3. Intravenous Anesthetic Agents.pdf

INTRAVENOUS ANESTHETIC AGENTS Tümay UMUROĞLU  General Anesthesia ⬇⬇⬇ ⇣ State of sedation, analgesia, amnesia and FEZ muscle paralysis Induced, reversible and controlled loss of consciousness...

INTRAVENOUS ANESTHETIC AGENTS Tümay UMUROĞLU  General Anesthesia ⬇⬇⬇ ⇣ State of sedation, analgesia, amnesia and FEZ muscle paralysis Induced, reversible and controlled loss of consciousness Medically induced coma, not a normal sleep Necessary to perform surgical procedures with *No pain *No muscle and reflex activity *No stress response (either psychologic and metabolic) *No traumatic memories Components of General Anesthesia  Mechanism of action of general anesthesia ⇣ is not entirely clear Signals along the nerves responsible for transmitting stimuli are ı * interrupted EE * failed to be processed by the central nervous system after the administration of a general anesthetic Target organ is BRAIN Potentiation of the effect of the inhibitory neurotransmitter GABA at GABAA receptors is the most important mechanism of action for barbiturates, benzodiazepines, etomidate and propofol Inhibit transmission of excitatory neurotransmitters (eg.acetylcholine) BUT Enhance transmission of inhibitory neurotransmitters (eg.GABA)  Stages of Anesthesia Sınav sorusu olab l r Stage 1 - Analgesia or Disorientation: Induction stage mostdangerous stage Stage 2 - Excitement or Delirium: disinhibition, delirium, uncontrolled movements, loss of eyelash reflex, hypertension, and tachycardia Airway reflexes ⇢ intact and hypersensitive to stimulation z p Airway manipulation ⇢ should be avoided (including both the placement and removal of endotracheal tubes and suctioning maneuvers) entübasyon bustegadeyapılır Stage 3 – Surgical Anesthesia: Maintenance stage Ed This is the targeted anesthetic level (can be achieved using inhalational or continuous infusion of intravenous drugs) Stage 4 - Overdose: This stage occurs when too much anesthetic N agent is given ⇢ resulting in severe brain depression dangerous I (Without cardiovascular and respiratory support, this stage is lethal)  Phases of Anesthesia İdama 6 IV anesthetics (like propofol), are unique (In routine practice) In maintenance agents that induce anesthesia rapidly as they phase, quickly achieve high concentrations in CNS IV agents are generally used together Analgesics (pain relievers) are also given in the with inhalational agents induction phase  Types of General Anesthesia Inhalational Intravenous Sevoflurane Thiopenthal Desflurane Propofol Benzodiazepines Etomidate Ketamine Opioids  Intravenous anesthesia is a type of anesthesia in which veins are used to inject IV agents into the bloodstream (circulation) Iz NEVER USE ARTERIES ! Gangrene, which is death of tissues usually impacting the toes, fingers, and limbs Loss of limb Inadvertent (unvoluntary) injection of some IV anesthetic agents cause more damage than the others (eg. Thiopenthal)  IV anesthetics are used 1- to induce (start) and to maintain (continue) general anesthesia in the operating room (OR) 2- for sedation and anxiolysis preoperatively 3- for procedures outside the OR 4- for procedures in the Intensive Care Unit (ICU) Larger doses of IV anesthetic agents may result in undesirable hemodynamic and respiratory effects Ey A preferred technique requires multiple medications used in smaller doses, in order to minimize the adverse effects ⥋ BALANCED ANESTHESIA Differences between IV agents and Inhalational anesthetics IV AGENTS INHALATIONAL ANESTHETICS Special equipments Not necessary Necessary Onset of action Faster Slower Rate of recovery Faster Slower Outpatient use Extensive Less Used solely Yes No Tekbaşına kullanılmaz  Intravenously administered agents rapidly distribute to the vessel-rich areas (CNS, heart, and kidneys) Laf Termination of effect is determined primarily by the redistribution of the drug to the muscle groups and less well-perfused areas of the Rules for IV Anesthetics body (fat and bone) The pharmacokinetics (what the body does to the drug) for each patient vary depending on body composition, cardiac