material management

1. Sedation, Analgesia and delirium
in ICU
Prepared by Dr Tsiyon(OBGYN R3)
Moderator- Dr sirak(MD,Anesthesiologist)

2. outline
–Pain and causes of pain in critically ill
patients
–Pain assesment
–pain management in the ICU
–Sedation in ICU
–Delirium and its management
–Reference

3. • THE ICU EXPERIENCE
• In patients who have been discharged from an ICU,
surveys conducted at 6 months to 4 years after discharge
show that 20–40% of the patients have no recollection of
what happened during their ICU stay .
• One study has reported that 25% of patients with
stressful experiences in the ICU showed symptoms of
post traumatic stress disorder 4 years later

4. Pain in Critically Ill Patients
• Pain is defined as “an unpleasant sensory or
emotional experience
• Surveys indicate that 50–80% of ICU patients experience
pain and discomfort while in the ICU
• Hypernociception- Critically ill patients experience pain
more readily than healthy subjects

5. Common painful procedures in ICU
• Peripheral IV insertion
• Central line insertion
• Peripheral blood draw
• Mouth care
• Eye care
• Turning or mobilization
• NG tube insertion
• Extubation
• Catheter
• ETT, oral airway
• Operation related wound pain for surgical patients

6. What factors influence pain in critically ill patients
during both bed rest and during procedures
• Pain at rest- is influenced by psychological(anxiety,
depression) and demographic (young age, one or more
comorbidities, past hx of surgery)
• Pain during procedures is influenced by preprocedural
pain intensity, the type of procedure, underlying surgical
or trauma diagnosis, demographic factors(young age,
non white intensity

7. Pain Assessment
• Pain scales for patients able to communicate.
Visual Analogue scale (VAS)
Numerical Rating Scale (NRS)
Verbal Rating Scale (VRS)
• Pain scales for patients unable to communicate.
Behavioural Pain Scale (BPS)
Critical Care Pain Observation Tool (CPOT)
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10. Goals of pain control
• The primary goal of analgesia –
 to provide optimal patient comfort.
• Secondary goals include:
 Attenuation of adverse physiologic responses to pain (eg,
hypermetabolism, increased oxygen consumption,
hypercoagulability, and alterations in immune function)
 Prevention of development of chronic pain syndromes.
 Control of anxiety and agitation, particularly in intubated
patients

11. • Pharmacologic Interventions
– Regional analgesia
– Systemic analgesia
Opoid Analgesia
Non-Opoid Analgesia
• Non pharmacological interventions

12. • Regional analgesic therapies target specific areas of
the body, while limiting the systemic effects of
intravenous analgesics.
• Post-traumatic or surgical pain in the thoracic or
upper abdominal areas can be managed by
– intercostal nerve blocks, paravertebral blocks, or epidural
catheters that can improve respiratory mechanics to
reduce the risk of pulmonary compromise or pneumonia .

13. • Epidural analgesia is used for the management of pain
from thoracic, abdominal, or lower extremity operative
procedures, and it can provide bilateral analgesia in
specific dermatomes.
• Extrapulmonary advantages include lower pain scores,
reduced risk of myocardial infarction and dysrhythmias
in high risk patients, and earlier return of bowel
function

14. • OPIOID ANALGESICS — For most patients in the intensive
care unit (ICU), IV opioids are a first-line treatment for non-
neuropathic pain
• All opioids have activity at an opiate receptor, including
agonists, antagonists, and mixed agonist-antagonists.
• Efficacy of opioid analgesics is primarily due to binding to
the mu-opioid receptor

15. Side effects
• Depressed consciousness
• Depression of respiratory drive
• Hypotension
• Histamine release-
– may produce flushing, tachycardia, hypotension, pruritus,
and bronchospasm
• Nausea and vomiting –
• Ileus –
– due to binding to local opiate receptors in the gut,
resulting in ileus and constipation
• Pruritus
• OIH

16. Specific opioid agents
• Morphine- Onset of analgesia is 5 to 10 minutes, with peak
effect occurring in one to two hours.
• has an elimination half-life of three to five hours.
• has several active metabolites that can accumulate in renal
failure.
• One metabolite (morphine 3-glucuronide) can produce
central nervous system excitation with myoclonus and
seizures , while another metabolite (morphine-6-glucuronide)
has more potent analgesic effects than the parent drug .

