4. Introduction
Patient often on
mechanical ventilation,
Can be extremely upset
about their condition and
their surroundings;
In discomfort from
injuries, immobility;
• indwelling catheters; and
emotionally stressed.
5. Why Sedation and Analgesia?
Relief from fear and anxiety
Relief of pain
Reduction of awareness
Need for a good nights sleep
To cope with technology!!
7. Stress Response to Pain
Sleep deprivation affects
up to 50% of ICU patients
Agitation occurs at least
once in 71% of patients in
a medical-surgical ICU
9. Properties of the ideal sedative
Rapid onset of action with rapid recovery
No drug accumulation
Be easy to titrate
No tachyphylaxis or withdrawal symptoms,
No hemodynamic instability
Inexpensive
No single drug has all of these properties
Combination of drugs
10. Approach to Sedation & Analgesia
Define the problem
Identify and treat underlying
physiological abnormalities
Estimate the duration of
treatment required
Choose an appropriate drug
11. Approach to Sedation & Analgesia
Non Pharmacological therapy
Pharmacological therapy
15. Opioid Receptors
µ (mu): OP3a,OP3b
– Primary action site of all opioids
– Analgesia,sedation,euphoria,respiratory
depression
– Distribution: CNS and GI
– Linked to abuse/dependence
κ (kappa): OP2a,b,c analgesia,
psychotomimesis and dysphoria
δ (delta): OP1 analgesia, antitussive, for
endogenous peptides
15
Decrease in neurotransimission
16. Agent
Half
Life
Metabolic
Pathway
Active
Metabolites
Adverse
Effects
Intermittent
Dose
Infusion
Dose
Range
Morphine 3 – 7
hrs
Glucuronidation Yes
Sedation in
renal failure
Histamine
release
0.01 – 0.15 mg
/ kg IV
0.07–0.5
mg/kg/hr
Codeine 3 Hrs Demethylation
and
glucuronidation
Yes
(analgesia,
sedation)
Lacks
potency,
histamine
release
Not
recommended
Not
recommen
ded
Fentanyl 1.5–6
hr
Oxidation No metabolite
parent drug
accumulates
Rigidity
with high
doses
0.35–1.5 μg/kg
i.v. q 0.5–1 hr
0.7–10
μg/kg/hr
Pethidine 3 – 4
hrs
Demethylation
and
hydroxylation
Yes
neuroexcitatio
n, especially in
renal
insufficiency or
high doses
Avoid with
MAOIs and
SSRIs
Not
recommended
Not
recommen
ded
Remifent
anil
3–10
min
Plasma
esterase
None ---- ------ 0.6–15
μg/kg/hr
75 – 200 times as potent as morphine
Morphine 3 glucuronide
Morphine 6 glucuronide
Accumulates in renal failure
Can cause hypotension
No histamine release
Hence useful in hemodynamically
unstable patient
Norpethidine
17. Opioid Side Effects
Respiratory depression- dose dependent
Hypotension – BZD administered concomitantly
Depressed level of consciousness
Intestinal hypomotility
18. NSAIDs
Nonselective, competitive inhibition of
cyclooxygenase, a critical enzyme in the
inflammatory cascade.
Renal failure especially in hypovoluaemic or septic
patients
Risk of gastro-intestinal bleeding.
Acute bronchospasm.
19. NSAIDs
Ketorolac
Half life - 2.4 – 8.6 hrs
Metabolized by kidney
15–30 mg i.v. q 6h,
Avoid more than 2 days
Diclofenac
Safest route – rectal
25 – 50 mg q 8h
20. Acetaminophen
Role limited to relieve mild pain
In combination with an opioid it produces a
greater analgesic effect than higher doses of the
opioid alone
Large doses can cause hepatotoxicity
Dosage - less than 2 g per day for patients with a
significant history of alcohol intake or poor
nutritional status and less than 4 g per day for
others
21. Drug Administration Techniques
Preventing pain is more effective than treating
established pain
Drugs administered on an “as needed” basis,
delivers less than the prescribed dose
Administer analgesics on a continuous or
scheduled intermittent basis, with supplemental
bolus doses as required
26. Context-Sensitive Half-Life
The difference between the concentration
associated with adequate sedation and the
concentration associated with return of an
appropriate level of consciousness
The effect of lorazepam is shorter-lived than that of
midazolam because the concentration “decrement”
is less for lorazepam than for midazolam.
