Analgesia, Sedation &
Neuromuscular Blockade In ICU
DR.RAGHUNATH ALADAKATTI
APOLLO BGS HOSPITAL
MYSORE
Objective
1. Why to use?
2. Which one to choose?
3. How to use these drugs?
4. What are the problems?
5. Protocols ?
Introduction
“Sedate” – To sooth
Nearly all patients in ICU
require some kind of
“soothing”
Introduction
Patient often on
mechanical ventilation,
Can be extremely upset
about their condition and
their surroundings;...
Why Sedation and Analgesia?
Relief from fear and anxiety
Relief of pain
Reduction of awareness
Need for a good nights slee...
Stress Response to Pain
Tachycardia
Increased myocardial oxygen consumption
Hypercoagulability
Immunosuppression
Persisten...
Stress Response to Pain
Sleep deprivation affects
up to 50% of ICU patients
Agitation occurs at least
once in 71% of patie...
Indications
Analgesia
Anxiety
Dyspnea
To facilitate care
To decrease excess
oxygen consumption
To achieve amnesia
Properties of the ideal sedative
Rapid onset of action with rapid recovery
No drug accumulation
Be easy to titrate
No tach...
Approach to Sedation & Analgesia
Define the problem
Identify and treat underlying
physiological abnormalities
Estimate the...
Approach to Sedation & Analgesia
Non Pharmacological therapy
Pharmacological therapy
Pharmacologic therapy
Analgesics
Sedatives
Neuroleptics
Analgesics
Opioids
NSAIDs
Acetaminophen
Opioids
Naturally Occurring Synthetic
Morphine Codiene Fentanyl Pethidine
Sufentanil
Alfentanil
Remifentanil
Opioid Receptors
µ (mu): OP3a,OP3b
– Primary action site of all opioids
– Analgesia,sedation,euphoria,respiratory
depressi...
Agent
Half
Life
Metabolic
Pathway
Active
Metabolites
Adverse
Effects
Intermittent
Dose
Infusion
Dose
Range
Morphine 3 – 7
...
Opioid Side Effects
Respiratory depression- dose dependent
Hypotension – BZD administered concomitantly
Depressed level of...
NSAIDs
Nonselective, competitive inhibition of
cyclooxygenase, a critical enzyme in the
inflammatory cascade.
Renal failur...
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
Saf...
Acetaminophen
Role limited to relieve mild pain
In combination with an opioid it produces a
greater analgesic effect than ...
Drug Administration Techniques
Preventing pain is more effective than treating
established pain
Drugs administered on an “...
Benzodiazepines
Excellent for relieving anxiety
Potent amnestic agents
Potent sedatives and Induce hypnosis
Benzodiazepines
Benzodiazepines enhance the
inhibitory effects of the
neurotransmitter -aminobutyric
acid (GABA) causing
g...
Agent Onset
of
action
Half life Metabolic
pathway
Active
Metabolite
Adverse
effects
Intermitte
nt dose
Infusion
Dose
Midaz...
Benzodiazepines- side effects
Dose dependent CNS
suppression
Dose dependent centrally
mediated respiratory
depression
Card...
Context-Sensitive Half-Life
The difference between the concentration
associated with adequate sedation and the
concentrati...
Benzodiazepine Administration
Titrate to a predefined endpoint
“As needed” doses may be adequate
Patients requiring freque...
Propofol
Intravenous, general anesthetic
Rapid onset ( 1 -2 min) and short
duration ( 10 – 15 min) of
sedation
It is rare ...
Propafol
Hypnotic agent
Potent anxiolytic
potent amnestic agent
Has no analgesic properties
Apnea often occurs after a loa...
Propafol
Prolonged use (>48 hours) of high doses (>66
μg/kg/min infusion) associated with
lactic acidosis
bradycardia
hype...
Ketamine
Phencyclidine derivative
Acts by stimulation of NMDA receptors
Profound dissociative state
profound analgesia
mai...
Ketamine- side effects
Emergence delirium
Severe hallucinations
Not to be used in high ICP patients
Releases catecholamine...
