzodiazepine  Chloral hydrate  Clonidine
** Opiods and benzodiazepines may also be weaned in alternating
fashion

Oral Lorazepam weaning frequency:

5-10days: wean frequency of dosing every 24 hours

( i.e. 6Hly  8Hly  12Hly  once daily then stop)

10 days: wean frequency of dosing every 48 hours

( i.e. 6Hly  8Hly  12Hly  once daily then stop)
 Weaning adjuncts:
Chloral hydrate 10mg/kg/dose 6-8Hly

If given regularly for >5 days,

reduce wean frequency of dosing every 24 hours
(i.e. 6Hly  8hly  12hly  once daily then stop)
 Weaning adjuncts:
Clonidine1-2mcg/kg/dose 6-8Hly
This should be the last drug to wean.
Can help to fascilitate weaning of opioids and benzodiazepines

<7 days - < 4mcg/kg/day – stop without weaning

<7 days - >4mcg/kg/day OR > 7days regardless of dose

Wean down to 1mcg/kg/dose TDS – QID
Then wean frequency of dosing every 24 hours
(i.e. 6Hly  8hly  12hly  once daily then stop)

Monitor blood pressure 6Hly while weaning clonidine.

If BP increases by 50% from the previous 24 hours consider
slowing the rate of weaning and increase dose to previous higher
dose before symptoms of withdrawal appeared for 24-48 hours
and start weaning again.
 THANK YOU

REFERRENCES:

Critical Care In Children With Heart Disease, Ricardo A. Munoz

Manual of Paediatric Cardiac Intensive Care,Pre and post operative
guidelines, Manoj Luthra
Manual of Paediatric cardiac Intensive Care, Prashant Shah