Pohlman et al: Crit Care Med 1994
27. Benzodiazepine Administration
Titrate to a predefined endpoint
“As needed” doses may be adequate
Patients requiring frequent doses may benefit
from a continuous infusion
Continuous infusions may cause accumulation
of parent drug or its active metabolites
producing inadvertent over sedation
28. Propofol
Intravenous, general anesthetic
Rapid onset ( 1 -2 min) and short
duration ( 10 – 15 min) of
sedation
It is rare for the effect to last
longer than 60 minutes after the
infusion
Kinetics unchanged in renal or
hepatic dysfunction
29. Propafol
Hypnotic agent
Potent anxiolytic
potent amnestic agent
Has no analgesic properties
Apnea often occurs after a loading dose of
propofol (25% incidence)
Significant decreases in blood pressure
30. Propafol
Prolonged use (>48 hours) of high doses (>66
μg/kg/min infusion) associated with
lactic acidosis
bradycardia
hypertriglyceridemia (a lipid carrier )
Doses >83 μg/kg/min associated with an
increased risk of cardiac arrest in adults
Propofol infusion syndrome
31. Ketamine
Phencyclidine derivative
Acts by stimulation of NMDA receptors
Profound dissociative state
profound analgesia
maintain a protective cough reflex
Improves BP -Ideal for shock patients
Bronchodilator – may be used to treat severe
acute asthma
32. Ketamine- side effects
Emergence delirium
Severe hallucinations
Not to be used in high ICP patients
Releases catecholamines – can cause
tachycardia, hypertension
Dose : 25 -50 mg IV bolus followed by 10 – 30
mg /hr infusion
33. Neuroleptics
Chlorpromazine
Haloperidol
result in a state of tranquility, and patients often
demonstrate a detached affect
No amnesia or analgesia
Stabilizes cerebral function by antagonizing
dopamine-mediated neurotransmission at the
cerebral synapses and basal ganglia
34. Neuroleptics
Haloperidol
- lesser sedative effect and lower risk of
hypotension than chlorpromazine
- The half-life is approximately 2 hours
- Dosing – 2mg bolus followed by repeated
doses (double the previous dose) every 15–
20 minutes while agitation persists
- no respiratory depression
- mild hypotension
35. Adverse Effects of Haloperidol
QT prolongation leading to ventricular
dysrhythmias, including torsades de pointes
Extrapyramidal symptoms
Neuroleptic malignant syndrome
37. Ramsay Sedation Score
Awake levels:
anxious or agitated or both 1
co-operative, orientated and tranquil 2
responds to commands only 3
Asleep levels:
brisk response to a light glabellar tap 4
sluggish
response to a light glabellar tap 5 no
response to loud auditory stimulus 6
Adequate
38. Complications related to sedative
administration
critically ill patients exhibit unpredictable
alterations in Pk & Pd profiles
drug accumulation result in prolongation
of mechanical ventilation and ICU
length of stay
mask the development of intracranial,
intrathoracic, or intra-abdominal
catastrophes
may experience withdrawal symptoms
39. Wake up call
daily interruption of continuous
sedative infusions
reduced the duration of
mechanical ventilation and
intensive care by 2.5 days and
3.5 days, respectively.
N Engl J Med 2000;342:1471-7.)
DAILY INTERRUPTION OF SEDATIVE INFUSIONS IN CRITICALLY ILL
PATIENTS UNDERGOING MECHANICAL VENTILATION
40. Wake up call
daily interruption of continuous
sedative infusions
the number of diagnostic
studies to investigate
unexplained alterations in
mental status was reduced from
27% to 9%, and
the total amount of Sedatives
administered was decreased.
N Engl J Med 2000;342:1471-7.)