Neuroleptics
Chlorpromazine
Haloperidol
result in a state of tranquility, and patients often
demonstrate a detached affect...
Neuroleptics
Haloperidol
- lesser sedative effect and lower risk of
hypotension than chlorpromazine
- The half-life is app...
Adverse Effects of Haloperidol
QT prolongation leading to ventricular
dysrhythmias, including torsades de pointes
Extrapyr...
Monitoring
Crit Care 2002, 8:290–298 ©2002
Adequate
Ramsay Sedation Score
Awake levels:
anxious or agitated or both 1
co-operative, orientated and tranquil 2
responds to comm...
Complications related to sedative
administration
critically ill patients exhibit unpredictable
alterations in Pk & Pd prof...
Wake up call
daily interruption of continuous
sedative infusions
reduced the duration of
mechanical ventilation and
intens...
Wake up call
daily interruption of continuous
sedative infusions
the number of diagnostic
studies to investigate
unexplain...
Sedation protocol
Mean ventilator time decreased
by 2.1 days from 7.4 days before
intervention to 5.3 days after.
Mean sta...
Neuromuscular Blockade in
ICU
Indications
Facilitate intubation
Facilitate mechanical ventilation
Control of ICP
Control muscle spasms
Decrease oxygen c...
Neuromuscular Agents
Depolarizing muscle relaxants
Suxamethonium
Non depolarizing muscle relaxants
- Aminosteroidal Compou...
Pancuronium
Long acting
Vagolytic – causes increase in heart rate
Active metabolite
Prolonged effects in renal failure and...
Vecuronium
Intermediate acting
Not vagolytic
50% of drug excreted in bile, 35% renally
excreted
Dose: 0.08 – 0.1 mg/kg, 25...
Rocuronium
Intermediate acting
Very rapid onset of action
Metabolite has only 5 -10% activity of parent
compound
Dose: 0.6...
Atracurium
Intermediate acting
Minimal cardiovascular effects
Histamine release at high doses
Inactivated by ester hydroly...
Monitoring Neuromuscular Blockade
Combination of visual tactile and electronic
monitoring
skeletal muscle movement and res...
Complications
Prolonged recovery
from NMBAs
Acute quadriplegic
myopathy syndrome
(AQMS)
Prolonged Recovery From NMBAs
More common with steroid-based NMBAs
Due to the accumulation of NMBAs or
metabolites
time to...
Acute Quadriplegic Myopathy Syndrome
(AQMS)
Devastating complications of NMBA therapy
Diffuse weakness that persists long ...
Practice Parameters in Sedation &
Analgesia
Pain assessment and response to therapy should
be performed regularly by using...
Practice Parameters in Sedation &
Analgesia
Sedation of agitated critically ill patients should
be started only after prov...
Practice Parameters in Sedation &
Analgesia
Midazolam is recommended for short-term use
only, as it produces unpredictable...
Practice Parameters
NMBAs should be used for an adult patient in an
ICU to manage ventilation, manage increased
ICP, treat...
Practice Parameters
The majority of patients can be managed
effectively with pancuronium.
Cisatracurium or atracurium is r...
Thank You
Sedation & Paralysis in ICU- DR.RAGHUNATH   ALADAKATTI
Sedation & Paralysis in ICU- DR.RAGHUNATH   ALADAKATTI
Sedation & Paralysis in ICU- DR.RAGHUNATH   ALADAKATTI
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Sedation & Paralysis in ICU- DR.RAGHUNATH ALADAKATTI

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  • OUT OF 17 RECEP DESCRIBED IN THE LITERATURE
    MU: ANALGESIABECAUSE EUPHORIC EFFECTS AND + REINF
    Decrease in neurotransimission
  • Sedation & Paralysis in ICU- DR.RAGHUNATH ALADAKATTI

    1. 1. Analgesia, Sedation & Neuromuscular Blockade In ICU DR.RAGHUNATH ALADAKATTI APOLLO BGS HOSPITAL MYSORE
    2. 2. Objective 1. Why to use? 2. Which one to choose? 3. How to use these drugs? 4. What are the problems? 5. Protocols ?
