Transcript sedation and analgesia in the icu

Picture depicting Sir Humphrey Davy experimenting Nitrous oxide at the pneumatic institution
SOURCES OF PAIN IN THE ICU
• Recent Surgery
• Pre-existing Disease
• Monitoring Devices – ex. Central lines, Pulmonary Artery Catheters.
• Endotracheal tubes
• Drains , Urinary Catheters.
• Nursing Care – Suctioning, Dressing Changes.
• Immobilisation
CONSEQUENCES OF PAIN
• Sleep Deprivation
• Agitation
• Splinting
• Stress Response –
• Stimulation of Autonomic Nervous System and release of Humoral factors leads to tachycardia
and hypertension and increased myocardial oxygen consumption – myocardial ischemia or
Infarction.
• Hypercoagulability – altered humoral response leading to increased levels of factor VIII ,
fibrinogen, platelet activity and inhibition of fibrinolysis.
• Immunosuppression – with reduction in number & function of granulocytes & lymphocytes.
• Catabolism
• Psychological Disturbances – vivid nightmares, hallucinations and paranoid delusions.
PAIN ASSESSMENT
• Most Reliable and Valid Indicator for Pain assessment is patient’s response and
self report.
• Therefore patient should be awake if possible.
• Intensity –
• Verbal Rating Scores – patient self suggests intensity –
no pain/mild/moderate/severe/very severe/worst possible pain.
• Visual Analog Scales – depicting on a chart the intensity of pain.
• Numeric Rating Scales – scaled from 1-10 depending on the intensity.
BEHAVIOURAL PAIN SCALE
DELIRIUM AND AGITATION
Fluctuating Mental
Status
Inattention
Disorganized
Thinking
Altered level of
Consciousness
80 % of ICU patients have delirium – may or may not be accompanied by agitation
GOAL OF SEDATION
• Daily goal is – AROUSABLE AND COMFORTABLE SEDATION
• This approach facilitates reductions in ICU LOS and the Duration of Mechanical
Ventilation compared to traditional sedative strategies.
• The optimal level of sedation for most patients is – one which offers comfort while
allowing interaction with the environment.
• Sedation need to be protocolized and titrated to the goal :
Lighten Sedation to appropriate wakefulness daily.
Effect of this strategy on the outcomes :
1-7 day reduction in length of sedation and MV needs
50% reduction in tracheostomies
BENEFITS OF ADEQUATE SEDATION AND ANALGESIA
• Facilitates Mechanical Ventilation
• Creates Anxiolysis, Analgesia, Amnesia
• Decreases Oxygen Consumption
• Reduces Dyspnea
• Prevents Patient self- injury
• Induces Sleep
• Creates patient unawareness
• Improves long term psychiatric outcomes
• Permits delivery of efficient care
• Reduces Nursing stress while ensuring Nursing safety
• Increases family acceptance of ICU care
GUIDELINES - SCCM
• Depth and Quality of sedation should be routinely assessed in all ICU patients.
• RASS and SAS are most valid and reliable scales for assessing quality and depth of
sedation in ICU patients.
• Use objective measures of brain function to adjunctively monitor sedation in
patients receiving neuromuscular blocking agents.
• EEG monitoring to be used for Non-Convulsive Seizure activity in ICU patients at
risk for seizures, or to titrate electro suppressive medication to achieve burst
suppression in ICU patients with elevated intracranial pressures.
• Target the lightest possible level of sedation and/or use daily sedative interruption.
• Use sedation protocols and checklists to facilitate ICU sedation management.
• Suggest using Analgesia first – sedation for intubated and mechanically ventilated
ICU patients.
• Suggest using non-benzodiazepines (either Propofol or Dexmedetomidine) rather
than Benzodiazepines (Midazolam or Lorazepam) in mechanically ventilated adult
ICU patients.
SCORING SYSTEM
• Should be simple, easily performed, non invasive and easily reproducible.
• Depth and Quality of Sedation should be routinely assessed in all ICU patients.
• What is adequate sedation?