17. • To avoid accumulation of these metabolites, the maintenance
dose of morphine should be reduced by 50% in patients with
renal failure
• Morphine also promotes the release of histamine, and this
can produce systemic vasodilation and a decrease in blood
pressure

18. • Fentanyl
• Fentanyl is virtually devoid of histamine-releasing
properties. Thus, it is preferred in patients with
hemodynamic instability or bronchospasm
• has more rapid onset of action, less risk of hypotension
• fentanyl has a shorter half-life (two to three hours).

19. • Typically, fentanyl is administered as a continuous IV infusion.
Alternatively, IV boluses may be administered every 30 to 60
minutes, although this method is less convenient and may
allow breakthrough pain to occur.
• It is metabolized in the liver to norfentanyl, an inactive
metabolite that is then excreted in the urine. Renal
insufficiency does not appear to affect its pharmacokinetics

20. • Hydromorphone — is a semi synthetic morphine derivative.
• at least five times more potent, has higher lipid solubility and blood–brain
barrier penetrance, but similar onset, duration, and glucuronide
metabolism as morphine
• Due to its availability in a highly concentrated preparation
(10 mg/mL), this agent may be beneficial in fluid-restricted patients with
high opioid requirements
• its hydromorphone-3-glucuronide (H3G) metabolite causes
neuroexcitatory symptoms and insignificant analgesic effect

21. Cont...
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22. • Remifentanil — is an ultrashort-acting derivative with a rapid onset
of action (<3 minutes), short duration of action - 10 minutes after
cessation of infusion), and analgesic potency approximately equal to
fentanyl.
• is utilized primarily as an infusion (0.05–2 micrograms/kg/min)
Dosing Regimen: 1.5 μg/kg as a loading dose, followed by a
continuous infusion at 0.5– 15 μg/kg/hr,
• metabolized by nonspecific plasma esterases to inactive metabolites.
• when extubation is expected shortly after arrival to the ICU or
frequent neurologic assessments are necessary

23. • Methadone — is a long-acting synthetic opioid with
antagonist properties at the N-methyl-D-aspartate (NMDA)
receptor.
• Has slow metabolism so last much longer but is less useful in
acute pain scenarios
• Because of its availability orally in solution form and its long
half-life, it is ideal for the ICU patient who is expected to need
a long recovery period
• may allow discontinuation of opioid infusion with improved
spontaneous ventilation and eventual weaning from support .

24. • Side effects of methadone include oversedation due to its
long duration of action.
• It prolongs the QTc interval, so Electrocardiographic (ECG)
documentation of the QTc interval is recommended before
and at least every 8 to 12 hours after initiation or increasing
the dose of QTc-prolonging drugs
• Starting doses range from 2 to 5 mg staggered every 8–12
hours.

25. • Meperidine ( Pethidine) is an opioid analgesic that is no longer
favored for pain control in the ICU because of the potential for
neurotoxicity.
• Meperidine is metabolized in the liver to normeperidine, a
metabolite that is slowly excreted by the kidneys (elimination
half-life is 15–40 hours) .
• Its accumulation can produce central nervous system
excitation, with agitation, myoclonus, delirium, and
generalized seizures .

26. NON-OPIOID ANALGESIA
• Ketorolac
• has a proven opioid sparing effect, and the dose of opioid
analgesics can often be reduced by 25–50%
• The recommended dosing regimen for moderate-to-severe
pain in adults is 30 mg IV or IM every 6 hrs, for up to 5 days
• A dose reduction of 50% is recommended for elderly patients
(age ≥65 yrs), and for patients with a body weight <50 kg.
• IM injections can produce hematomas , so IV bolus injection
may be preferred.

27. Ibuprofen
• Ibuprofen is very similar to ketorolac because (a) it is an
NSAID that can be given intravenously, (b) it has an opioid
sparing effect, and (c) it is safe when used for short term pain
control
• The IV dose of ibuprofen is 400-800 mg IV every 6 hrs, with a
maximum daily dose of 3.2 grams .
• Unlike ketorolac, the treatment period for ibuprofen has no
recommended time limit.

