Anesthesia 3rd Stage Lecture Notes PDF

Anesthesia 3rd stage Ministry of Higher Education and Scientific Research College of Health and Medical Technology Anaesthesia Techniques Department Teaching package for anaesthesia techniques Subject: anesthesi...

Anesthesia 3rd stage Ministry of Higher Education and Scientific Research College of Health and Medical Technology Anaesthesia Techniques Department Teaching package for anaesthesia techniques Subject: anesthesia techniques, 3rd stage. 2023-2024 Page 1 of 104 Anesthesia 3rd stage LECTURE ONE (1) Preoperative assessment and premedication The pre-operative assessment is an opportunity to identify co-morbidities that may lead to patient complications due to anesthesia or surgical procedure, during the operative or post-operative periods. Patients scheduled for elective procedures will generally attend a pre-operative assessment 2-4 weeks before the date of their surgery. Premedication is using of medications in order to prepare the patient for anesthesia and to help provide optimal conditions for surgery. Specific needs will depend on the individual patient and procedure. Goals of preoperative assessment: 1) Doctor-patient relationship 2) Plan of Anesthetic Technique 3) Screen for and manage co-morbid disease. 4) To assess and minimize risks of anesthesia. 5) To identify need for specialized techniques. 6) To identify need for advanced post-op care. 7) Preoperative Preparation. 8) Perioperative risk determination. 9) Reduce patient anxiety. 10) To obtain informed consent. Page 2 of 104 Anesthesia 3rd stage Minimum preoperative visit components (according to ASA): 1) Medical, anesthesia and medication history. 2) Appropriate physical examination. 3) Review of diagnostic data (ECG, labs, x-rays). 4) Assessment of ASA physical status. 5) Formulation and discussion of anesthesia plan. Note// ASA = American Society for Anesthesiologists. The ASA physical classification: ASA1: normal healthy patient. ASA2: Mild systemic disease - no impact on daily life. ASA3: Severe systemic disease - significant impact on daily life. ASA4: Severe systemic disease that is a constant threat to life. ASA5: Moribund, not expected to survive without the operation. ASA6: Declared brain-dead patient - organ donor. E: Emergency surgery. Page 3 of 104 Anesthesia 3rd stage History 1) Medical problems (current & past).  DM, HTN,COPD,CAD,thyroid disorder..  Regular medications  Previous surgeries; date:  5.Family anesthesia history:  Problems with anesthesia in family  type of anesthesia:  (Pseudocholinesterase deficiency and malignant hyperpyrexia) Page 4 of 104 Anesthesia 3rd stage 2) Previous anesthesia & related problems.  Allergy to drugs  PONV  Anesthesia awareness  Difficult intubation  Delayed emergence 3) Allergies and drug intolerances. 4) Medications, alcohol & tobacco. 5) Review of systems (include snoring and fatigue). 6) Exercise tolerance and physical activity level. Physical examination 1) Airway. 2) Heart and lungs. 3) Vital signs including O2 saturation (  Blood pressure, Resting pulse, rate, rhythm,  Respiration, rate, depth, and pattern at rest,  Body temperature 4) Height and weight (BMI). 5) Other Specific examinations depending on the individual patient and procedure. Page 5 of 104 Anesthesia 3rd stage Airway Assessment Predictors of difficult intubation Mallampati classification ULBT (upper lip bite test) Inter-incisors gap (IID) Thyromental distance (TMD) Forward movement of mandible Document loose or chipped teeth Tracheal deviation Movement of the Neck Modified Mallampati score: Used to predict the ease of endotracheal intubation, the score is assessed by asking the patient, in a sitting posture, to open his or her mouth and to protrude the tongue as much as possible. Page 6 of 104 Anesthesia 3rd stage  Class I: Soft palate, uvula, fauces, pillars visible.  Class II: Soft palate, major part of uvula, fauces visible.  Class III: Soft palate, base of uvula visible.  Class IV: Only hard palate visible. A high Mallampati score (class 3 or 4) is associated with more difficult intubation as well as a higher incidence of sleep apnea. Thyromental distance (TMD) Distance from the thyroid cartilage to the mental prominence when the neck is extended fully. Should be 7 cm Sternomental distance (SMD) Distance from the upper border of the manubrium sterni to the tip of the chin, with the mouth closed and the head fully extended. Should be > 12.5 cm Page 7 of 104 Anesthesia 2 – 3rd stage Laryngoscopy: Cormack and Lehane Also Look for: Body: obese? If female: large pendulous breast? Neck anatomy: short? thick? webbed? Mouth: limitations (opening)? Teeth? (number & health) Enlarged tongue? (hypothyroidism, acromegaly & obesity) Mandible (+TMJ): micrognathia,receding mandible (ask patient to sublux their lower incisor beyond upper incisor) Maxilla: protruding? (buck teeth) | Face: beard? Facial trauma? | Nose: nasal passage patency, Head size: Children (ex. hydrocephalus or rickets) | Adults (ex. acromegaly) Page 8 of 104 Anesthesia 2 – 3rd stage Cardiovascular system: Dysrhythmias Atrial fibrillation Heart failure Heart murmur Valvular heart disease Blood pressure is best measured at the end of the examination Respiratory system cyanosis pattern of ventilation respiratory rate RR Dyspnoea Wheeziness signs of collapse consolidation and effusion Page 9 of 104 Anesthesia 2 – 3rd stage Pulmonary disease Smoking Increased carboxyhemoglobin levels. Decrease ciliary function. Increase sputum production. Nicotine adverse effects on cardiovascular system. Preoperative advices:  2 days cessation can decreases nicotinic effect, improve mucus clearance and decrease carboxyhemoglobin levels  4-8 weeks of cessation are believed to be needed for postoperative complication reduction Asthma Obtain information about irritating factors, severity and current disease status. Frequents use of bronchodilators, recurrent hospitalization and requirements for systemic steroids are all indicators of severe disease. Those who received more than a (burst and taper) of steroids in the previous 6 months should be considered for stress dose perioperatively. Respiratory Tract Infection Patients presenting on the day of surgery with symptoms and signs of a lower respiratory tract infection should be treated appropriately and postponed to such time that they are symptom free. Page 10 of 104 Anesthesia 2 – 3rd stage Viral upper respiratory tract infection can cause bronchial reactivity which may persist for 3-4 weeks. Unless surgery is urgent, such patients should be postponed for 4 weeks to minimize the risk of postoperative respiratory infection INVESTIGATIONS. CXR Basic Investigations ECG CBC: Hb,TC/DC, Serology Other (if needed) ABO Rh typing Echocardiography RBS TFT Urea, Creatinine, Na+ ,K+ HbA1c PT/INR BT/CT, aPTT Urine RME LFT PFT Page 11 of 104 Anesthesia 2 – 3rd stage Prolonged fasting should be avoided as this is associated with dehydration, increased postoperative nausea and vomiting, electrolyte imbalance and patient distress. Optimal fasting hours decreases volume and acidity of stomach contents and reduce aspiration and regurgitation risk. Premedication: Is the administration of medication before the induction of anesthesia. The patient should enter the operation room: Free of apprehension Sedated Arousable Cooperative and these characteristic can be achieved by the premedication drugs The goal of the premedication was to:  Relief anxiety  Sedation  Amnesia  Analgesia  Drying of the airways  Preventing the autonomic reflex response  Reduction in the gastric fluid volume and acidity  Antiemetic activity  Reduction of anesthesia requirement  Facilitate smooth induction of anesthesia Prophylaxis against allergic reaction Page 12 of 104 Anesthesia 2 – 3rd stage The pharmacological premedication should be given either before surgery for 1- 2 hours (can be taken with small amount of water orally ; less than 30 ml) or at night before the operation Anxiolytic: These drugs used to decrease the anxiety of the patients and make him sedative and calm with amnesia (unable to remember) They act predominantly on GABA receptors Minimum cardiac and respiratory depression Do not produce nausea and vomiting Lack the analgesic effect Cross the placenta and may cause neonatal depression The main drugs that used are the benzodiazepines ; diazepam , midazolam , lorazepam ,alprazolam. Analgesic: They are groups of drugs that produces pain relief , the main group that used in premedication is the opioid analgesics which contains morphine , pethidine and fentanyl Can be given parentally Produce sedation Control elevated blood pressure during endotracheal intubation Fentanyl is preferred due to its rapid onset and short duration of action Page 13 of 104 Anesthesia 2 – 3rd stage Fentanyl: Potent analgesic 100 times more than morphine Metabolized in the liver and excreted in the urine Produce respiratory depression so use in caution with COPD Cause less nausea and vomiting Can be reversed by naloxone Dose 1-5 microgram / kilogram i.v 3. Anti-autonomic: They contain either anticholinergic or beta1blocker The anticholinergic drugs that used in the premedication are ; atropine ,hyoscine and Glycopyrrolate. Atropine has vagal inhibition (tachycardia), CNS stimulation , Antisialagogues (decrease salivation). The dose of atropine is 0.3 – 0.4 mg iv Hyoscine had less vagal inhibition effect with more effect on salivation but produce sedation and amnesia so should be avoided in elderly Glycopyrrolate Has no central action, because it does not cross the blood brain barrier. Had longer duration and less tachycardia They produce dry mouth They produce mydriasis (dilation of eye pupil ) Atropine may cause central anticholinergic syndrome (restlessness, agitation, somnolence, convulsion ) and this can be reversed by physostigmine Page 14 of 104 Anesthesia 2 – 3rd stage 4. Antiemetic: They are drugs used to decrease the incidence of nausea and vomiting , the most commonly used are : Ondansetron and Metoclopramide (plasil) The most common used antiemetic drug Dose 0.15 to 0.3 mg /kg and last for 12 hour Used in emergency anesthesia Act centrally as dopaminergic antagonist on the vomiting center in the medulla Act peripherally by increasing the rate of gastric emptying and increasing in the gut peristalsis May produce oculogyric (extrapyramidal) side effect Chronic drug used by patients: Drugs to be continued till the day of operation: antihypertensives except ARBs & ACE inhibitors (stop 24-36 hrs. preoperatively) Diuretics cardiac medications (beta blockers.digoxin, calcium channel blockers) Antidepressants Anxiolytics Thyroid medications Steroids & Statins psychiatric medications, birth control pills, eye drops heart burn & reflux medications asthma medications Page 15 of 104 Anesthesia 2 – 3rd stage Medicines with special attention  aspirin :reversal of platelet inhibition within 3 days of stopping do not discontinue in patients with drug eluting coronary stents until 12months of dual antiplatelet therapy completed bare metal stents :continue for 1 month  Thienopyridines (clopidogrel (Plavix),ticlopidine) reversal of platelet inhibition in 7 days for clopidogrel ,14 days for Ticlopidine for cataract sx:no need to stop for stents,same as aspirin  Oral hypoglycemics: discontinue on day of sx  Diuretics: discontinue on day of sx except thiazides taken as antihypertensive  sildenafil: discontinue 24hrs before sx  COX 2 inhibitors: continue on day of sx unless surgeon is concerned about bone healing  NSAIDs: discontinue 48hrs before day of Sx  Warfarin: discontinue 4days before day of sx  Mono amine oxidase inhibitors: continue medication and adjust anaesthesia plan accordingly. Page 16 of 104 Anesthesia 2 – 3rd stage LECTURE TWO (2) General anesthesia Definition: is a reversible state of hypnosis, analgesia, amnesia, muscle relaxation with good physiological homeostasis. Components of general anesthesia: 1. Sedation and reduced anxiety 2. Lack of awareness and amnesia 3. Skeletal muscle relaxation 4. Suppression of undesirable reflexes 5. Analgesia Note: Because no single agent provides all desirable properties, several categories of drugs are combined to produce optimal anesthesia. STEPS of ANESTHESIA General anesthesia has three main strategies: 1- Induction 2- Maintenance 3- Recovery Induction General anesthesia in adults is normally induced with an IV agent like propofol, producing unconsciousness in 30 to 40 seconds. Additional inhalation and/or IV drugs may be given to produce the desired depth of anesthesia Maintenance After administering the anesthetic, vital signs and response to stimuli are monitored continuously to balance the amount of drug inhaled and/or infused with the depth of anesthesia. Maintenance is commonly provided with volatile anesthetics, which offer Page 17 of 104 Anesthesia 2 – 3rd stage good control over the depth of anesthesia. Opioids such as fentanyl are used for analgesia along with inhalation agents, because the latter are not good analgesics. Recovery Postoperatively, the anesthetic admixture is withdrawn, and the patient is monitored for return of consciousness. For most anesthetic agents, recovery is the reverse of induction. Stages of anesthesia The depth of anesthesia has four sequential stages characterized by increasing CNS depression as the anesthetic accumulates in the brain. Stage I: Analgesia: Loss of pain. (loss of eyelid reflex) Stage II: Excitement: The patient displays delirium and possibly combative behavior. Potentially dangerous responses can occur during this stage including vomiting, laryngospasm, HTN, tachycardia, and uncontrolled movement Stage III: Surgical anesthesia : There is gradual loss of muscle tone and reflexes as the CNS is further depressed. Regular respiration and relaxation of skeletal muscles with eventual loss of spontaneous movement occur. This is the ideal stage for surgery. Stage IV: Medullary paralysis (Overdose) Severe depression of the respiratory and vasomotor centers occurs, Onset of apnea, dilated and nonreactive pupils, and hypotension to complete circulatory failure. Ventilation and/or circulation must be supported to prevent death. Page 18 of 104 Anesthesia 2 – 3rd stage INDUCTION METHODS Most anaesthetic inductions are performed using intravenous or inhalational (‗gas‘) induction; each has advantages and disadvantages as below: Page 19 of 104 Anesthesia 2 – 3rd stage LECTURE THREE (3) Intravenous Anaesthesia General anaesthesia may be produced by many drugs which depress the CNS, including sedatives, tranquillizers and hypnotic agents. Only a few drugs are suitable for use routinely to produce anaesthesia after intravenous (i.v.) injection. Properties of Intravenous Anesthesia Developed later than inhalational anaesthesia. used commonly to induce anaesthesia induction is usually smoother and more rapid than most of the inhalational agents. preferred now because it is faster with less risk of excitement or laryngospasm may also be used for maintenance, either alone or in combination with nitrous oxide they may be administered as repeated bolus doses or by continuous i.v. infusion. Used for sedation during regional anaesthesia used for sedation in the intensive care unit (ICU) used for treatment of status epilepticus. Used as the sole drug for short procedures (deep sedation) From induction to wake up-bolus of IV induction drug On entering the blood stream, a percentage of the drug binds to the plasma proteins, with the rest remaining unbound or ‗free‘. The degree of protein binding will depend upon the physical characteristics of the drug. The drug is carried in the venous blood to the right side of the heart, through the pulmonary circulation, and via the left side of the heart into the systemic circulation. Page 20 of 104 Anesthesia 2 – 3rd stage The majority of the cardiac output (70%) passes to the brain, liver and kidney (often referred to as ‗vessel rich organs‘); thus a high proportion of the initial bolus is delivered to the cerebral circulation. The drug then passes along a concentration gradient from the blood into the brain.  The rate of this transfer is dependent on a number of factors:  Arterial concentration of the unbound free drug  Lipid solubility of the drug  Degree of ionization.  Unbound, lipid soluble, unionized molecules cross the blood brain barrier the quickest.  Once the drug has penetrated the CNS tissue, it exerts its effects. Like most anaesthetic drugs, the exact mode of action of the intravenous drugs is unknown. It is thought that each drug acts at a specific receptor – GABAA, NMDA and acetylcholine receptors.  Following the initial flooding of the CNS and other vessel rich tissues with non-ionized molecules, the drug starts to diffuse into other tissues that do not have such a rich blood supply. This secondary tissue uptake, predominantly by skeletal muscle, causes the plasma concentration to fall, allowing drug to diffuse out of the CNS down the resulting reverse concentration gradient. It is this initial redistribution of drug into other tissues that leads to the rapid wake up seen after a single dose of an induction drug.  Metabolism and plasma clearance have a much less important role following a single bolus, but are more important following infusions and repeat doses of a drug. Page 21 of 104 Anesthesia 2 – 3rd stage  The fat, with its poor blood supply (vessel poor tissues), makes little contribution to the early redistribution of free drug following a bolus. However, following repeat doses or infusions, equilibration with adipose tissue forms a drug reservoir, often leading to a delayed wake up. In state of reduced cardiac output In circumstances when cardiac output is reduced, for example after major blood loss, the body compensates by diverting an increased proportion of the cardiac output to the cerebral circulation. This preservation of cerebral blood flow in these situations is paramount. Thus a greater proportion of any given drug will enter the cerebral circulation. As a result, the dose of induction drug must always be reduced. Furthermore, as global cardiac output is reduced, the time taken for an induction drug to reach the brain and exert its effect is prolonged. The slow titration of a reduced dose of drug is the key to a safe induction in these patients. Properties of The Ideal Intravenous Anaesthetic Agent 1. Physical properties  Water soluble & stable in solution  Stable on exposure to light  Long shelf life  No pain on intravenous injection  Painful when injected into an artery  Non-irritant when injected subcutaneously  Low incidence of thrombophlebitis  Cheap Page 22 of 104 Anesthesia 2 – 3rd stage 2. Pharmacokinetic properties o Rapid onset in one arm-brain circulation time o Rapid redistribution to vessel rich tissue o Rapid clearance and metabolism o No active metabolites. Pharmacodynamics properties o High therapeutic ratio (ratio of toxic dose : minimally effective dose ) o Minimal cardiovascular and respiratory effects o No histamine release/hypersensitivity reactions o No emetic effects o No involuntary movements o No emergence nightmares o No hang over effect o No adrenocortical suppression o Safe to use in porphyria. BENZODIAZEPINES: The mechanism of action was on the GABAA receptor. Flumazenil is a specific benzodiazepine–receptor antagonist that effectively reverses most of the central nervous system effects of benzodiazepines Pharmacokinetics Absorption: Benzodiazepines are commonly administered orally, IM, and IV to provide sedation or, less commonly, to induce general anesthesia. Page 23 of 104 Anesthesia 2 – 3rd stage Diazepam (Valium) was well absorbed from the gastrointestinal tract. IM and IV injections of diazepam are painful while midazolam has no pain. Distribution: valium (diazepam) is lipid soluble and readily penetrates into the blood, Redistribution is fairly rapid for the benzodiazepines while midazolam is water soluble. Biotransformation: diazepam depends on