RASS : 0-3
RAMSAY : 3
SAS : 3-4
RICHMOND AGITATION SEDATION SCALE
RAMSAY SEDATION SCALE
• Awake
1 Anxious and/or agitated
2 Cooperative , oriented and tranquil
3 Responds to commands
• Asleep
4 Brisk response to light glabellar tap or loud auditory stimulus
5 Sluggish response to light glabellar tap or loud auditory stimulus
6 No response to light glabellar tap or loud auditory stimulus
SEDATION AGITATION SCALE
1
2
3
4
5
6
7
Unarousable
Very sedated
Sedated
Calm and Cooperative
Agitated
Very Agitated
Dangerous Agitation
MEASUREMENT OF BRAIN ACTIVITY
• Objective measurement of brain function in patients receiving NMBA along with
sedation.
• Bispectral Index / EEG / Evoked potentials.
BISPECTRAL INDEX
• A practical, processed EEG parameter that measures the direct effects of sedatives
on the brain
• 3 components : Patient state Index
Cerebral state Index
Narcotrend Index
BIS RANGE GUIDELINES
ADVANTAGES OF BIS
DISADVANTAGES OF BIS
• Objective sedation assessment to patient’s
• Prone to artefacts
• Electromyography activity interferes with BIS
response
• Optimizes clinical and economic outcomes
• Minimizes consequences of over and under
sedation
• Improves quality of sedation management
• Numerical scale correlates to sedation
endpoint.
measures of sedation
• Confounding factors influencing BIS scores
Hypoglycaemia , Sleep , Temperature , Age,
Drugs (Aminophylline, Epinephrine, Ketamine)
• Increase variability of BIS in critically ill
patients
• Cannot be relied upon in circulatory arrest or
hypothermia.
EEG MONITORING
• EEG monitoring to be used for Non-Convulsive Seizure activity in ICU patients at risk for seizures,
or to titrate electro suppressive medication to achieve burst suppression in ICU patients with
elevated intracranial pressures.
• Target the lightest possible level of
sedation and/or use daily sedative
interruption.
Daily interruption of sedation and analgesia :
• Allow better assessment of patient’s sedative needs
• Reduces drug bioaccumulation
• Reduces incidence of post-traumatic stress disorder
• Reduces complications of critical illness
• More ventilator free days and earlier ICU and hospital discharge…but at the
expense of a higher incidence of self- extubation.
SEDATION THERAPY
Use sedation protocols and checklists to facilitate ICU sedation management.
Suggest using Analgesia first – sedation for intubated and mechanically ventilated
ICU patients.
NON PHARMACOLOGICAL THERAPY
• Good Communication with regular reassurance from nursing staff
• Environmental control such as humidity, lighting, temperature and noise
• Explanation prior to procedures
• Management of thirst, hunger, constipation and full bladder
SEDATION AND ANALGESIA – PHARMACOLOGIC THERAPY
The pharmacologic agent should possess the following qualities:
• Both Sedative and Analgesic properties
• Anxiolytic , Amnestic and Anticonvulsant properties
• No prolonged effects on memory
• Minimal Cardiovascular side effects
• Controllable Respiratory side effects
• Rapid onset/offset of action
• No accumulation in renal/hepatic dysfunction
• Inactive metabolites
• Inexpensive
• No interactions with other ICU drugs
• No long term psychological effects
SEDATION / ANALGESIA OPTIONS
• Rule out reversible causes of discomfort and anxiety – Hypoxemia, Hypercarbia, toxic/drug side effects.
• Assess comorbidities of the patient.
• Keep in mind the potential side effects of the drug chosen.
• Target irreversible aetiologies of Pain and Agitation.
PHARMACOKINETIC CONSIDERATIONS
• Patient’s Fluid Volume Status
• Capillary Leak (Changing volume of distribution)
• Serum Protein Levels
• Renal and Hepatic Function
• Hepatic Blood Flow
• Competition of combinations of drugs for carrier molecules, metabolic and
excretory pathways.