output, plasma e protein level, metabolism, and excretion a The variability between patients makes impossible the exact effect and requires careful titration according to each patients' response  Rapid and smooth onset and recovery Amnestic Hypnotic Minimal hemodynamic and Ideal IV respiratory effect anesthetic agent Nonpainful to veins and tissues Few interactions with other medications No allergic reactions  Classification Non-opioids Opioids (Hypnotics) Barbiturates Morphine Benzodiazepines Meperidine Fentanyl Propofol üç Ketamine Etomidate Başıbüyük Sufentanil Alfentanil Remifentanil en cok bu k s kullanılıyor tÜçları b lmel s n z  1. Dose-dependent central nervous system depression Low doses → Sedation High doses → Hypnosis LEI 2. No analgesic effect Basic Rules (except ketamine) (They have to be used in combination with For an analgesic agent during general anesthesia!) Hypnotics Opioids N20 (nitrous oxide – azot protoxide) üzere 3. Dose-dependent respiratory depression resulting in hypoventilation or apnea (except ketamine)  Hypnotics Barbiturates Commonly classified into different classes by how long they act in the body Long Medium Short Very short acting The short acting barbiturates are the ones commonly used in anesthesia induction Thiopenthal – (Pentothal Sodium) Prototypical drug  Hypnotics THIOPENTHAL Effects on systems system Cardiovascular Hypotension (in the presence of shock, sepsis) Tachycardia Respiratory system Apnea No inhibition on airway reflexes Laryngoscopy or intubation may lead to KAT ITIS laryngospasm or bronchospasm Yükün  Hypnotics THIOPENTHAL Cerebral system Cerebral blood flow ↓ Cerebral metabolic rate ↓ Intracranial pressure ↓ (In the treatment of increased ICP) Anticonvulsant effect (In the treatment of status epilepticus)  Hypnotics THIOPENTHAL Asthmatic and atopic patients (histamine release from mast cells)  Hypnotics THIOPENTHAL EXTRAVASATION Extensive tissue necrosis depending on concentration and total amount injected INTRA-ARTERIAL INJECTION ↓ Arterial spasm Gangrene and loss of the related extremity  Hypnotics Side Effects THIOPENTHAL Apnea Hypotension Allergic reactions Laryngospasm, bronchospasm EE Vein irritation Pain on injection (1-2%) Phylebitis and tissue necrosis (When it’s used in high concentrations)  Barbiturates Hypnotics Benzodiazepines Propofol Ketamine Etomidate Anxiolytic Amnestic Hypnotic (high doses) Sedative Antiepileptic Premedication  Hypnotics Benzodiazepines Diazepam (Valium) Lorazepam Midazolam (Dormicum)  Hypnotics MIDAZOLAM Most commonly used benzodiazepine in premedication Short onset of action No pain on injection (water-soluble) Fast recovery time Minimal effect on heart rate and blood pressure  Hypnotics t En öneml özell ğ _düğp fluş retrograde m dazolam MIDAZOLAM anterograde Le Anterograde amnesia (midazolam) before surgery to inhibit unpleasant memories Retrograde amnesia (Other drugs)  Barbiturates Hypnotics Benzodiazepines PROPOFOL Ketamine GABA receptor agonist Etomidate Used to induce and maintain general anesthesia and to sedate patients for certain medical procedures Administered by bolus dosing or infusion Short-acting Rapid onset Fast and smooth wake up  Hypnotics PROPOFOL 1% propofol 10% soybean oil 1.2% purified egg phospholipid (emulsifier) 2.25% of glycerol EFT A good candidate for microbial contamination (It must be administered as soon as it is prepared)  Hypnotics Side Effects PROPOFOL 1. Hypotension * arterial and venous vasodilation * baroreceptor inhibition (no reflex tachycardia) * mild decrease in myocardial contractility 1. Apnea (following induction) 1. Pain on injection (most frequent side effect, especially in small veins, relieved with lidocaine preinjection) 1. Euphoria, hallucinations and disinhibition  Barbiturates Hypnotics Benzodiazepines Propofol KETAMINE NMDA (N-methyl-D-Aspartate) receptor antagonist Etomidate Produces Füze "dissociative anesthesia" + unconsciousness (State in which the patient has analgesia, amnesia and is "dissociated" from external events) G der ve tholomus bağlantısını Open eyes with nystagmus kes yor Unresponsiveness