the liver for biotransformation (metabolism) into water-soluble end products. The metabolites of diazepam are pharmacologically active. It has long elimination half-life for diazepam (30 h). Excretion The metabolites of benzodiazepine are excreted chiefly in the urine. Intestinal - hepatic circulation produces a secondary peak in diazepam. Effects on Organ Systems (pharmacodynamics) A. Cardiovascular The diazepam had minimal cardiovascular depressant effects, it decreases blood pressure and sometimes increase heart rate. B. Respiratory: diazepam depresses the respiratory system. apnea may occur after induction; even small intravenous doses of diazepam have resulted in respiratory arrest. C. Cerebral: diazepam reduces cerebral oxygen consumption, cerebral blood flow, and intracranial pressure. It prevents and controls seizures, produce amnesia, mild muscle-relaxation, anti-anxiety, and sedation BARBITURATES: Sodium thiopental (thiopentone) Barbiturates depress the reticular activating system (RAS) in the brainstem, which controls multiple vital functions. Their primary mechanism of action is believed to be through binding to (GABA) receptor. Barbiturates potentiate the action of GABA Thiopental‘s great lipid solubility and high nonionized fraction (60%) account for rapid brain uptake (within 30 s) Page 24 of 104 Anesthesia 2 – 3rd stage Pharmacokinetics Absorption: thiopental was frequently administered intravenously for induction of general anesthesia in adults and children (prior to the introduction of propofol). Rectal thiopental has been used for induction in children Distribution The duration of sleep doses of the thiopental is determined by redistribution, not by metabolism or elimination. Redistribution to the peripheral compartment specifically, the muscle group lowers plasma and brain concentration within 20–30 min. Patients typically lose consciousness within 30 s and awaken within 20 min. Induction dose of thiopental will depend on body weight and age. Reduced induction doses are required for elderly patients primarily due to slower redistribution. Sodium thiopental (thiopentone) Presentation: Supplied as a pale yellow powder. Vials commonly contain sodium thiopental with 6% sodium carbonate. Reconstituted with water to yields a 2.5% solution (25mg.ml-1) with a pH of 10.8. The alkaline solution is bacteriostatic and safe to keep for 48 hours, but make it incompatible with many basic drugs. Main action:  Hypnotic and anticonvulsant Pharmaceutical: A dose (3–6 mg kg-1) of thiopentone produces a smooth onset of hypnosis within 30 seconds of intravenous injection. Page 25 of 104 Anesthesia 2 – 3rd stage Recovery after a single dose is rapid due to redistribution and there is a low incidence of restlessness and nausea and vomiting. Thiopentone is 65-85% protein bound in plasma. Metabolism is slow and occurs in the liver. Excretion of metabolites occurs mainly in the urine. Repeated doses or infusions of thiopental leading to an accumulation of the active drug and delayed recovery. Biotransformation: thiopental is principally metabolized by the liver via hepatic oxidation to inactive water-soluble metabolites. Excretion: the metabolites are excreted by urine Effects on Organ Systems A. Cardiovascular: Intravenous bolus induction doses of barbiturates cause a decrease in blood pressure and an increase in heart rate. Patients with poorly controlled hypertension are particularly prone to wide swings in blood pressure during anesthesia induction. The cardiovascular effects of barbiturates depend on rate of administration, dose, volume status, baseline autonomic tone, and preexisting cardiovascular disease. B. Respiratory: thiopental causes: Depress respiratory center. Apnea may occur after induction dose. Tidal volume and respiratory rate are decreased Thiopental incompletely depress airway reflex responses to laryngoscopy and intubation (much less than propofol) and airway instrumentation may lead to bronchospasm (in asthmatic patients) or laryngospasm in lightly anesthetized patients. Bronchospasm may occur Page 26 of 104 Anesthesia 2 – 3rd stage Clinical use:  induction of anaesthesia  Treatment of status epilepticus  Brain protection from the effects of hypoxia after stroke and head injury. Effects on Organ Systems C. Cerebral: Thiopental decrease cerebral blood flow, cerebral blood volume, and intracranial pressure. It also decrease cerebral oxygen consumption Some patients relate a taste sensation of garlic, onions, or pizza Thiopental do not impair the perception of pain. In fact, they sometimes appear to lower the pain threshold (increase the pain sensation) It controls seizures. Other Thiopental may precipitate acute intermittent porphyria in susceptible individuals. Anaphylactic allergic reactions are rare.  In particular, the usual recommended dose may need to be considerably reduced in elderly, debilitated and hypovolemic patients. Chemical:  Ketamine is a derivative of phencyclidine Presentation:  Ketamine is prepared in a slightly acidic colourless solution (pH 3.5–5.5) containing 10,50 or 100mg.ml 1. Page 27 of 104 Anesthesia 2 – 3rd stage Main action: Dissociative anaesthesia. Pharmaceutical:  Ketamine is unique amongst induction drugs in that it can be administered IV, IM, orally, nasally, rectally, subcutaneously and the preservative free solution epidurally.  For induction of anaesthesia a dose of 1–2 mg.kg-1 can be given IV, or 3–5 mg.kg-1 IM. plasma levels are usually achieved within 10–15 min after intramuscular injection.  The onset of action is slower than other induction drugs  Ketamine is metabolized in the liver, and excreted in the urine. Ketamine has multiple effects throughout the central nervous system, Inhibition of reflexes in the spinal cord Excitation in selected areas of the brain. ketamine functionally ―dissociates‖ the brain from the awareness sensation. Clinically, this state of dissociative anesthesia may cause the patient to appear conscious (eg, eye opening, swallowing, muscle contracture) but unable to process or respond to sensory input. Ketamine has been demonstrated to be an N -methyl- d-aspartate (NMDA) receptor antagonist. Pharmacokinetics A. Absorption Ketamine has been administered orally, nasally, rectally, subcutaneously, and epidurally, but in usual clinical practice it is given intravenously or intramuscularly plasma levels are usually achieved within 10–15 min after intramuscular injection. Page 28 of 104 Anesthesia 2 – 3rd stage B. Distribution Ketamine is more lipid soluble and less protein bound than thiopental. So rapid brain uptake and subsequent redistribution was found in ketamine (the distribution half-life is 10–15 min). Awakening is due to redistribution from brain to peripheral compartments. C. Biotransformation Ketamine is metabolized in the liver to several metabolites, one of which (nor ketamine) retains anesthetic activity. D. Excretion: End products of ketamine are excreted renally. Effects on Organ Systems A. Cardiovascular ketamine increases arterial blood pressure, heart rate, and cardiac output. These cardiovascular effects are due to central stimulation of the sympathetic nervous system and inhibition of the reuptake of norepinephrine. Increases in pulmonary artery pressure and myocardial work. ketamine‘s indirect stimulatory effects on the heart may be beneficial to patients with acute shock. B. Respiratory Ventilatory drive is minimally affected by induction doses of ketamine It may produce apnea. Potent bronchodilator, making it a good induction agent for asthmatic patients Upper airway reflexes remain largely intact C. Cerebral Ketamine increases cerebral oxygen consumption cerebral blood flow, and intracranial pressure. Undesirable psychotomimetic side effects (eg, disturbing dreams and delirium)during Page 29 of 104 Anesthesia 2 – 3rd stage recovery It had analgesic effect Ketamine comes closest to being a ―complete‖ anesthetic as it induces analgesia, amnesia, and unconsciousness. D. Gastrointestinal: Postoperative nausea and vomiting are common. Increase in salivation (can be reduced by premedication with anti-muscarinic drug such as Glycopyrrolate or atropine) PROPOFOL  Propofol action is on GABA receptor.  Propofol actions are not reversed flumazenil  it is not water soluble but it is available for intravenous administration as an oil- in-water emulsion containing soybean oil, glycerol, and egg lecithin.  A history of egg allergy does not necessarily contraindicate the use of propofol because most egg allergies involve a reaction to egg white (egg albumin), whereas egg lecithin is extracted from egg yolk.  Intravenous bolus dose (1–2.5 mg kg-1) for induction of anesthesia.  It causes pain during injection that can be decreased by prior injection of lidocaine.  Propofol formulations can support the growth of bacteria, so sterile technique must be observed in preparation and handling and it should be administered within 6 h of opening of ampule  Postoperative nausea and vomiting appear to be extremely uncommon Page 30 of 104 Anesthesia 2 – 3rd stage Pharmacokinetics A. Absorption Propofol is available only for intravenous administration for the induction of general anesthesia and for moderate to deep sedation. B. Distribution Propofol has a rapid onset of action(approximately 30 seconds). Awakening from a single bolus dose is also rapid due to a very short rapid distribution half-life (2–8 min). Recovery from propofol is more rapid than recovery from thiopental and ketamine  Propofol should be titrated against the response of the patient until the clinical signs show the onset of anaesthesia. The best endpoint is loss of verbal contact with the patient C. Biotransformation It has extrahepatic metabolism. Conjugation in the liver results in inactive metabolites The pharmacokinetics of propofol do not appear to be affected by obesity, cirrhosis, or kidney failure. Use of propofol infusion for long-term sedation of children who are critically ill or young adult neurosurgical patients has been associated with sporadic cases of lipemia, metabolic acidosis, and death, the so-termed propofol infusion syndrome. D. Excretion: Propofol is excreted in the urine by the kidney Effects on Organ Systems A. Cardiovascular: the major cardiovascular effect of propofol is  decrease in arterial blood pressure (Propofol causes the most marked decrease in blood pressure of all the induction drugs.)  