CHOICE OF ANALGESIA
OPIOID ANALGESIA
• Natural chemical derivative of opium
• Act on opioid receptors (mu, kappa and sigma receptors) present in the central nervous
system and other body systems
• Effects – Analgesia, Sedation, Euphoria, Pupillary constriction, Respiratory depression,
Bradycardia, Nausea, Vomiting, Constipation, Urinary retention, Pruritis & Physical
Dependence
• Most commonly used drugs for pain relief in the ICU
• Given as intravenous bolus doses or infusions
• No amnestic effects like Benzodiazepines
CLASSIFICATION OF OPIOIDS
OPIOIDS
Morphine & its analogues
Semisynthetic & synthetic agents
Phenylpiperidine
derivatives –
pethidine, fentanyl
Methadone
Derivatives –
Methadone,
Dextropropoxy
phene
Benzomorphan
derivatives –
Pentazocine
Thebaine
DerivativesBuprenorphine
Morphine
Diamorphine
Codeine
(Hydrocodone)
COMMONLY USED IV OPIOIDS
FEATURES
MORPHINE
FENTANYL
HYDROCODONE
Onset of action
5-10 mins
1-2 mins
5-15 mins
Bolus Dosing
2-4 mg every 1-2 hrs
0.35-0.5 mcg/kg every
0.5-1 hr
0.2-0.6 mg every 1-2 hrs
Infusion Rate
2-30 mg/hr
0.7-10 mcg/kg/hr
0.5-3 mg /hr
Lipid Solubility
x
600x
0.2x
Active Metabolites
Yes
No
Yes
Histamine Release
Yes
No
No
Dose Adjustment for
Renal Failure
Decrease by 50%
None
None
SOME OTHER OPIOIDS
• REMIFENTANYL
Ultra short acting opioid given by continuous iv infusion
1.5mcg/kg loading dose f/b continuous infusion at 0.5-15 mcg/kg/hr
Analgesic effects are lost within 10 mins of stopping the infusion
Drug Metabolism is by non-specific esterases in the plasma – no dose adjustment in hepatic or renal
failure
Most advantageous in Traumatic Head Injury patients where frequent assessment of cerebral function
is required
Abrupt cessation can cause withdrawal – beneficial if combined with a longer acting opioid
• An Agonist on K –receptors
PENTAZOCINE
a weak antagonist at mu and delta receptors
• Used to relieve moderate pain
analgesia by activating receptors in the spinal cord
• Less euphoria compared to morphine
• Can be administered orally or parenterally
• Adverse Reactions –
Dysphoria – higher doses can cause Hallucinations , Nightmares, Tachycardia , Hypotension and
Dizziness
Tolerance and dependence on repeated use
• Combined with Phenergan to avoid side effects like nausea and vomiting and give a mild sedative effect
• Oral tablets have Naloxone combination to prevent crushing and iv abuse
TRAMADOL
• Acts via the mu receptor
• Also Inhibits uptake of Serotonin and Noradrenaline with presynaptic stimulation
of serotonin release
• Used for moderate to severe pain in the post-operative patient
• Dose – 50-100 mg (i.v. , oral or i.m.) 4 - 6 hourly up to a maximum of 600 mg/day
SIDE EFFECTS OF OPIOIDS
Vasodilatation
and
Hypotension
Respiratory
Depression
Depression of
Gut Motility
Confusion
THE ABSTINENCE SYNDROME
Withdrawal Symptoms that occur on sudden cessation/reduction of opioid medication.
• Irritability
• Tremors
• Aggression
• Fever
• Diaphoresis
• Piloerection
• Pupillary Dilatation
• Diarrhoea
• Insomnia
Treatment – Reinstitution of and then slow withdrawal of opioid or introduction of opioid in
combination with a BZD
NON OPIOID ANALGESIA – NSAIDS AND OTHERS
Dosing
KETOROLAC
IBUPROFEN
ACETAMINOPHEN
30 mg i.v. or i.m. every 6
hrs for up to 5 days
400-800 mg i.v. every 6 hrs
1 gram i.v. every 6 hrs
Reduce dosing by 50 % for
age>65yrs or body weight
<50kg.
Comment
Daily dose should not exceed 4
grams.
NSAID
Has anti-inflammatory and
antipyretic effects.
NSAID
Actions are similar to
ketorolac.
No anti-inflammatory effects
which is a major disadvantage n
critically ill patients..
Serious complications are
uncommon when
treatment is limited to less
than 5 days.
Serious complications are
uncommon when used for
short term pain relief.
