This document provides information on monitoring and managing pain, agitation, and delirium in the ICU. It defines pain, agitation, and delirium and describes scales to monitor them. It discusses various drugs used for analgesia, sedation, and anxiety including opioids, benzodiazepines, propofol, dexmedetomidine, and their dosages, effects, and adverse reactions. It emphasizes the importance of light sedation levels and daily sedation interruption protocols.

1. ART OF SEDATION & ANALGESIA IN
ICU
Dr. Ashish Ranjan
Senior resident
ESICPGIMSR,New Delhi

2. LEARNING OBJECTIVES
 Definitions of Pain agitation and delirium
 How to monitor these
 Drugs and their dosing
 Adverse reactions
 Pain,Agitaion,Delirium(PAD) bundles

4. PAIN
 Pain is defined as “an unpleasant sensory or
emotional experience”, which highlights the
subjective nature of pain.
 The pain sensation can be described in terms of
intensity, duration, location, and quality
 but pain intensity is the parameter most often
monitored because it reflects the “unpleasantness”
of pain.

5. MONITORING OF PAIN
 Pain Intensity Scales
There are 6 different pain intensity scales.2 are
important
 1. When patients can reliably self-report pain, the
Numerical Ranking Scale can be used for pain
assessment
 2. When patients are sedated and on a ventilator,
the Behavioral Pain Scale (BPS) recommended for
pain assessments
 Adequate pain control = SCORE 5

6. NUMERICAL RATING SCALE
BEHAVIOURAL PAIN SCALE

7. OPOID ANALGESIA
 Stimulation of opioid receptors produces a variety
of effects, including analgesia, Sedation, euphoria,
pupillary constriction Respiratory depression,
bradycardia, constipation, nausea, vomiting, urinary
retention, and pruritis
 Fentanyl has replaced morphine as the most
popular opioid analgesic in ICUs
 The advantages of fentanyl over morphine include
a more rapid onset of action (because fentanyl is
600 times more lipid soluble than morphine), less
risk of hypotension (because fentanyl does not
promote histamine release) and the absence of
active metabolites.

9. REMIFENTANIL
 Remifentanil is an ultra-short acting opioid that is given by
continuous intravenous Infusion
 Dosing Regimen: 1.5 μg/kg as a loading dose, followed by a
continuous infusion at 0.5– 15 μg/kg/hr
 Analgesic effects are lost within 10 minutes after stopping the
drug infusion.
 The short duration of action is B/C it is broken down by
nonspecific esterases in plasma. Because drug metabolism
does not take place in the liver or kidneys, dose adjustments
are not necessary in renal or hepatic failure.
 Short duration of action is most advantageous in conditions
that require frequent evaluations of cerebral function (e.g.,
traumatic head injuries).
 The abrupt cessation of opioid activity can precipitate acute
opioid withdrawal which can be prevented by combining
remifentanil with a longer-acting opioid.

10. PCA
For patients who are awake and capable of
drug self-administration, patient-controlled
analgesia (PCA) can be an effective method
of pain control, and may be superior to
intermittent opioid dosing.
The PCA method uses an electronic
infusion pump that can be activated by the
patient. When pain is sensed, the patient
presses a button connected to the pump to
receive a small intravenous bolus of drug.
After each bolus, the pump is disabled for a
mandatory time period called the “lockout
interval,” to prevent overdosing.
When writing orders for PCA, one must
specify the initial loading dose (if any), the
lockout interval, and the repeat bolus dose.
PCA can be used alone or in conjunction with
a low dose opioid infusion.

11. ADVERSE EFFECTS
 Respiratory depression
 Hypotension ,bradycardia
 Intestinal hypomotility-Opioid-induced bowel
hypomotility can be partially reversed with enteral
naloxone (8 mg every 6 hours) without affecting
opioid analgesia
 Vomiting and nausea

12. NON OPOID ANALGESIA
 Only three drugs: acetaminophen, ketorolac, and
ibuprofen are used primarily for pain control in the
early postoperative period.
 They can be used alone for mild pain, but are used
in combination with an opioid analgesic for
moderate-to-severe pain.
 The goal of combination analgesic therapy is to
reduce the opioid dose (“opioid sparing” effect) and
hence reduce the risk of an opioid-related adverse
effect.

14. ANXIETY, AGITATION
 Anxiety and related disorders (agitation ) are
observed in as many as 85% of patients in the ICU
.
 These disorders can be defined as follows.
1. Anxiety is characterized by exaggerated
feelings of fear or apprehension that are sustained
by internal mechanisms more than external events.
2. Agitation is a state of anxiety that is
accompanied by increased motor activity.
.
 The common denominator in these disorders is the
absence of a sense of well-being.

15. 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.