DAILY INTERRUPTION OF SEDATIVE INFUSIONS IN CRITICALLY ILL
PATIENTS UNDERGOING MECHANICAL VENTILATION
41. Sedation protocol
Mean ventilator time decreased
by 2.1 days from 7.4 days before
intervention to 5.3 days after.
Mean stay decreased by 1.0 day
(–0.9 to 2.9 days) from 9.3 days
to 8.3 days.
No accidental extubations or
other incidents were identified.
Brook et al
Guttorm Brattebø
46. Pancuronium
Long acting
Vagolytic – causes increase in heart rate
Active metabolite
Prolonged effects in renal failure and cirrhosis
Dosage – 0.06 – 0.1mg/KG
47. Vecuronium
Intermediate acting
Not vagolytic
50% of drug excreted in bile, 35% renally
excreted
Dose: 0.08 – 0.1 mg/kg, 25 – 30 mins
More commonly associated with prolonged
blockade after discontinuation
Higher risk of prolonged blockade when
combined with steroids
49. Atracurium
Intermediate acting
Minimal cardiovascular effects
Histamine release at high doses
Inactivated by ester hydrolysis and hoffmann
degradation
Breakdown product Laudonosine associated with
CNS excitation, concerns of seziures in patients
with hepatic failure
Requires continuous infusion 10 – 20
ug/kg/min
50.
51. Monitoring Neuromuscular Blockade
Combination of visual tactile and electronic
monitoring
skeletal muscle movement and respiratory effort
forms the foundation of clinical assessment
TOF stimulation most commonly used form of
electronic monitoring
53. Prolonged Recovery From NMBAs
More common with steroid-based NMBAs
Due to the accumulation of NMBAs or
metabolites
time to recovery of 50–100% longer than
predicted
Drug intractions, hypermagnesemia, metabolic
acidosis, hepatic or renal failure may be cause
54. Acute Quadriplegic Myopathy Syndrome
(AQMS)
Devastating complications of NMBA therapy
Diffuse weakness that persists long after the
NMBA is discontinued
Global motor deficit
Decreased motor reflexes
Higher risk with concurrent administration of
steroids, aminoglycosides, cyclosporine
Acute asthma
55.
56. Practice Parameters in Sedation &
Analgesia
Pain assessment and response to therapy should
be performed regularly by using a scale
Fentanyl is preferred for a rapid onset of analgesia
Fentanyl is preferred for patients with
hemodynamic instability or renal insufficiency
Morphine preferred for intermittent therapy
because of its longer duration of effect
Jacobi J et al: Crit Care Med; 30, 1 2002
57. Practice Parameters in Sedation &
Analgesia
Sedation of agitated critically ill patients should
be started only after providing adequate
analgesia and treating reversible physiological
causes
Midazolam or diazepam should be used for
rapid sedation of acutely agitated patients.
Propofol is the preferred sedative when rapid
awakening is important
Jacobi J et al: Crit Care Med; 30, 1 2002
58. Practice Parameters in Sedation &
Analgesia
Midazolam is recommended for short-term use
only, as it produces unpredictable awakening and
time to extubation when infusions continue longer
than 48–72 hours.
Lorazepam is recommended for the sedation of
most patients via intermittent i.v. administration or
continuous infusion.
Ttitrate sedative dose to a defined endpoint with
systematic tapering of the dose or daily interruption
to minimize prolonged sedative effects.
Jacobi J et al: Crit Care Med; 30, 1 2002
59. Practice Parameters
NMBAs should be used for an adult patient in an
ICU to manage ventilation, manage increased
ICP, treat muscle spasms, and decrease oxygen
consumption only when all other means have
been tried without success
Murray J M et al: Crit Care Med; 30, 1 2002
60. Practice Parameters
The majority of patients can be managed
effectively with pancuronium.
Cisatracurium or atracurium is recommended for
patients with significant hepatic or renal disease
Patients receiving NMBAs should be assessed
both clinically and by TOF monitoring, with a goal
of adjusting the degree of neuromuscular
blockade to achieve one or two twitches.
Murray J M et al: Crit Care Med; 30, 1, 2002
