SEDATIVES and

MYORELAXANT AGENTS
Prof. Dr. Berrin Işık
Dr. Aycan Özdemirkan
SEDATIVES
 Sedation
Hypnosis

General
Analgesia
anesthesia
Anesthesia
Regional Muscle
anesthesia relaxation
 Sedation

Sedation is the act of calming

by administration of a sedative
vPurpose:
vTo provide tolerance for unpleasant procedures by relieving
anxiety and discomfort
vTo provide little or no movement for uncooperative patients
during procedures
Levels of Sedation
 When do we use it?

• Therapeutic or diagnostic procedures

• In addition to procedures performed under local or regional anesthesia
• Radiotherapy
• Gamma Knife
• Radiodiagnostic (MRI, CT, US)
• Gastroenterological procedures (endoscopy, colonoscopy, …)
• Extracorporeal shock wave lithotripsy
• Dental procedures
• Electroconvulsive therapy
Which patients require sedation?
• Patients with phobia and severe anxiety
• Patients with hyperdynamic conditions such as severe hypertension
or pheochromocytoma
• Combative, violant and uncooperative patients
• Patients with psychiatric disorders
• Patients with mental disorders
• Patients who are unable to stay immobile
• Children or advanced age population
• Patients with involuntary movements
 Risks of sedation

• Minor risks
• Nausea/vomitting, involuntary movements, hypotension, tachycardia,
undesired level of sedation (too deep or too superficial)
• Major risks
• Hemodynamic instability, respiratory failure, respiratory/cardiac arrest,
brain damage, death
Prerequisites for safe sedation

• Legal authority to perform sedation

• Knowledge of basic and advanced life support
• Emergency drugs (atropine, adrenaline, antiarrhythmics,..)
• Presedation assessment
• Preprocedural fasting
• Monitoring devices, oxygen supply, suction, team
• Monitoring during recovery
The ideal sedative
• Short onset of action
• Predictable duration of action
• Easily titratable
• Broad therapeutic window
• Minimal side effects
• Minimal drug interactions
• Inexpensive
• No active metabolites
Işık B (Ed.), Anestezi Pratiğinde Sedasyon,
Akademisyen Kitabevi, 2019..
 SEDATIVES
Intravenous anesthetics
Benzodiazepines • Propofol
• Midazolam • Fospropofol
• Diazepam • Ketamine
• Lorazepam • Dexmedetomidine
• Etomidate
Opioids • Barbiturates
• Morphine Inhalational anesthetics
• Meperidin
• Sevoflurane
• Fentanyl
• Sufentanil Others
• Alfentanil • Melatonin
• Remifentanil • Chloral hydrate
• Antihistamines
Mechanisms of Action

•γ-aminobutyric acid (GABA) receptors

•Opioid receptors
•Glutamate receptors
•∝-2 receptors
Clinical effects
•Anxiolysis
•Sedation, hypnosis
•Amnesia (anterograde)
•Antiepileptic
•Analgesic
•Cardiovascular and respiratory system depression
Antagonists of some sedatives
• Flumazenil
• Competitive antagonist for benzodiazepines
• Not safe in respiratory depression
• Duration of action is shorter than benzodiazepines

• Naloxone
• Competitive antagonist for opioids (μ)
• Reversal of respiratory depression
• May cause acute withdrawal syndrome
Muscle Relaxants
 Why is muscle relaxation needed?

§ To facilitate assisted ventilation and tracheal intubation

§ To avoid muscle movements during surgery and provide
enough relaxation
§ To facilitate mechanical ventilation in intensive care units
§ Occasionally for bronchoscopy and electroconvulsive
therapy
 Neuromusculer blocking agents (NMBs);

§ Prevent the transmissions at the neuromuscular junction

§ Cause relaxation of diaphragm → It must be used by the experts !
§ Require preparations for airway management
§ Do not provide unconsciousness, amnesia, or analgesia
§ Require the use of sedative-hypnotics or amnestic drugs
Peripherally acting NMBs

• Depolarizing blockers
• Mimic the action of acetylcholine
• Agonists
• Succinylcholine
• Nondepolarizing blockers
• Interferes with the action of
acetylcholine
• Competitive blockers
 Succinylcholine
In cases requring rapid muscle
• Rapid onset of action (30-60sec) relaxation and airway management
• Short duration (<10min) • Patients with short fasting time
• Difficult airway
• Side effects
• Diabetes Mellitus
• Hyperkalemia
• Obesity
• Rhabdomyolysis
• Hiatal hernia
• Cardiac arrest
• Pregnancy
• Trauma
 Nondepolarizing NMBs

• Longer duration of action (>10min)

• Effects can be reversed by other drugs
• Rocuronium
• Vecuronium
• Atracurium
• Pancuronium
Monitorization – Train of four (TOF)
Reversal of neuromuscular blockade
• Succinylcholine
• Hydrolized by pseudocholinesterase
• Nondepolarizing NMBs
• Cholinesterase inhibitors – Acetylcholine ↑ at the junction
• Neostigmine
• Pyridostigmine
• Edrophonium
• Physostigmine
• Sugammadex
• Relaxant-binding agent
• Steroidal NMBs (rocuronium, vecuronium)
Dantrolene

• Treatment of malignant hyperthermia

• Exerts its effects on muscle tissue
• Binds to ryanodine receptor and inhibits Ca release
• Causes muscle relaxation
• Should always be available
Summary - Sedatives and NMBs

• Very commonly used in anesthesia

• Provides sedation/facilitates anesthesia and surgery
• Life threatening side effects
• Must be used by experts