28. Acetaminophen
• is an effective analgesic and antipyretic agent used in
critically ill patients to treat fever and/or mild pain
• The recommended dose is 1 gm Q6hr
• Doses are reduced in adult patients with mild or moderate
hepatic insufficiency, chronic alcoholism, malnutrition,
dehydration, or low body weight (≤50 kg).
• Acetaminophen is contraindicated in patients with severe
hepatic insufficiency or severe progressive liver disease

29. Cont...
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30. Ketamine
• provides intense analgesia by blocking N-methyl-D-aspartate
(NMDA) receptors to reduce glutamate release and by binding
to sigma-opioid receptors
• It is employed as a substitute or adjunct for opioid therapy in
selected patients
• Ketamine is occasionally used to help manage opioid
tolerance, withdrawal, hyperalgesia, or neuropathic pain .
• The dose for analgesia without loss of consciousness is 0.2–
0.3 mg/kg iv

31. Gabapentinoids
• The gamma-aminobutyric acid (GABA)
analogues gabapentin and pregabalin
• are anticonvulsant agents indicated in critically ill patients
for management of neuropathic pain (eg, pain from
Guillain-Barré syndrome , diabetic peripheral neuropathy,
spinal cord injury, postherpetic neuralgia, or fibromyalgia)
• The analgesic mechanism of action is probably inhibition
of excitatory neurotransmitter release.

32. Non pharmacological interventions
• Stimuli that might disturb normal diurnal sleep
patterns should be minimized when possible (eg,
noise, artificial lighting, unpleasant ambient
temperature)
• Music therapy for both procedural and non
procedural pain
• Cold therapy for procedural pain

33. Sedation
• Sedation is the process of relieving anxiety
and establishing a state of calm.
• This process includes general supportive
measures (like frequent communication with
patients and families), and drug therapy

34. Goals of sedation in the ICU
–Patient comfort
–Control of pain
–Anxiolysis and amnesia
–Blunting adverse autonomic and hemodynamic
responses
–Facilitate nursing management
–Facilitate mechanical ventilation
–Avoid self-extubation
–Reduce oxygen consumption
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35. Cont.....
Monitoring Sedation
The sedation scales that are most reliable in ICU
patients are:
The Riker Sedation-Agitation Scale (RSAS) and
The Richmond Agitation-SedationScale (RASS)
Other:
– MAAS
– MSAT
– RSS
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36. Remsy sedation Scale (RSS)
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37. The Richmond Agitation-SedationScale
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38. Dr. Anwar 38

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40. BENZODIAZEPINES
• Midazolam and lorazepam are best suited for sedation in the
intensive care unit (ICU) because they can be administered by
either intermittent or continuous infusion and have a
relatively short duration of effect.
• Intravenous diazepam is used less often to sedate patients in
the ICU.
• It can be administered by intermittent infusion, but not
continuous infusion.

41. • Mechanism — Benzodiazepines bind to specific receptors in
the gamma aminobutyric acid (GABA) receptor complex, which
enhances the binding of this inhibitory neurotransmitter.
• Anxiolysis is achieved at low doses. Higher doses are
associated with sedation, muscle relaxation, anterograde
amnesia, anticonvulsant effects, and both respiratory and
cardiovascular depression.
• Coadministration with an opioid analgesic may potentiate
respiratory and cardiovascular depression

42. Properties
• Potency – is determined by its binding affinity for the GABA receptor.
– Lorazepam has the highest binding affinity. Midazolam and diazepam
have progressively lower binding affinities and potencies
• Rapidity of action – is related to how quickly it crosses the blood-brain
barrier.
– Midazolam and diazepam readily cross the BBB because they are the
highly lipophilic. Midazolam has an onset of action of 2 to 5 minutes
following IV infusion and diazepam has a nearly immediate onset of
action. Lorazepam is less lipophilic and, therefore, has a slower onset of
action of 5 to 20 minutes.
• Duration of effect – The duration of effect soon after initiating intermittent
infusions differs from the duration of effect following repeated dosing.

43. Cont....
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44. Advantages
• The advantages of sedation with benzodiazepines include the
following.
1. have a dose-dependent amnestic effect that is distinct from the
sedative effect. The amnesia extends beyond the sedation
period (antegrade amnesia),
2. have anticonvulsant effects which is always a benefit in
critically ill patients.
3. are the sedatives of choice for drug with drawal syndromes,
including alcohol, opiate, and benzodiazepine withdrawal.