Since it is not a NSAID , the side
effect profile for this group is safe
except for hepatotoxicity in high
doses.
Side effects of NSAIDS – Renal Dysfunction, GI Bleeding, Increased bleeding tendency due to platelet
inhibition.
NEUROPATHIC PAIN
• Pain attributed to Diabetic Neuropathy and other Chronic illnesses causing nerve root pain
• Recommended Drugs : Gabapentin – 600 mg every 8 hrs
( MOA: acts on postsynaptic voltage gated calcium channels – inhibition of calcium influx
& decrease in presynaptic excitatory neurotransmitter release)
Carbamazepine – 100 mg every 6 hrs
Pregabalin – same mechanism of action as gabapentin but
higher efficacy and faster onset of action.
CHOICE OF SEDATIVES
BENZODIAZEPINES
• Anxiolytic, Anticonvulsant, Amnesic, Hypnotic and provides some muscle
relaxation.
• Effects are mediated by depressing the excitability of the limbic system via
reversible binding at GABA receptor complex
• Minimal Cardiorespiratory depressant effect
• Common Drugs in this class are Diazepam, Midazolam and Lorazepam
• Patient related factors that affect BZD response – Age, Concurrent pathology,
Prior alcohol use, Concurrent therapy with other sedative use
• Higher Volume of Distribution and slower clearance in the elderly
MIDAZOLAM
LORAZEPAM
DIAZEPAM
LOADING DOSE
0.01-0.05 mg/kg
0.02-0.04 mg /kg
0.05-0.2 mg/kg
MAINTENANCE DOSE
0.02-0.1 mg/kg/hr
0.01-0.1 mg/kg/hr
Rarely used
ONSET
1-5 mins
5-20 mins
2-5 mins
DURATION
2-4 hrs
2-6 hrs
3-11 hrs
CARDIAC EFFECTS
Minimal
Minimal
Present
RESPIRATORY EFFECTS
Important Depressant Effect
Important Depressant Effect
Important Depressant Effect
ANALGESIA
None
None
None
AMNESIA
Potent
None
None
ACTIVE METABOLITES
Yes
No
Yes
SIDE EFFECTS
Low BP
Low BP/ Propylene glycol
toxicity & nephrotoxicity
Low BP, Phlebitis
PROPOFOL
• The mode of action of Propofol is via the GABA receptor
• Rapid onset of action – 1-2 mins
• Metabolised rapidly hepatically and extrahepatically
• Recovery is within 10 mins of discontinuation, can accumulate with prolonged use
• Ideally to be infused via a large or a central vein
• Prolonged infusions – increase Triglyceride and Cholesterol levels
• Theoretical maximum dose is 4 mg/kg/hr
• Bolus Dose – not recommended
• Infusions at 25 to 100 mcg/kg/hr
• Caution : PRIS – Propofol Related Infusion Syndrome
PROPOFOL – ADVERSE EFFECTS
• Hypotension
Dose related
Decreased SVR and Contractility (Cardiac output)
• Respiratory Depression
Apnea can occur with Bolus Dosing
• Synergistic Cardiovascular and Respiratory Depression with Opioids
• Vehicle (Soybean Emulsion)
Hypertriglyceridemia
Phlebitis
Infection
PROPOFOL RELATED INFUSION SYNDROME
• Adverse drug event associated with high doses(>4 mg/kg/hr or >67mcg/kg/min) and long term use
for >48 hrs
• Clinical Features
Cardiomyopathy with acute cardiac failure
Bradycardia
Myopathy with or without Rhabdomyolysis
Severe Metabolic Acidosis
Hyperkalemia
Renal Failure
Hepatic Dysfunction
• Inhibition of Free Fatty Acid entry into the mitochondria due to mitochondrial respiratory chain
inhibition by propool results in failure of fat metabolism.