16.  Initial management- conservatively managing the
identifiable cause of distress
 Non-pharmacologic management: Reassurance,
interaction with the patient and reorientation,
family visits, cognitive behaviour therapy
 Sedation: when these are not effective in
controlling the distress

17. AGENTS OF SEDATION IN ICU
Agents causing sedation by their direct effect
 (a)GABA agonists (GABA is one of the most important CNS
inhibitory
system)
(1) Benzodiazepines (diazepam, lorazepam, midazolam)
(2) Propofol
 (b)Alpha 2 agonist
(1) Dexmedetomidine
Agents causing sedation as an adverse effect
 (a) Antipsychotics
(1) Typical – haloperidol
(2) Atypical – risperidone, olanzapine
 (b) Opioids

19. BZD
 GABA- A central nervous system receptors
• Metabolized by the liver, excreted through kidneys
• Reduced clearance in hepatic dysfunction except for
Lorazepam
• Long half life in renal failure- prolonged effect
• Elderly patients clear more slowly
• S/E - respiratory depression and hypotension
Prolonged sedation

20. ADVANTAGES AND DISADVANTAGES
Advantages
 1.Benzodiazepines have a dose-dependent
amnestic effect (antegrade amnesia),
2. Benzodiazepines have anticonvulsant effects
3. Benzodiazepines are the sedatives of choice for
drug withdrawal syndromes, including alcohol,
opiate, and benzodiazepine withdrawal.
 Disadvantages
(a) drug accumulation with prolonged sedation,
and
(b) the apparent tendency for benzodiazepines to
promote delirium.

21. SOLUTION FOR PROLONGED SEDATION
 1.Daily interruption of benzodiazepine infusions
(until the patient awakens) curtails drug
accumulation, and has been shown to shorten the
duration of mechanical ventilation,and reduce the
length of stay in the ICU ).
 2. Titration of benzodiazepine infusions to maintain
light levels of sedation, using routine monitoring
with a sedation scale (SAS or RASS), a standard
practice.
 3. The final solution to the problem is to avoid
benzodiazepines for sedation

22. LORAZEPAM
 Propylene glycol (1,2-propanediol) is the solvent
used
to deliver lorazepam and diazepam IV
Close monitoring of all patients receiving IV
lorazepam or diazepam for early evidence of
propylene glycol toxicity is warranted
 Life threatening iatrogenic complication that is
preventable
 – unexplained anion gap
 – unexplained metabolic acidosis
 – hyperosmolality
 – clinical deterioration

23. PROPOFOL
 Activates GABA receptors & inhibits NMDA
glutamate receptors
 Rapid onset and offset of sedation
 Helpful in patients requiring frequent awakenings
for neurologic assessments and it may facilitate
daily sedation interruption protocols
 Not dependent on hepatic and renal function

24. PRIS
 Propofol infusion syndrome is a rare and poorly
understood condition that is characterized by the
abrupt onset of bradycardic heart failure, lactic
acidosis, rhabdomyolysis, and acute renal failure
 This syndrome almost always occurs during
prolonged, high-dose propofol infusions (>4–6
mg/kg/hr for longer than 24–48 hrs) (53).
 The mortality rate is 30% . Avoiding propofol
infusion rates above 5 mg/kg/hr for longer than 48
hrs is recommended to reduce the risk of this
condition

25. WHICH AGENT TO USE
 Individualize based on patient factors
 Expected duration of ventilation
 Presence of organ failures, hypersensitivity to
drugs
 Clinical pharmacology of the drug in use must be
considered
 Hypoalbuminemia
 Drug interaction due to polypharmacy
 Altered pharmacokinetics and dynamics – drug
accumulation
 Cost and cost-effectiveness

26. HOW TO MONITOR
 Sedation Agitation Scale (SAS)
 Richmond Agitation-Sedation Scale (RASS)
 Observer’s assessment of alertness/sedation scale
 (OAA/S)
 Ramsay sedation scale
 New Sheffield sedation scale
 Sedation Intensive Care Score (SEDIC)
 Motor Activity Assessment Score (MAAS)
 Adaption to Intensive care environment (ATICE)
 Minnesota Sedation Assessment Tool (MSAT)
 Vancouver Interaction and Calmness Scale (VICS)

28. RASS

29.  Light sedation improves outcome (RASS -2 to +1 in
many studies. Varies from trial to trial)
 Shorter ICU stay and ventilation days
 Though light sedation may increase some
physiologic Stress, (increased catecholamine
levels and oxygen consumption) may not be
associated with negative clinical outcomes
 No difference in post ICU psychological outcome
based on
the depth of sedation

30. INTERRUPTION OF SEDATION
 Daily sedation interruption (DSI) defined as short-term
suspension, hold, discontinuation, cessation, or interruption of
intravenous sedatives(continuous infusions or fixed dose
bolus) and, in some cases, analgesic medications”
 To prevent drug bioaccumulation
 Awake state
 Assess whether liberation is possible or not and neurologic
status
 Interruption is done till patient becomes awake, and can obey
simple commands
 Daily interruption of sedation (DSI) may reduce the total
duration of ventilation
Burry L et al. Cochrane Database of Systematic Reviews 2014,
Issue 7. Art. No.:
CD009176