to external stimuli * Potent analgesic BUT weak amnestic  Barbiturates Benzodiazepines Propofol KETAMINE Etomidate Ideal induction agent in patients with shock, significant hypovolemia and cardiac tamponade (increase in sympathetic outflow, resulting in tachycardia and cardiac output) Bronchodilator Preserves respiratory drive Increased cerebral blood flow and metabolic rate (increased ICP) Increased oral secretions Kafatravmalarında kontro nd ke Unpleasant psychomimetic reactions (must be used together with a benzodiazepine)  Barbiturates Hypnotics Benzodiazepines Propofol Non-barbiturate hypnotic acting at the level of RAS Ketamine ETOMIDATE Safer than barbiturates Minimal hemodynamic changes (minimal blood pressure and heart rate changes) Minimal respiratory depression ‘Ideal drug for the anesthesia induction of cardiac patients (congestive heart failure or a hemorrhagic shock) No histamine release  Hypnotics Side effects (ETOMIDATE) Pain on injection (prepared in propylene glycol) Myoclonus (chest wall rigidity) Seizures Transient adrenal gland suppression Postoperative nausea and vomiting Non-opioids Opioids (Hypnotics) Barbiturates Morphine Benzodiazepines Meperidine Fentanyl Propofol Sufentanil Ketamine Alfentanil Etomidate Remifentanil  Analgesia Cough Clinical Uses of Diarrhea Opioid Analgesics Acute Pulmonary Edema Balanced anesthesia Mainly used to provide ANALGESİA  Exert their pharmacological actions through μ-opioid receptor (named after Morphine) MOP δ-opioid receptor (named after the tissue it was first isolated from, vas Deferens) DOP κ-opioid receptor (named after the first ligand, Ketocyclazine) KOP  Opioids Location Within the central nervous system (midbrain and brain stem areas) and in the dorsal horn of the spinal cord + Peripheral sites (vas deferens, knee joint, gastrointestinal tract, heart and immune system) (Each receptor has its own opioid effect)  Most of available Activation of μ-opioid Activation of δ-, κ- opioid analgesics receptor opioid receptor Act at μ-opioid analgesia analgesia receptor euphoria dysphoria respiratory Psychotomimetic (κ) depression Affective behavior (δ) nausea, vomiting Not cause respiratory decreased depression or gastrointestinal decrease in GI motility motility tolerance Analgesia without μ- dependence opioid side effect  Opioids Dose related The notable (The more medication you give, effects of this class of the more effect you get) drugs: *Analgesia *Sedation *Respirator Sedation and respiratory y depression depression limit their use  Opioids Side Effects Chest wall rigidity Nausea and (reducing thoracic compliance and Seizures Vomiting interfering with ventilation) Constipation Bradycardia (in chronic use) (high doses- due to vagal stimulation) Except meperidine Histamine release (Itching around the nose) Urinary (evident with morphine and meperidine) retention  Opioids Morphine Agonist at μ-opioid receptor and κ-opioid receptor Metabolism (in the liver) to 1. morphine-3-glucuronide 2. morphine-6-glucuronide 3. normorphine (Very active metabolites) (Repeated doses may cause respiratory depression) t Peak analgesic effect is at 30 to 60 minutes (after parenteral administration) The duration of effect is 3-4 hours. Morphine stimulates CTZ (nausea, vomiting) Edinger Westphal nucleus of III nerve (miosis) Vagal center (bradycardia)  Opioids Remifentanil (Ultiva) Agonist at μ-opioid receptor Ultra-short acting 2L (used as an infusion) Nonspecific tissue and plasma esterases - metabolism Side effects Bradycardia Hypotension Nausea Shivering  Fentanyl 100 times more potent than morphine Few cardiovascular effects Little release histamine Because of high lipid solubility, it enters brain rapidly and produces peak analgesia in 5 min after IV injection The duration of action is short: 30-40 min  Opioids Opioid reversal Naloxone (pure μ-receptor antagonist) e Opioid overdose (it attaches to opioid receptors and reverses and blocks the effects of opioids) (This means that Naloxone can quickly restore normal breathing if the breathing has slowed or stopped because of an opioid overdose)