Decrease in cardiac contractility. Page 31 of 104 Anesthesia 2 – 3rd stage  Factors associated with propofol- induced hypotension include large doses, rapid injection, & old age.  Myocardial oxygen consumption and coronary blood flow usually decrease comparably B. Respiratory  Propofol is a profound respiratory depressant that usually causes apnea following an induction dose. it depresses the normal response to hypercarbia. It induced depression of upper airway reflexes exceeds that of thiopental, allowing intubation, endoscopy, or laryngeal mask placement in the absence of neuromuscular blockade.  Although propofol can cause histamine release, induction with propofol is accompanied by a lesser incidence of wheezing in both asthmatic and non-asthmatic patients compared with barbiturates or Etomidate. Effects on Organ Systems C. Cerebral Propofol decreases cerebral blood flow, cerebral blood volume and intracranial and intraocular pressure. propofol and thiopental probably provide a similar degree of cerebral protection. Unique to propofol are its antipruritic properties. Its antiemetic effects provide yet another reason for it to be a preferred drug for outpatient anesthesia. Propofol has anticonvulsant properties, has been used successfully to terminate status epilepticus, and may safely be administered to epileptic patients. Induction is occasionally accompanied by excitatory phenomena such as muscle twitching, spontaneous movement, opisthotonus, or hiccupping. Page 32 of 104 Anesthesia 2 – 3rd stage Tolerance does not develop after long-term propofol infusions. Propofol is often combined with remifentanil, or ketamine for TIVA. Etomidate Chemical:  Etomidate is an imidazole ester. Presentation:  It is usually presented as a lipid emulsion or as a clear solution containing propylene glycol at a concentration of 2mg.ml-1.the pH of aqueous solution is 8.1 Main action:  Hypnotic Pharmaceutical:  The standard induction dose is 0.3mg.kg-1  The recovery is rapid due to redistribution to muscle and fat.  It is rapidly metabolized by hepatic and plasma esterases  Excretion is predominantly urinary Clinical use:  induction of anaesthesia is an ultrashort-acting, non-barbiturate hypnotic intravenous anesthetic agent. Etomidate does not have any analgesic properties. It is administered only by intravenous route. Etomidate has a favorable hemodynamic profile on induction, with minimal blood pressure depression, making it ideal for shock trauma, hypovolemic patients, or patients with significant cardiovascular disease. Etomidate has been approved for use during induction. Pharmacokinetics: The onset of action: 30 to 60 seconds, Peak effect: 1 minute Page 33 of 104 Anesthesia 2 – 3rd stage Metabolism: Metabolism is primarily hepatic by ester hydrolysis to inactive metabolites. Excretion: 75% of the administered dose is excreted in the urine on the first day after injection. Another route of excretion is bile. Like most intravenous anesthetics, etomidate is highly protein-bound (77%). Thus, it can achieve a higher concentration in the brain in low albumin states since it will be less bound to albumin, and more free-drug would be available in the brain. Adverse Effects Transient inhibition of adrenal steroid synthesis is considered etomidate's most significant adverse effect. Etomidate is no longer administered by continuous infusion because of the risks of sustained suppression of endogenous cortisol and aldosterone production. The most common adverse reaction associated with etomidate use is transient intravenous pain on injection. The pain appears less frequent when larger, more proximal arm veins are used, or IV lidocaine is given before an etomidate bolus. Transient skeletal muscle movements or myoclonus were observed in about 32% of the patients. Postoperative nausea and vomiting with etomidate are comparable to the general frequency of PONV. The incidence of PONV was higher when etomidate was used for both induction and maintenance of anesthesia in short procedures such as dilation and curettage or when analgesia was insufficient Cardiovascular Effects  Etomidate has minimal effects on the cardiovascular system and is the major reason for choosing this drug as an induction agent.  Etomidate does not release histamine. However, etomidate by itself, even in large doses, produces relatively light anesthesia for laryngoscopy, and marked increases in Page 34 of 104 Anesthesia 2 – 3rd stage heart rate and blood pressure may be recorded when etomidate is solely used for induction. Respiratory Effects  Ventilation is not significantly affected. Induction doses do not result in apnea unless opioids have also been administered.  The most distinctive effect on the respiratory system is a slight rise in arterial carbon dioxide tension (PaCO2). Central Nervous System Effects  Etomidate decreases cerebral metabolic rate, cerebral blood flow, and intracranial pressure.  Because of minimal cardiovascular effects, cerebral perfusion pressure is well maintained.  Etomidate lacks analgesic properties Page 35 of 104 Anesthesia 2 – 3rd stage LECTURE FOUR (4) Inhalational Anaesthetic Agents Definition: An inhalational anesthetic is a chemical compound possessing general anesthetic properties that can be delivered via inhalation.  Inhalational Anesthesia refers to the delivery of anesthetics gases or vapors to the respiratory system to produce anesthesia.  The main use of inhalational was to maintain anesthesia, some of them can be used as induction  They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporizer and an anesthetic delivery system.  The famous demonstration of an ether anaesthetic by William Morton in 1846.  The dose of inhalational anesthetic was mentioned as MAC Classification 1. Gases Nitrous oxide and Xenon 2. Volatile agent A-fluorinated ethers (isoflurane, sevoflurane and desflurane) B-halogenated hydrocarbon (halothane) Page 36 of 104 Anesthesia 2 – 3rd stage The exact mechanism of action for inhaled anesthetics remains mostly unknown. they work within the central nervous system by augmenting signals to (GABA receptors) while depressing neurotransmission pathways of acetylcholine to muscarinic and nicotinic receptors The two main theories for inhalational anesthetic action focus on direct interaction with two components of the cell membrane.  Lipid theory (Meyer–Overton relationship):Meyer and Overton showed a close relationship between the lipid solubility of the inhalational agent and its potency of anaesthetic activity. They noticed that there was a straight line relationship between log minimum alveolar concentration (MAC; i.e. potency) and the lipid solubility; the more lipid soluble the agent (represented by a higher log oil/gas partition coefficient), the greater the potency.  Protein site of action theory: Throughout the CNS, there are many excitatory and inhibitory ligand-gated ion channels. There is increasing evidence that anaesthetic agents act by inhibiting excitatory (serotonergic, neuronal nicotinic and N-methyl-D- aspartate (NMDA)) channels and activating inhibitory channels (γ-aminobutyric acid A (GABAA) and glycine). The forward movement of inhalational agent is determined by a series of partial pressure gradients, beginning at the vaporizer of the anesthetic machine, continuing in the breathing circuit, the alveolar tree, blood, and then tissue. The principal objective of that movement is to achieve equal partial pressures on both sides of each single barrier. Page 37 of 104 Anesthesia 2 – 3rd stage The alveolar partial pressure governs the partial pressure of the anesthetic in all body tissues; they all will ultimately equal the alveolar partial pressure of the gas. After a short period of equilibration the alveolar partial pressure of the gas equals the brain partial pressure. So there was an uptake , ventilation and concentration that effect the induction rate and awaking time Partial pressure is the ratio of the amount of substance in one phase to the amount in another phase Recovery from anesthesia depends on lowering the concentration of anesthetic in brain tissue. Anesthetics can be eliminated by biotransformation, transcutaneous loss, or exhalation. Biotransformation usually accounts for a minimal increase in the rate of decline of alveolar partial pressure. Diffusion of anesthetic through the skin is insignificant. So The most important route for elimination of inhalation anesthetics is the alveolus. AGENTS IN COMMON CLINICAL USE In Western countries, it is customary to use one of the four modern volatile anaesthetic agents –isoflurane, desflurane, sevoflurane or halothane–vaporized in a mixture of nitrous oxide in oxygen or air and oxygen. The use of halothane has declined because of medicolegal pressure relating to the very rare occurrence of hepatotoxicity. The use of sevoflurane has increased rapidly, particularly in paediatric anaesthesia because of its superior quality as an inhalational induction agent. Page 38 of 104 Anesthesia 2 – 3rd stage Desflurane produces rapid recovery from anaesthesia, but it is very irritant to the airway and is therefore not used as an inhalational induction agent. Characteristic of IDEAL inhalational: Non-flammable, non-explosive at room temperature Stable in light. Liquid and vaporizable at room temperature Stable at room temperature, with a long shelf life Stable with soda lime, as well as plastics and metals Environmentally friendly - no ozone depletion Cheap and easy to manufacture Non toxic Rapid induction and rapid recovery Safe with no toxic side effect *There