31. DEXMEDETOMIDINE
 Alpha 2 adrenergic agonist
 Similar to clonidine, but more specific
 Does not act on GABA receptors
 Acts on locus ceruleus
 No respiratory depression

32.  Recent meta-analysis: 28 studies (27 publications)
 Trials in general ICU setting – 13
 Loading dose 1 mcg/kg followed by infusion
ranging from 0.1 to 2.5 mcg/kg have been in used
in majority (18 trials)
 Six different comparators: propofol in 11 study,
midazolam in 10, placebo in 5, morphine in 2,
haloperidol and lorazepam in one each
Pasin L, et al. PloS one. 2013;8(12):e82913

35. ADVERSE EFFECT
 Decreases sympathetic activity – may increase
adverse cardiac events Especially in individuals
with autonomic disturbance, elderly, diabetics,
chronic hypertension. Valvular heart disease, heart
blocks, severe CAD, hypotension/ hypovolemia

37. DELIRIUM
 Four domains of delirium: disturbance of
consciousness, change in cognition, development
over a short period, and fluctuation.
 Delirium is defined by the National Institutes of
Health as “sudden severe confusion and rapid
changes in brain function that occur with physical or
mental illness.”
 The most common feature of delirium, thought by
many to be its cardinal sign, is inattention.
 Delirium is a nonspecific but generally reversible
manifestation of acute illness that appears to have
many causes, including recovery from a sedated or
oversedated state

38.  Forms of delirium,
1.Hypoactive and
2.Aagitated (or hyperactive).
3.Mixed delirium.
 The hypoactive form is characterized by inattention,
disordered thinking, and a decreased level of
consciousness without agitation.
 Although the association between delirium and a worse
outcome is clear, a causal relationship has not been
established.
 A diagnosis of delirium is associated with increased
mortality (estimated as a 10% increase in the relative
risk of death for each day of delirium

40. INTENSIVE CARE DELIRIUM SCREENING CHECKLIST
 • Patient must show at least a response to mild or
moderate stimulation. Then score 1 point for each of the
following features :
 – Anything other than “normal wakefulness”
 – Inattention
 – Disorientation
 – Hallucination
 – Psychomotor agitation
 – Inappropriate speech or mood
 – Disturbance in sleep or wake cycle
 – Fluctuation in symptoms
 A score of ≥4 is positive for delirium (with scores of 1 to
3 termed “subsyndromal delirium”)

41. HALOPERIDOL
 Haloperidol produces its sedative and antipsychotic
effects by blocking dopamine receptors in the
central nervous system.
 Following an intravenous bolus dose of haloperidol,
sedation is evident in 10–20 minutes, and the effect
lasts 3–4 hours.
 There is no respiratory depression, and
hypotension is unusual in the absence of
hypovolemia

42. HALOPERIDOL DOSING

43. ADVERSE EFFECT
 The adverse effects of haloperidol include: (a)
extrapyramidal reactions, (b) neuroleptic malignant
syndrome, and (c) ventricular tachycardia.
 1. Extrapyramidal reactions (e.g., rigidity, spasmodic
movements) are dose-related side effects of oral
haloperidol therapy,
 2. The neuroleptic malignant syndrome, an
idiosyncratic reaction to neuroleptic agents that consists
of hyperpyrexia, severe muscle rigidity, and
rhabdomyolysis.
 3. The most publicized risk of therapy with haloperidol is
prolongation of the QT interval on the
electrocardiogram, which can trigger a polymorphic
ventricular tachycardia (torsade de pointes).

46. ABCDE
BUNDLE

47. CONCLUSION
 1. Critically ill patients experience pain in situations that
are not normally painful. This indicates that pain
control is a full-time endeavor in ICU patients.
 2. Unrelieved pain can be a source of agitation, so
make sure that pain is relieved before considering a
sedative drug for agitation.
 3. When a benzodiazepine is used for prolonged (>48
hrs) sedation, attention to preventing drug
accumulation and prolonged sedation can result in a
shorter time in the ICU.
 4. The preventive measures include daily interruption
of drug infusions, or maintaining light sedation using a
reliable sedation scale to guide adjustments in drug
dosage.

48.  4. Consider using dexmedetomidine for sedation,
because this drug allows the patient to be aroused
while still sedated . When arousal is no longer
needed, the patient will resume the prior level of
sedation. This is more like sleep than a drug-
induced stupor.
 5. Finally, communicate with patients (e.g., tell
them what you are going to do before doing it), and
allow some “down time” for patients to sleep.

49. REFERENCES
 Paul Marino,The ICU book.4th edition
 Barr J, Fraser GL, Puntillo K, et al. Clinical practice
guidelines for the management of pain. agitation,
and delirium in adult patients in the intensive care
unit. Crit Care Med 2013; 41:263–306.
 Michael C. Reade et al, Sedation and Delirium in
the Intensive Care Unit ,N Engl J Med
2014;370:444-54.

50. THANKS
FOR
PATIENT
HEARING