• MANAGEMENT
Supportive treatments addressing the clinical manifestations
The propofol infusion should be discontinued immediately
Alternative Sedative agent should be started
Intravenous Crystalloid and colloid replacement and vasopressor or inotropic
support
Cardiac pacing for symptomatic bradycardia
Hemodialysis or continuous renal replacement therapy to treat acute renal failure
KETAMINE
• Acts at the N-Methyl-D-Aspartate (NMDA) receptor
• Prevents Nitric Oxide Synthase release
• In sub anaesthetic doses it acts as a sedative and analgesic
• Increases Blood pressure, Intracranial pressure and Heart rate
• Bronchodilator properties, sometimes used in severe asthma
• In the ICU used in conjunction with a narcotic (opioid or BZD)
• Dose : 5-30 mcg/kg/min
• ETOMIDATE
OTHERS
Can produce hypnosis with concentrations of 300-500 ng/ml
• BARBITURATES
Pentothal and Thiopentone have been used in the ICU in management of patients with
head injuries and raised intracranial pressures & in treatment of refractory status epilepticus.
They cause severe cardiovascular depression and accumulate during infusions leading to
prolonged recovery times
• VOLATILE AGENTS
Isoflurane used in concentrations of up to 0.6% for long term sedation with minimal
cardiorespiratory side effects and rapid awakening
Desflurane is an effective sedative with rapid onset of effects
• BUTYROPHENONES AND PHENOTHIAZINES
HALOPERIDOL –
Useful in patients with delirium to calm them
Dopamine receptor antagonist
Can be given oral, intramuscular and intravenous
Intravenous route is the most preferable – improved absorption, no pain during injection, less patient
anxiety and less EPS
Bolus dosing – 0.5 mg in elderly to maximum of 10 mg in severe agitation
30 min interval between the doses to gauge effect of previous dose
Combination with BZD can be used for rapid sedation – lowers total dose and hence less S/E (like
EPS)
Side Effects – EPS, Seizures, Neuroleptic Malignant Seizures, Tardive Dyskinesia, Hypotension, QT
prolongation (main S/E)
QUETIAPINE - treatment of delirium in patients of Parkinson’s Disease and Lewy Body Dementia
ALPHA 2 AGONISTS
•CLONIDINE
Synergistic with opioids and acts the spinal cord to inhibit nociceptive inputs, thus imparts analgesia
Contraindicated in hypovolemia and causes hypotension, bradycardia and dry mouth
Selectivity : alpha 2 : alpha 1 – 250:1
T ½ is 10 hrs
Is sometimes used as an antihypertensive
•DEXMEDETOMIDINE
Causes Anxiolysis, Amnesia, Analgesia
Sedation occurs without respiratory depression
Is also a sympatholytic
Molecular targets & Neural substrates : Locus ceruleus and natural sleep pathways
Smooth emergence & weaning from mechanical ventilation
Selectivity : alpha 2 : alpha 1 – 1620:1
94% protein bound
Eliminated by liver and kidney
Onset is 5-10 mins , Rapid Redistribution is 6 min & T ½ is 2 hrs
Only available in iv form
Dosing – 1 mcg/kg loading dose over 10 mins f/b 0.2-0.7 mcg/kg/hr infusion
Even after 12-24 hrs of infusion no risk of accumulation
REGIONAL ANALGESIA TECHNIQUES
• Nerve blocks for Thoracic and Abdominal wall – Intercostal Nerve Block ,
Paravertebral Block , Interpleural Analgesia and Transversus Abdominis Plexus
Block
• Peripheral Nerve blocks for upper and lower extremities
• Epidural analgesia – Long acting drugs – Ropivicaine and Bupivicaine
• Better side effect profile with excellent patient tolerance but minimally used in ICU
• Most useful in chronic pain syndromes – prevention and treatment.
THE ART OF SEDATION
• Under Sedation
Fighting the ventilator
V/Q mismatch
Accidental Extubation
Catheter Displacement
Cardiovascular stress & Ischemia
Anxiety , Awareness about procedures
Post – traumatic stress disorder
• Over Sedation
Tolerance, tachyphylaxis
Withdrawal Syndrome
Delirium
Prolonged Ventilation
Cardiovascular Depression
Sleep Disturbance
Inability to test neurological function
TITRATION OF SEDATIVE MEDICATIONS
• Identify the target symptom or behaviour
• Assess the severity
• Agree on the appropriate symptom level for that patient at that time
• Realize that changes will occur
• Titrate the drug level to the achieve desired effect
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YOU