was no ideal inhalation till now Common Undesirable effects of the volatile agents 1.They all depress respiration 2.Reduce uterine tone 3.Trigger MH 4.All increase cerebral blood flow and ICP. Page 39 of 104 Anesthesia 2 – 3rd stage POTENCY The potency of an inhalational anaesthetic agent can be measured by its (Minimum Alveolar Concentration- MAC) MAC :- (Minimal alveolar concentration ) The minimum alveolar concentration (MAC) of an inhaled anesthetic is the One MAC is defined as: The minimum alveolar concentration of an inhaled anesthetic is the alveolar concentration that prevents movement in 50% of patients in response to a standardized stimulus (eg, surgical incision). e.g : Halothane MAC 0.75% ’The MAC is a useful measure because it mirrors brain partial pressure, allows comparisons of potency between the inhaled agents, The MAC values for different anesthetics are roughly additive. For example, a mixture of 0.5 MAC of nitrous oxide (53%) and 0.5 MAC of halothane (0.37%) produces the same likelihood that movement in response to surgical incision will be suppressed as 1.0 MAC of isoflurane (1.7%) or 1.0 MAC of any other single agent. Page 40 of 104 Anesthesia 2 – 3rd stage MAC is reduced by: Nitrous oxide Hypothyroid/myxedema Hypocapnia Hypothermia-decrease is roughly linear Hyponatraemia Increasing age Hypoxaemia Hypotension Anemia Pregnancy CNS depressant drugs Other drugs: lithium, lidocaine, magnesium, Acute alcohol abuse MAC is increased by: Hyperthermia Hypernatraemia Sympatho-adrenal stimulation Chronic alcohol abuse Chronic opioid abuse Increases in ambient pressure Hypercapnia Decreasing age Thyrotoxicosis Page 41 of 104 Anesthesia 2 – 3rd stage HINT: Sex, Weight and Duration of anesthesia does not affect MAC Nitrous oxide MAC105% , Halothane (Fluothane) 0.75% ,Isoflurane 1.2% ,Desflurane 6.0% ,Sevoflurane 2.0 % NITROUS OXIDE (N2O) N2O is a relatively insoluble agent with a low blood–gas partition coefficient And has a high MAC (105) and is widely used in combination with other inhaled anaesthetic agents or with O2 as entonox. Physical proprieties:  It is inorganic anesthetic gas Slightly sweet-smelling gas Non-flammable but supports combustion Breaking down to O2 and nitrogen at high temperatures. Supplied as a liquid/gas in French blue cylinders Ice often forms on the cylinder during use It is colorless and essentially odorless It is stored as a liquid in blue cylinders with a gauge pressure of 51bar at 20ºC. The gauge pressure does not give an indication of cylinder content until all the remaining N2O is in the gaseous phase. It is more diffusible than oxygen or nitrogen Page 42 of 104 Anesthesia 2 – 3rd stage Induction and recovery: Nitrous oxide is Fast onset and recovery; strongly analgesic but weakly anaesthetic. It is widely used in obstetric practice to relieve pain during childbirth and in minor surgical procedures. Useful analgesic for dental extraction Both induction and recovery from anaesthesia are extremely rapid. It's previously known as (laughing gas) It rapidly enters enclosed air-containing spaces more rapidly than oxygen or nitrogen can leave. These spaces include the cuff of an endotracheal tube, the bowel, pneumothorax ,the middle ear, nasal sinuses and the eye and air emboli, and nitrous oxide will increase their volume It may cause postoperative temporary hypoxia (diffusion hypoxia). Effects of N2O Respiratory · Non-irritant. Depresses respiration slightly. May cause diffusion hypoxia at the end of surgery. Cardiovascular · Mild direct myocardial depression which is offset by an increase in sympathetic activity via its central effects.(Little effect on heart rate and BP usually) Central nervous system · Increases cerebral metabolism, cerebral blood flow and ICP slightly. Page 43 of 104 Anesthesia 2 – 3rd stage Toxicity · It interferes with DNA synthesis even after relatively brief exposure. Others: Post operative nausea and vomiting Does not affect hepatic or renal function, nor uterine or skeletal muscle tone. Prolonged use may cause bone marrow depression, megaloblastic anaemia and peripheral neuropathy. Generally considered as being safe during pregnancy Xenon It Is a noble gas with an anaesthetic effect. Xenon is a nearly ideal anaesthetic agent. At a concentration of 70% mixed with 30% oxygen it induces general anaesthesia without side effects. It cannot be synthetized and is isolated from air, which contains 0.0000087% xenon. inert and odourless gas very fast onset and offset of anaesthesia (low blood:gas partition coefficient) Expensive It is not metabolized and is excreted unchanged via the lungs. It is non-toxic, not flammable, non-irritant to the airway. Xenon has analgesic properties Muscle relaxation at higher concentrations. minimal cardiovascular effects (small decrease in heart rate only) Page 44 of 104 Anesthesia 2 – 3rd stage minimal respiratory effects (slows respiratory rate slightly, but increase tidal volume to compensate). It does not cause malignant hyperthermia. HALOTHANE Halothane is a highly soluble agent with a high blood–gas partition coefficient and its MAC is (0.75) Physical Properties Colorless liquid, Pleasant smell Halothane is a halogenated alkane, Supplied in liquid form with thymol 0.01% Halothane is unstable when exposed to light so thymol preservative and amber- colored bottles retard spontaneous oxidative decomposition. it was nonflammable and non-explosive It corrodes certain metals and dissolves into rubber. Its use rapidly spread because of its greater potency, ease of use, non-irritability and non-inflammability Risks of arrhythmias and liver damage on repeated administration (halothane hepatitis) Halothane is the least expensive volatile anesthetic. Effects: Respiratory Depress Minute ventilation largely due to decreased tidal volume The normal response to hypoxia and hypercarbia are blunted. It has a sweet non-irritant odour and may be used for gaseous induction. Halothane also bronchodilator and is useful in asthmatic patients. Non-irritant. Pharyngeal, laryngeal and cough reflexes are abolished early Page 45 of 104 Anesthesia 2 – 3rd stage Respiratory depressant, with increased respiratory rate and reduced tidal volume. inhibition of secretions. Cardiovascular Myocardial depression and bradycardia. Hypotension is common. (reduce sys. Vascular resistance) Myocardial O2 demand decreases. Arrhythmias are common, e.g. Bradycardia, ectopic Sensitizes the myocardium to catecholamines, e.g. Endogenous or injected adrenaline. Central nervous system Smooth rapid induction, with rapid recovery. Anticonvulsant action. Increases cerebral blood flow but reduces intraocular pressure. Others Dose-dependent uterine relaxation. Nausea/vomiting is uncommon. May precipitate Malignant Hyperthermia. Up to 20% is metabolized in the liver. Repeat administration after recent use may result in hepatitis. Toxicity · Hepatic damage (halothane hepatitis) · Factors include: multiple exposures, obesity, middle age and female sex. · Mortality is around 50-75%. · Halothane should be avoided:  If it has been given in the previous 3 months  If there is a past history of adverse reaction to halothane  If there is preexisting liver disease. Page 46 of 104 Anesthesia 2 – 3rd stage Contraindications · Severe hypovolemia · Malignant hyperthermia · Intracranial hypertension · Halothane hepatitis Isoflurane Physical proprieties: Colorless liquid Pungent odor MAC 1.20 Non-flammable, non-corrosive. With no additive. Relatively insoluble and has a low blood– gas partition coefficient. Is widely used for maintenance of anaesthesia and treatment of severe asthma in patients requiring mechanical ventilation in ICU. Effects Central nervous system Smooth, rapid induction, but speed of uptake is limited by respiratory irritation. Recovery is slower than with sevoflurane and desflurane. Anticonvulsant properties Reduces Cerebral Metabolic Rate of O2. Increases cerebral blood flow and ICP. Page 47 of 104 Anesthesia 2 – 3rd stage Decreases intraocular pressure. Has poor analgesic properties. Respiratory Irritant; more likely to cause coughing and laryngospasm(gaseous induction is not recommended) Respiratory depressant(more than halothane), with increased rate and decreased tidal volume. Causes bronchodilation. Cardiovascular Reduce SVR. Myocardial depression is less than with halothane Vasodilatation and hypotension commonly occur Compensatory tachycardia is common Myocardial O2 demand decreases, but tachycardia may reduce myocardial O2 supply. It may cause (coronary steal) whereby normally responsive coronary arterioles are dilated and divert blood away from areas supplied by diseased and unresponsive vessels, resulting in ischaemia Other: Dose-dependent uterine relaxation. Nausea/vomiting is uncommon. Skeletal muscle relaxation May precipitate MH. Widely used in neurosurgery Page 48 of 104 Anesthesia 2 – 3rd stage Contraindications · Severe hypovolemia · Malignant hyperthermia · Intracranial hypertension It was originally used as an inhalational agent in Japan and is now widely used in the world, particularly in paediatric practice. Sevoflurane is relatively insoluble in blood and has a low blood–gas partition coefficient. Physical proprieties: Colorless liquid Pleasant smelling MAC is (2) Non-flammable, non-corrosive, stable at ambient temperatures Supplied in liquid form with no additive. Interacts with soda lime to produce compounds A Non-pungent, low solubility- excellent for inhalation induction muscle relaxation (enough for pediatrics intubation) potentiates NMBA. The degradation of sevoflurane by soda lime and baralyme is results in the formation of Compound A which may cause renal tubular necrosis Page 49 of 104 Anesthesia 2 – 3rd stage Respiratory Well-tolerated Minimal airway irritation. Respiratory depressant, with increased rate and decreased tidal volume. Causes bronchodilatation. Cardiovascular Heart rate and contractility are unchanged, but a fall in SVR leads to a reduction in blood