45. Adverse effects
• General — Respiratory and cardiovascular depression
• Increased risk for delirium in critically ill patients
• Patients may rarely have a paradoxical reaction to
benzodiazepines. This is characterized by agitation,
restlessness, and hostility .
• Intravenous diazepam may increase the risk of venous
thrombosis and phlebitis at the injection site
• Prolonged sedation

46. DEXMEDETOMIDINE
• is a highly selective, centrally acting alpha-2-agonist with
anxiolytic, sedative, and some analgesic effects.
• Loading-0.23-1mcg/kg/min, maintenance dose 0.2–0.7
micrograms/kg/hour
• It has no deleterious effects on respiratory drive.
• is indicated for initial sedation of mechanically ventilated
patients for up to 24 hours.
• arousal is maintained, despite deep levels of sedation. This
has been called cooperative sedation
• a lower prevalence of delirium

47. Adverse Effects
• Dexmedetomidine produces dose-dependent decreases in
heart rate, blood pressure, and circulating norepinephrine
levels (sympatholytic effect)
• Patients with heart failure and cardiac conduction defects are
particularly susceptible
• Life-threatening bradycardia has been reported, primarily in
patients treated with high infusion rates (>0.7 μg/kg/min)
together with a loading dose

48. PROPOFOL
• It is particularly useful when rapid sedation and rapid
awakening is desirable (eg, patients who require frequent
neurological examinations) because it has a short duration of
effect
• Mechanism- Activation of the central gamma-aminobutyric
acid receptors (GABA[A] receptors) with modulation of
hypothalamic sleep pathways
• has amnesic, anxiolytic, anticonvulsant, and muscle relaxant
effects. It has no direct analgesic effect

49. • Properties — is a highly lipophilic phenol derivative that is
insoluble in water.
• Onset of action – less than one minute
• Duration of effect – 3 to 10 minutes during short-term use
(<48 hours).
– the rapid metabolism of by the liver and elsewhere to
minimally active metabolites, which are renally excreted.
• When the infusion is stopped, awakening occurs within 10–15
minutes,
• has a large volume of distribution and is highly protein bound.

50. • Dosage regimens — A loading dose of 5 mcg/kg/min over five
minutes maintenance 5 -50mcg/kg/min
• Adverse effects — Hypotension is a common consequence,
• Other potential adverse effects - bradycardia, arrhythmias,
neuroexcitatory effects (seizure-like activity, myoclonus,
choreoathetoid movements, meningismus), infections from
contaminated vials or tubing, respiratory acidosis, pancreatitis,
hypertriglyceridemia, anaphylaxis, and green or white discoloration
of urine

51. Propofol infusion syndrome — PRIS is a rare complication
of propofol infusion.
• It is generally associated with high doses (>4 mg/kg per hour or
>67 mcg/kg per minute) and prolonged use (>48 hours)
• Characteristics of PRIS include acute refractory bradycardia, severe
metabolic acidosis, cardiovascular collapse, rhabdomyolysis,
hyperlipidemia, renal failure, and hepatomegaly .
• The incidence of PRIS is unknown, but it is probably less than 1
percent . Mortality is variable but high (33 to 66 percent)
• Treatment involves discontinuation of the propofol infusion and
supportive care

52. ANTIPSYCHOTICS
• Antipsychotics can be used in the intensive care unit (ICU) for
the treatment of hyperactive delirium.
• Haloperidol can be administered intravenously, has a mild
sedative effect, and has relatively low cardiorespiratory
depressive effect
• Mechanism — antagonize dopamine and other
neurotransmitters. However, their precise mechanism of
action remains unknown.

53. • Properties — Haloperidol causes dose-dependent sedation. It
tends to be less sedating and have less anticholinergic activity
than other neuroleptics.
• Rapidity of onset – Haloperidol has an onset of action 15 to 20
minutes after intravenous infusion.
• Duration of effect – duration of effect varies and depends
upon the cumulative dose. Generally speaking, re-dosing may
be needed 4 to 12 hours after symptoms have been controlled
with the initial doses.