    3. 3. Introduction “Sedate” – To sooth Nearly all patients in ICU require some kind of “soothing”
    4. 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. 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!!
    6. 6. Stress Response to Pain Tachycardia Increased myocardial oxygen consumption Hypercoagulability Immunosuppression Persistent catabolism
    7. 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
    8. 8. Indications Analgesia Anxiety Dyspnea To facilitate care To decrease excess oxygen consumption To achieve amnesia
    9. 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. 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. 11. Approach to Sedation & Analgesia Non Pharmacological therapy Pharmacological therapy
    12. 12. Pharmacologic therapy Analgesics Sedatives Neuroleptics
    13. 13. Analgesics Opioids NSAIDs Acetaminophen
    14. 14. Opioids Naturally Occurring Synthetic Morphine Codiene Fentanyl Pethidine Sufentanil Alfentanil Remifentanil
    15. 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. 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. 17. Opioid Side Effects Respiratory depression- dose dependent Hypotension – BZD administered concomitantly Depressed level of consciousness Intestinal hypomotility
    18. 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. 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. 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. 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
    22. 22. Benzodiazepines Excellent for relieving anxiety Potent amnestic agents Potent sedatives and Induce hypnosis
    23. 23. Benzodiazepines Benzodiazepines enhance the inhibitory effects of the neurotransmitter -aminobutyric acid (GABA) causing generalized depression of the CNS
    24. 24. Agent Onset of action Half life Metabolic pathway Active Metabolite Adverse effects Intermitte nt dose Infusion Dose Midazolam 2–5 min 3–11 hr Oxidation Yes prolonged sedation, especially with renal failure 0.02–0.08 mg/kg q 0.5–2 hr 0.04–0.2 mg/kg/hr Lorazepam 5–20 min 8–15 hr Glucuroni dation None Solvent- related acidosis, renal failure in high doses 0.02–0.06 mg/kg q 2–6 hr 0.01–0.1 mg/kg/hr Diazepam 2–5 min 20–120 hr Desmethyl ation and hydroxylati on Yes prolonged sedation Phlebitis 0.03–0.1 mg/kg q 0.5–6 hr Useful in acute agitation Alpha hydroxy midazolam Not useful in acute agitational states Difficult to titrate continuous infusions Polyethylene glycol Propylene glycol ATN Lactic acidosis
    25. 25. Benzodiazepines- side effects Dose dependent CNS suppression Dose dependent centrally mediated respiratory depression Cardiovascular minimal depression
    26. 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. 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. 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. 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. 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. 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. 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. 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. 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. 35. Adverse Effects of Haloperidol QT prolongation leading to ventricular dysrhythmias, including torsades de pointes Extrapyramidal symptoms Neuroleptic malignant syndrome
    36. 36. Monitoring Crit Care 2002, 8:290–298 ©2002 Adequate
    37. 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. 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. 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. 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. 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
    42. 42. Neuromuscular Blockade in ICU
    43. 43. Indications Facilitate intubation Facilitate mechanical ventilation Control of ICP Control muscle spasms Decrease oxygen consumption
    44. 44. Neuromuscular Agents Depolarizing muscle relaxants Suxamethonium Non depolarizing muscle relaxants - Aminosteroidal Compounds Pancuronium, Pipecuronium, Vecuronium, Rocuronium - Benzylisoquinolinium Drugs Atracurium, Cis atracurium, Dxacurium
    45. 45. Pancuronium Long acting Vagolytic – causes increase in heart rate Active metabolite Prolonged effects in renal failure and cirrhosis Dosage – 0.06 – 0.1mg/KG
    46. 46. 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
    47. 47. Rocuronium Intermediate acting Very rapid onset of action Metabolite has only 5 -10% activity of parent compound Dose: 0.6 – 0.1 mg/kg
    48. 48. 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
    49. 49. 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
    50. 50. Complications Prolonged recovery from NMBAs Acute quadriplegic myopathy syndrome (AQMS)
    51. 51. 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
    52. 52. 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
    53. 53. 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
    54. 54. 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
    55. 55. 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
    56. 56. 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
    57. 57. 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
    58. 58. Thank You

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