pressure. Vasodilatation and hypotension may occur Myocardial O2 demand decreases. Arrhythmias uncommon Central nervous system Smooth, extremely rapid induction and recovery. Early postoperative analgesia may be required as emergence Is so rapid. Increases the risk of emergence agitation Anticonvulsant properties. Reduces cerebral metabolic rate of O2 Decreases intraocular pressure. Has poor analgesic properties Dose-dependent uterine relaxation. Nausea/vomiting occurs. Skeletal muscle relaxation Page 50 of 104 Anesthesia 2 – 3rd stage May precipitate MH. Tracheal intubation may be performed easily with spontaneous Respiration. Considered the agent of choice for inhalational induction in pediatrics because of its rapid and smooth induction characteristics. Has also been used for the difficult airway, including airway obstruction. Its low blood: gas partition coefficient results in fast onset and offset of action. These properties make it ideal for long procedures where rapid wake-up is important to assess the patient. Physical proprieties: Introduced in the UK in 1994 a colorless liquid with slightly pungent vapor boiling point: 23°C, MAC: 5%–7% in adults; 7.2%–10.7% in children non-flammable, non-corrosive supplied in liquid form with no additive may react with dry soda lime to produce carbon monoxide Desflurane uses specific electrically powered vaporizer (Tec 6) due to its low boiling point. Page 51 of 104 Anesthesia 2 – 3rd stage Effects Respiratory 1) Causes airway irritation; not recommended for induction of anesthesia because respiratory complications (e.g. laryngospasm, breath-holding, cough, apnea) are common and may be severe. 2) Respiratory depressant, with increased rate and decreased tidal volume. Cardiovascular 1) Vasodilatation and hypotension may occur, similar to isoflurane, may cause tachycardia and hypertension via sympathetic stimulation, especially if high concentrations are introduced rapidly. 2) Myocardial ischemia may occur if sympathetic stimulation is excessive, but has cardioprotective effects in patients undergoing cardiac surgery. 3) Arrhythmia as uncommon, as for isoflurane, little myocardial sensitization to catecholamines. 4) Renal and hepatic blood flow generally preserved. Effects Central nervous system 1) Rapid induction (although limited by its irritant properties) and recovery. 2) May increase cerebral blood flow, although the response of cerebral vessels to CO2 is preserved. 3) ICP may increase due to imbalance between the production and absorption of CSF. 4) Reduces CMRO2 as for isoflurane. 5) Has poor analgesic properties. Page 52 of 104 Anesthesia 2 – 3rd stage Others 0.02% of Desflurane undergoes metabolism by liver Dose-dependent uterine relaxation (although less than isoflurane and sevoflurane). Skeletal muscle relaxation; non-depolarising neuromuscular blockade may be potentiated Contraindications · Severe hypovolemia · Malignant hyperthermia · Intracranial hypertension Advantages and disadvantages of the modern volatile anaesthetic agents Page 53 of 104 Anesthesia 2 – 3rd stage Page 54 of 104 Anesthesia 2 – 3rd stage LECTURE FIVE (5) Pediatric Anesthesia It is often said that paediatric patients are ‗not simply small adults‘. The truth is that from the premature neonate to the near-adult adolescent, children are very diverse. Pediatric patients involve the fallowing age groups: - 1.Neonates (0–1 months). Up to 44 weeks post conception (includes premature neonates) 2.infants (1–12 months). From 44 weeks post conception – 1 year 3.toddlers (12–24 months). 4.young children (2–12 years of age). Pediatric anesthesia has differing anesthetic requirements. physiological, anatomic, and pharmacological characteristics of each group. Indeed, infants are at much greater risk of anesthetic morbidity and mortality than older children; risk is generally inversely proportional to age. Estimation of weight It is essential that every child is weighed prior to anaesthesia. This allows correct calculation of drug doses and selection of anaesthetic equipment. Weight can also be Page 55 of 104 Anesthesia 2 – 3rd stage estimated from the age of the child from standard growth charts, from the length of the child, or using this formula: Age of child Formula to estimate weight in kg 0-12 months (0.5 x age in months) +4 1-5 years (2x age in years) +8 6-12 years (3x age in years) +7 Anatomical & Physiological Differences 1-Respiratory System Differences The major anatomical differences affecting airway management in neonates and infants are: · Relatively large head and prominent occiput · Small mandible · Relatively large tongue · Short neck narrower nasal passages, an anterior and cephalad larynx, a longer epiglottis, and a shorter trachea. These anatomic features make neonates and young infants obligate nasal breathers until about 5 months of age · Soft tracheal cartilages, easily compressed. These differences predispose to airway obstruction, particularly if the child‘s head is placed on a pillow, or the soft tissues on the floor of the mouth are compressed, or the head is hyperextended. Ideally, maintain the child‘s head in a neutral position, or slightly extended. Page 56 of 104 Anesthesia 2 – 3rd stage Anatomical differences affecting the larynx include:  A high, anterior position of the larynx (level of C3-4 in infants compared to C5-6 in adults)  A long, U-shaped epiglottis  The narrowest part of the airway is at the cricoid cartilage (below the vocal cords). o The narrowest part of the airway in adults is at the vocal cords. o Adeno-tonsillar hypertrophy is common in children 3 – 8 years of age. o Airway obstruction may develop after induction of anaesthesia; an oropharyngeal may help to maintain a patent airway. o Take care when passing nasopharyngeal, nasotracheal and nasogastric tubes in these children. Children aged 5-13 years may have loose teeth; take note of loose teeth at your pre- assessment visit Page 57 of 104 Anesthesia 2 – 3rd stage The major physiological differences in respiratory system  Faster respiratory rate  Lower lung compliance  Greater chest wall compliance  Lower functional residual capacity  high metabolic rate and oxygen consumption Note: children tidal volume is relatively fixed (5-7 ml.kg-1), and the infant can only increase minute ventilation by increasing respiratory rate.  Apnoeas are particularly common in premature and ex-premature infants, so monitor all babies for apneas after surgery; until they are 60 weeks post conception. If a mechanical ventilator is used, select the appropriate tidal volume and respiratory rate for age – pressure control ventilation is preferred 2-Cardiovascular considerations  Residual fetal circulation  Noncompliant left ventricle : so increase in cardiac output is achieved through an increase in heart rate (Heart-rate-dependent cardiac output)  Faster heart rate: It is important to avoid bradycardia. This should be treated rapidly if it occur; the most common cause is hypoxia Lower blood pressure Page 58 of 104 Anesthesia 2 – 3rd stage  Activation of the parasympathetic nervous system by anesthetic overdose, or hypoxia can quickly trigger bradycardia and profound reductions in cardiac output.  Bradycardia that can lead to hypotension, asystole, and intraoperative death.  The immature heart is more sensitive to depression by volatile anesthetics and to opioid-induced bradycardia.  The main causes of neonatal bradycardia and cardiac arrest during anesthesia are: -  Respiratory causes: - airway obstruction, bronchospasm, inadequate O2 delivery.  Pharmacology causes: -inhalation agents, succinylcholine, anticholinesterase.  Metabolic causes: -hypothermia, anemia, hypoglycemia.  Children are more susceptible than adults to cardiac arrhythmias, hyperkalemia, masseter spasm, and malignant hyperthermia associated with succinylcholine.  When a child experiences cardiac arrest following administration of succinylcholine, immediate treatment for hyperkalemia should be instituted Page 59 of 104 Anesthesia 2 – 3rd stage 3. Metabolism & Temperature Regulation Differences. Neonates promote greater heat loss to the environment and liable to hypothermia Because: - 1. Thin skin. 2. Low fat content. 3. Greater surface area relative to weight. 4. Inadequately warmed operating rooms (cold theater) 5. Prolonged wound exposure. 6. Administration of room temperature intravenous or irrigation fluid. 7. Dry anesthetic gases 8. Effects of anesthetic agents on temperature regulation center. Even mild degrees of hypothermia can cause perioperative problems which including: - Delayed awakening from anesthesia. Cardiac irritability and arrest. Respiratory depression. Altered responses to anesthetics and Neuromuscular blockers, and other agents. 4-Renal & Gastrointestinal Function Differences  The total body water is about 80% of body weight at birth, gradually decreasing with age. fluid loss is more critical problem to them.  Immature kidney function increases the importance of meticulous attention to fluid administration in the early days of life  Neonates also have a relatively increased incidence of gastroesophageal reflux.  The immature liver conjugates drugs and other molecules less readily early in life. Page 60 of 104 Anesthesia 2 – 3rd stage 5-Glucose Homeostasis Differences  Neonates have relatively reduced glycogen stores, predisposing them to hypoglycemia. 6-Pharmacological Differences: The main difference is prolonging the clinical duration of action of drugs such as thiopental and fentanyl. this Because: - 1. larger pediatric intravascular and extracellular fluid compartments compare with adult. Neonates and infants have a proportionately greater total water content than adults (50–60%). 2.Immaturity of hepatic biotransformation pathways, 3.Decreased protein for drug binding. 