54. • Most commonly used regimens are:
• 2.5 to 5 mg intravenous bolus doses administered every six
hours, as needed .
• An initial dose determined by the severity of the agitation.
Examples include a 0.5 to 2 mg intravenous bolus dose for
mild agitation, a 2 to 5 mg intravenous bolus dose for
moderate agitation, and a 10 to 20 mg intravenous bolus
dose for severe agitation. Following the initial dose,
escalate the dose as needed until calm is achieved

55. • Adverse effects — Haloperidol-associated polymorphic
ventricular tachycardia is an uncommon but severe adverse
reaction
• When intermittent infusions are used, the QT interval
should be monitored every shift (ie, every 8 to 12 hours)
• Other potential side effects of haloperidol include acute
dystonic reactions, parkinsonism, tardive dyskinesia, and
neuroleptic malignant syndrome

56. DELIRIUM
• Delirium is extremely common in the intensive care unit
(ICU), occurring in 60–80% of mechanically-ventilated
patients at some point during their ICU stay.
• It is a form of acute brain dysfunction that is characterized
by inattention, cognitive impairment, and alterations in
consciousness.
• Additional, although less common, features of delirium
include hallucinations, delusions, and labile affect.

57. The following subtypes of delirium are recognized
1. Hyperactive delirium is characterized by restless agitation, is
common in alcohol withdrawal, it is rare in hospital-acquired
delirium, accounting for 2% of cases .
2 . Hypoactive delirium is characterized by lethargy and
somnolence. the most common form of hospital-acquired
delirium, and is responsible for 45–64% of cases
3 . Mixed delirium is characterized by episodes of delirium that
alternate between hyperactive and hypoactive forms of the
illness. This type of delirium is reported in 6– 55% of patients
with hospital-acquired delirium

58. • Pathophysiology of delirium
• Recent studies have implicated inflammation and metabolic
derangements of neurotransmitters in the development of
delirium.
• Other factors may include abnormalities in cerebral blood
flow, endothelial dysfunction, pain, and toxic effects of
medications.

59. Non-modifiable risk factors for ICU delirium
• prior comorbidities- prior cognitive impairment is
among the most important
• demographic factors- age
• genetic factors- apolipoprotein E4 is a genetic marker
that has been associated with incident delirium
• the specific acute illness severity

60. Modifiable risk factors for ICU delirium
• the choice of sedative, and most notably the use of
benzodiazepines
• Immobility
• Sleep deprivation
• Unrelieved pain
• Major surgery

61. the two most widely used, easily administered, valid, and
reliable tools include
– the Confusion Assessment Method-ICU (CAM-ICU)
– The Intensive Care Delirium Screening Checklist (ICDSC) .
• The CAM-ICU defines delirium in terms of the four DSM-V
diagnostic features.
• Delirium is deemed present when a patient displays
– an acute change or fluctuating course of mental status
(Feature 1),
– inattention (Feature 2), and
– either an altered level of consciousness (Feature 3), or
– disorganized thinking (Feature 4).

62. • The ICDSC contains eight items based on DSM criteria and
 features of delirium including
 altered level of consciousness,
inattention, disorientation,
 hallucination or delusion,
psychomotor agitation or retardation,
 inappropriate mood or speech,
 sleep/wake cycle disturbance, and
symptom fluctuation.

63. • The scale is completed based on information collected from
an entire 8-hour period or from the previous 24 hours.
• Each item is scored as either 1 (present) or 0 (absent).
• A total score of 4 or greater is considered to indicate the
presence of delirium.

64. Therapeutic strategies
Identify and remove cause of delirium
• T- Toxic situations and Toxic medications
• H- ‘Hypo’ and ‘Hyper’ states
• I – Infection and
– Immobilization
• N- Non-pharmacological reasons
– Neurologic reasons
• K - K+ (potassium)

65. Utilize non-pharmacological measures
Non-pharmacological interventions to prevent
and manage ICU delirium—the PEACE acronym
Physiological
Environmental
Activities of daily living
Communication / coordination
Education

66. • DEXMEDETOMIDINE: Sedation with
dexmedetomidine, an alpha-2-adrenergic receptor
antagonist, is associated with fewer episodes of
delirium than lorazepam or midazolam
• This drug provides an alternative to benzodiazepines
for sedation in ICU patients who are at risk for
delirium

67. Reference
• Marino’s ICU book 4th Edition
• Uptodate 2018
• oxford textbook of critical care 2nd edition
• 2018 clinical practice guideline for prevention and
management of Pain, Agitation,delirium, Immobility
and sleep disruption in Adult patients in ICU

68. Thank you