4.Smaller muscle mass in neonates prolongs or delaying redistribution of some drugs such as thiopental and fentanyl. Volatile anaesthetic  Neonates are more sensitive to volatile agents than older children  The minimum alveolar concentration (MAC) values are decreased in neonates but increased in infants and children compared to adults. Sedatives and hypnotics Children are particularly sensitive to sedative and hypnotic drugs such as barbiturates and benzodiazepines due to the Immature hepatic biotransformation and Decreased protein binding so these drugs should be used with caution, in weight appropriate doses, titrated according to effect. Page 61 of 104 Anesthesia 2 – 3rd stage Muscle relaxants Neonates and infants are more sensitive to non-depolarizing neuromuscular blocking drugs because Immature neuromuscular junction. A normal loading dose is given but subsequent doses should be reduced Page 62 of 104 Anesthesia 2 – 3rd stage LECTURE SIX (6) Pediatric Anesthesia  Preoperative Preparation  All children should be visited preoperatively by the anaesthetist responsible for caring for them in the perioperative period.  There is an increased incidence of airway problems during anaesthesia  children are more at risk of laryngeal spasm, breath-holding and bronchospasm  in the postoperative period the chance of post-intubation croup is increased.  It is extremely important that the child is weighed before arrival in theatre, because body weight is the simplest and most reliable guide to drug dosage.  Veins suitable for insertion of a cannula should be identified.  Morbidity and mortality caused by aspiration of gastric contents are extremely rare in children undergoing elective surgery.  Prolonged periods of starvation in children, especially the very young infant, are harmful.  These children, who have a rapid turnover of fluids and a high metabolic rate, are at risk of developing hypoglycaemia and hypovolaemia.  Solids (including breast and formula milk) should not be given for at least 6 h before the anticipated start of induction. Page 63 of 104 Anesthesia 2 – 3rd stage  In the emergency setting, e.g. the child who has sustained trauma shortly after ingesting food, it is probably best (if possible) to wait 4 h before inducing anaesthesia. Clearly, in this situation risk–benefit judgements have to be made.  If it is surgically possible to wait 4 h, an i.v. infusion of a glucose-containing solution such as 5% dextrose with 0.9% NaCl, must be commenced and, if necessary, appropriate fluid resuscitation undertaken.  Intravenous Induction  The same induction sequence can be used as in adults: a rapid-acting barbiturate (eg, thiopental, 3 mg/kg in neonates, 5–6 mg/kg in infants and children) or propofol (2–3 mg/kg) followed by a non-depolarizing muscle relaxant (eg, rocuronium, cisatracurium, atracurium, mivacurium, or succinylcholine).  Atropine should be given intravenously prior to succinylcholine.  It is important that children are accompanied into the anaesthetic room by someone with whom they are familiar.  The appropriate monitoring should be applied as soon as possible after the start of anaesthesia.  When inhalational induction is planned, clear, scented plastic masks are much more acceptable to small children than the traditional Rendell–Baker rubber masks.  Clear masks allow respiration and the presence of vomitus to be observed.  An alternative to using a mask is cupping the hands over the face of the child while holding the T-piece, It is important to ensure that the flow of fresh gas is directed away from the child‘s eyes because anaesthetic gases may be irritant.  When using a face mask, it is important that the soft tissue behind the chin is not pushed backwards by the fingers, thereby obstructing the airway. The anaesthetist’s fingers should rest only on the mandible. Page 64 of 104 Anesthesia 2 – 3rd stage  Airway Management  The Jackson–Rees modification of the Ayre‘s T-piece is the breathing system used traditionally for children under 20 kg in weight.  It has been designed to be lightweight with a minimal apparatus dead space. The apparatus may be used for both spontaneous and controlled ventilation  The open-ended reservoir bag is used for manually controlled ventilation. This mode of ventilation is especially useful in the neonate and infant.  Laryngeal mask airway (LMA) should be used only when it is planned that the child is to breathe spontaneously during surgery. It follows that it is unwise to use the device when neuromuscular blocking drugs are used.  It is mandatory to intubate the trachea during artificial ventilation.  Neonates with a tracheal tube must undergo artificial ventilation in order to reduce the work of breathing.  Infants have a head which is large and a neck which is short relative to the size of the body. Instead of placing a pillow under the head, it is usually necessary to place a small pad or pillow under the torso.  Tracheal intubation For children over 1 year:  Appropriate tube internal diameter (ID) can be approximately estimated by the formula: age / 4 + 4. Page 65 of 104 Anesthesia 2 – 3rd stage  Appropriate tube length in cm. can be approximately estimated by the formula: age / 2 + 12 oral (+15 for nasal). In infants:  Appropriate tube ID sizes for preterm: 92% on 2 room air Pale or dusky Spo2 > 90% on 1 oxygen Cyanosis Spo2 < 90% on 0 oxygen Respiration Can breathe Breathes deeply 2 deeply and and cough coughs freely Shallow but Dyspneic, 1 adequate Shallow or exchange limited breathing Apnea or Apnea 0 obstruction Circulation Page 13 of 33 Anesthesia 2 – 3rd stage Blood pressure Blood pressure ± 2 within 20 20% of normal mmHg of normal blood pressure Blood pressure Blood pressure ± 1 within 20 - 50 20% to 50 of mmHg of normal normal blood pressure Blood pressure Blood pressure ± 0 within > 50 50% of normal mmHg of normal blood pressure Consciousness Awake, alert Fully awake 2 and oriented Arousable but Arousable on 1 readily calling drift back to sleep No responsive Not responsive 0 Page 14 of 33 Anesthesia 2 – 3rd stage Activity Move all Same 2 extremities Move two Same 1 extremities No movement Same 0 Page 15 of 33 Anesthesia 2 – 3rd stage LECTURE (26-27) CRISES DURING ANAESTHESIA Laryngospasm Perioperative laryngospasm is a life-threatening complication during the perioperative period with an incidence of 0.78-5% depending on the surgical type, patient age, pre- existing conditions and anesthetic technique. It is defined by a sustained closure of the vocal cords as a primitive protective airway reflex to prevent tracheobronchial aspiration after an offending stimulus. The prolongation of this initial beneficial reflex after the stimulus has ceased, results in inadequate ventilation due to airway obstruction. It occurs most frequently during intubation or extubation due to a superficial level of anesthesia. The diagnosis can only be made if the closed glottis and vocal cords are visualized which is not possible in the great majority of cases. So usually, it depends on the anesthesiologist‟s clinical judgement. Clinical signs include:  inspiratory stridor,  paradoxical respiratory movements,  suprasternal and supraclavicular retractions and  rapidly decreasing oxygen saturation. As the obstruction progresses to a complete airway obstruction, the chest movements may be excessive but there is no movement of the reservoir bag and no capnogram reading. Page 16 of 33 Anesthesia 2 – 3rd stage Desaturation is the most common manifestation. Other manifestations are  bradycardia (6%),  negative pressure pulmonary oedema (4%),  cardiac arrest (0.5%),  pulmonary aspiration (3%),  arrhythmias and death. It is important to exclude other differential diagnoses such as: bronchospasm, supraglottic obstruction, psychogenic cause in anxious patients, vocal cord palsy, tracheomalacia, hematoma, foreign body, laryngeal edema or tracheal collapse. PATHOPHYSIOLOGY Causes of laryngospasm may be mechanical, chemical or thermal occurring around the glottis. They trigger the afferent fibers of the internal branch of the superior laryngeal nerve. The receptors are distributed along the glottis with the majority found on the laryngeal surface of the epiglottis. PREVENTION In order to reduce the incidence of laryngospasm, propofol induction is the best approach as it reduces the laryngeal reflexes, particularly in children with history of asthma. It was proven that lidocaine 1-2mg.kg-1 iv can be a preventive and corrective drug 2 minutes before extubation. Topicalization of the vocal cords with this agent has also been proven to be effective to prevent laryngospasm during general anesthesia in Page 17 of 33 Anesthesia 2 – 3rd stage children. Magnesium sulfate 15mg.kg-1 iv before tracheal extubation has the ability to decrease airway reflexes and cough and may play a role in laryngospasm prevention. Another important measure is removing all secretions or blood until the larynx is completely cleared before extubation. MANAGEMENT The first step is to remove the laryngospasm stimulus, followed by a firm and vigorous mobilization of the jaw backwards with extension of neck and head, and apply CPAP with 100% oxygen via a face mask. Although airway devices can be a trigger for laryngospasm, a Guedel cannula of correct size may be helpful in providing CPAP. Propofol in a sub hypnotic dose of 0.25-0.8mg.kg-1 iv usually breaks the spasm. If it does not, the next step is administration of succinylcholine 0.1mg.kg-1 iv allowing preservation of spontaneous ventilation. It has a quick onset because its ED95 is 0.3mg.kg-1. Rocuronium also has an ED95 of 0.3 and will have as rapid an onset as succinylcholine and could be an option in patients who are not able to tolerate succinylcholine. Other drugs useful for treatment are alfentanil and meperidine, especially when the laryngospasm trigger was a painful stimulus. Doxapram 1.5mg.kg-1 can suppress laryngospasm by increasing respiratory depth. Nitroglycerin 4mcg.kg-1 has also been reported as effective but only acts on the Page 18 of 33 Anesthesia 2 – 3rd stage smooth muscle and not on the skeletal muscle of vocal cords. The application of gentle pressure in the thoracic midline at a rate of 20-25 compressions per minute can reverse the spasm. FOLLOW-UP These patients should be under observation for 2-3 hours in the recovery ward to confirm a clear airway and to exclude possible complications such as pulmonary aspiration and post-obstructive pulmonary oedema. This can be a particularly harmful consequence of marked negative intrathoracic pressures due to the airway obstruction and may require intubation, ventilation and management in an ICU. Page 19 of 33 Anesthesia 2 – 3rd stage Page 20 of 33 Anesthesia 2 – 3rd stage High spinal anesthesia High spinal anesthesia is a complication of central neuraxial techniques that include spinal and epidural anesthesia It is defined as a spread of local anesthetic affecting the spinal nerves above T4 The effects are of variable severity depending on the maximum level that is involved but can include cardiovascular and/or respiratory compromise In total spinal anesthesia, there is an intracranial spread of local anesthetic resulting in loss of consciousness Contributing factors Local anesthetic dose Positioning of patient Pre-existing epidural block Unrecognized Dural puncture and intrathecal injection Accidental subdural block Accidental intradural space Prevention Epidural analgesia/anesthesia: o Use low concentrations of local anesthetic for labor analgesia o Prior to top-up: ▪ Assess block (to guide top-up dosage) ▪ Aspirate the epidural catheter with a 2 mL syringe to rule out intrathecal or intravenous placement o Consider giving large volumes of local anesthetic in divided doses (clinical urgency may preclude this) Page 21 of 33 Anesthesia 2 – 3rd stage Spinal anesthesia: o Consider the level (and therefore local anesthetic dose) required for surgery o Patient position: block height can be manipulated for up to 30 min when using hyperbaric (“heavy”) anesthetics – if using head down position to establish the block, remember to remove it as soon as possible o Patient characteristics: consider dose reduction in short or morbidly obese patients o Technique: ▪ Consider the effects of the speed of injection ▪ Avoid excessive barbotage o If performing a spinal following an epidural, a dose reduction may be necessary depending on the existing level of block (reductions to 1-1.5 mL of local anesthetic have been suggested following a failed epidural top-up); there is no clear consensus on this Epidural and spinal anesthesia: o Don‟t inject during a contraction/cough/Valsalva maneuver as this can increase the cephalad spread of local anesthetic o The use of the Oxford wedge is recommended to prevent the cephalad spread of local anesthetic (and to optimize airway positioning in the event of requiring general anesthesia) Symptoms T1- Cardiac sympathetic Hypotension T4 fibers blocked Bradycardia Paresthesia or C6- Hands and arms numbness in C8 hands/arms Page 22 of 33 Anesthesia 2 – 3rd stage Weakness of hands/arms Shortness of breath (accessory respiratory muscles affected) Shoulder weakness – respiratory compromise C3- Diaphragm and shoulders imminent 5 Hypoventilation and/or desaturation Respiratory arrest Intra Slurred speech cran Sedation ial Brain stem Loss of spre consciousness ad Page 23 of 33 Anesthesia 2 – 3rd stage Page 24 of 33 Anesthesia 2 – 3rd stage Local anesthetics toxicity Local anesthetics are commonly used in most medical and dental practices. While adverse effects are rare, the rising prevalence of local anesthetics in practice has resulted in a greater incidence of local anesthetic toxicity. From minor symptoms to major cardiac or central nervous system (CNS) effects, local anesthetic systemic toxicity (LAST) is an important consequence of which to be aware. Systemic toxicity was originally associated with seizures and respiratory failure. However, in the 1970s, cardiac effects were also recognized, as bupivacaine-associated fatal cardiac toxicity was discovered in healthy adults. Accidental intravascular injection during the administration of local anesthetics has long been recognized as the most common cause of LAST. However, certain co- morbidities can also increase the risk of local anesthetic overdose, and in turn systemic toxicity. These include hepatic dysfunction, cardiac disease, pregnancy, and metabolic syndromes. Additionally, patients at the extremes of age are at greater risk of toxicity, due to reduced clearance of the anesthetics. Specifically, infants (younger than 4 months old) have low a-acid glycoprotein plasma concentrations, which can result in lower intrinsic clearance of bupivacaine. Early recognition of CNS and cardiac toxicity in LAST can drastically change the clinical course. Following a single local anesthetic injection, LAST presented within 50 seconds in 50% of cases studied, and within 5 minutes in 75% of cases. If potentially toxic doses are administered, then it is recommended that patients be observed for at least 30 minutes. Page 25 of 33 Anesthesia 2 – 3rd stage Signs and symptoms LAST most commonly presents with CNS changes. Initial signs and symptoms include agitation, confusion, dizziness, drowsiness, dysphoria, auditory changes, tinnitus, perioral numbness, metallic taste, and dysarthria. Without adequate recognition and treatment, these signs as symptoms can progress to seizures, respiratory arrest, and/or coma. While CNS toxicity often presents with the above initial features, the most common consequence is seizures. Additionally, in the setting of intravascular injection seizures can be the initial presentation. Historically, local anesthetic literature suggested that cardiac toxicity often presented after antecedent CNS toxicity. However, with more potent local anesthetics, cardiac toxicity has been found to arise concurrently with seizures or even precede them. Hypotension and bradycardia are often the first signs of cardiac toxicity. However, arrhythmias are responsible for most reported cases, with bradyarrhythmia's being the most common. Additional signs of cardiac toxicity include hypertension, dyspnea, pain, wide complex, ST segment changes, asystole, tachycardia, and ventricular ectopy/tachycardia/fibrillation. Management Initial management of LAST should be focused on airway management, circulatory support, and reduction of systemic side effects. Immediate ventilation and oxygenation to prevent hypoxia and acidosis can facilitate resuscitation and reduce the likelihood of progression to seizures or cardiovascular collapse. If seizures do occur, immediate administration of benzodiazepines is recommended, to prevent injury and acidosis. Propofol or thiopental can be used if benzodiazepines are unavailable. However, these agents may worsen any associated Page 26 of 33 Anesthesia 2 – 3rd stage hypotension or cardiac depression. If these medications are unable to control tonic- clonic seizure movements, small doses of succinylcholine should be intermittently administered to stop muscular activity, and further acidosis. Management of local anesthetic-induced cardiac arrest is focused on restoring cardiac output. This is done to re-establish tissue perfusion, and in turn, prevent and treat any underlying acidosis. Recent case studies support the use of lipid emulsion therapy as soon as prolonged seizure activity or local anesthetic-induced arrhythmias are suspected. Theories suggest that it improves cardiac conduction, contractility, and coronary perfusion by drawing the lipid-soluble local anesthetic out of the cardiac tissue. A bolus of 1.5 mL/kg of 20% lipid emulsion and subsequent infusion of 0.25 ml/kg per minute should be given. The infusion should be continued for 10 minutes after hemodynamic stability is attained. An additional bolus and an increase of the infusion rate to 0.5 mL/kg per minute can be administered if stability is not achieved. The maximum recommended dose for initial administration is approximately 10 mL/kg for 30 minutes. Page 27 of 33 Anesthesia 2 – 3rd stage LECTURE NINTEEN (28-30) Apgar Score and neonatal resuscitation The Apgar score was initially proposed as a means of rapidly assessing the status of newborns at 1 minute after birth and as a means of determining whether neonate required respiratory support. “Every baby born in a modern hospital in the world is looked at first through the eyes of Virginia Apgar.” The Apgar score includes five variables with a range of scores from 0 to 2 (for a maximum of 10 points): heart rate, respiratory effort, muscle tone, reflex irritability, and color. Currently, the score is applied at 1 and 5 minutes, but in some cases the evaluation continues for as long as 20 minutes if continued resuscitative efforts are required. Page 28 of 33 Anesthesia 2 – 3rd stage Initial assessment A rapid initial assessment should usually occur before the umbilical cord is clamped and cut: o Observe tone (and color). o Assess adequacy of breathing. o Count the heart rate. o Take appropriate action to keep the baby warm during these initial steps. o This rapid assessment serves to establish a baseline, identify the need for support and/or resuscitation and the appropriateness and duration of delaying umbilical cord clamping. o Frequent re-assessment of heart rate and breathing will guide whether further interventions are needed. Tactile stimulation Initial handling is an opportunity to stimulate the infant during assessment by: o drying the infant o gently stimulating the infant as you dry them (e.g., rub the soles of the feet or back). Avoid more aggressive methods of stimulation. Tone and color A very floppy infant is likely to need respiratory support. Color is a poor means of judging oxygenation as cyanosis can be difficult to recognize. Pallor might indicate shock or rarely hypovolemia – consider blood loss. Page 29 of 33 Anesthesia 2 – 3rd stage Breathing Is the infant breathing? - Note the rate, depth and symmetry, work/effort of breathing as: o adequate o inadequate/abnormal pattern - such as gasping or grunting o absent. Heart rate Determine the heart rate with a stethoscope and a sa