APEX FINAL 1 WITH ACTUAL CORRECT EXAM , Exams of Nursing

Download APEX FINAL 1 WITH ACTUAL CORRECT EXAM and more Exams Nursing in PDF only on Docsity! APEX FINAL 1 WITH ACTUAL CORRECT EXAM QUESTIONS AND VERIFIED RATIONALES ANSWERS LATEST UPDATE 2024 ALREADY GRADED A+ 100% GUARANTEED PASS!! Order of blockade for epidural No autonomic differential blockade Sensory is 2-4 dermatomes higher than motor Major cause of apnea with neuraxial anesthesia (and what is usually not the cause) Usually the result of cerebral hypoperfusion, not phrenic nerve paralysis Cause of drowsiness with neuraxial anesthesia reduces sensory input to the Reticular Activating System (RAS), causing drowsiness. saddle block given at the lower end of the spinal column (sacrum) to block the perineal area, or hyperbaric solution in lumbar w/ sitting position maintained until block sets up. opioid moa inhibit pain transmission (afferent signals) in the substantia gelatinosa via the dorsal horn benefit to using opioids with LA creates a denser block Recommendations for block placement: Glycoprotein IIb/IIIa antagonists Abciximab: Hold 1-2 days Tirofiban, Eptifibatide: Hold 8h Recommendations for block placement: Cox inhibitors Proceed if pt has normal clotting mechanism and is not on any other blood thinners Recommendations for block placement: Thienopyridine inhibitors Clopidogrel: Hold 7 days Ticlopidine: Hold 14 days Recommendations for block placement/catheter removal: Unfractionated Heparin SQ: Proceed if pt has normal clotting mechanism and is not on any other blood thinners IV: Hold 2-4 hours b/f block, and 1h after block placement Hold 2-4h after removing catheter Recommendations for block placement/catheter removal: low molecular weight Heparin Enoxaparin, Dalteparin, Tinzaparin Before block placement: Prophylactic (Once daily): Hold 12h Therapeutic (twice daily): Hold 24h Before catheter removal: Hold 12h After catheter removal: Hold 2h After single shot block Prophylactic (Once daily): Hold 6-8h Therapeutic (twice daily): Hold 24h Recommendations for block placement/catheter removal: warfarin before block: Hold 5d Can remove catheter when INR < 1.5 Recommendations for block placement/catheter removal: thrombolytic agents TPA, streptokinase, alteplase, Urokinase Absolute contraindication to neuraxial anesthesia Recommendations for block placement/catheter removal: Herbal therapies Garlic, Ginkgo, Ginseng Proceed if pt is not on any other blood thinners Normal length of transient neurological symptoms (TNS) 1-7 days Most common LA to cause transient neurological symptoms (TNS) Lidocaine List the structures a needle passes through for an epidural block Skin -> subcutaneous tissue -> subcutaneous fat -> supraspinous ligament -> intraspinous ligament -> ligamentum flavum -> epidural space List the structures a needle passes through for a subarachnoid block Skin -> subcutaneous tissue -> subcutaneous fat -> supraspinous ligament -> intraspinous ligament -> ligamentum flavum -> epidural space -> dura mater -> subdural space -> arachnoid mater -> subarachnoid space Organism most likely to cause post-spinal bacterial meningitis? Streptococcus viridans Wernicke-Korsakoff syndrome loss of neurons in cerebellum brought on by thiamine deficiency Anesthetic considerations for acute intoxication -Less anesthesia is needed -Aspiration precautions -Surgical bleeding ↑(inhibits platelet aggregation) -The brain is less tolerant of hypoxia -↑circulating catecholamine, labile VS and exaggerated responses to drugs and stimuli s/s of cirhosis N/V: Metabolic alkalosis & hypokalemia Pulmonary vasodilation R to L shunt hypoxemia Splenomegaly, esophageal varices (↑back pressure) encephelopathy (↑nitrogen/ammonia) Hepato-renal syndrome 3 major complications of cirrhosis Variceal hemorrhage from portal hypertension Intractable fluid retention (ascites & hepatorenal syndrome) Hepatic encephalopathy or coma Cirrhosis etiology alcoholism (fatty infiltration) biliary obstruction (inflammation) chronic hepatitis (inflammation) right-sided heart failure (↑ hepatic vascular resistance) α₁-antitrypsin deficiency (genetic) Wilson's disease (genetic) hemochromatosis (iron overload) cirrhosis healthy hepatic tissue is replaced by fibrous tissue and nodules CV changes w/ liver dx -hyperdynamic circulation=↑CO, ↓SVR, ↑RAAS activation, ↓response to vasopressors, diastolic dysfxn, ↓blood viscousity, anemia -portal HTN=↑hepatic vascular reisistance -> ↑back flow (esophageal varisces, splenomegaly)-> arteriovenous shunting d/t extensive systemic collateral vessels -Ascites (↓oncotic pressure, ↓protein binding) -alcoholic cardiomyopathy -preop HF Hematologic changes w/ liver dx Anemia (Acceptable hematocrit: 30%) Thrombocytopenia (Acceptable PLT is 100,000) Leukopenia Coagulation disorders Preservation of hepatic arterial bld flow is critical: portal venous blood flow is reduced What causes thrombocytopenia in liver dx decreased platelet production and splenic consumption Renal changes w/ liver dx Renal hypoperfusion -> ↓GFR -> ↑RAAS -> dilutional hyponatremia Protein loss and low oncotic pressure -> Ascites & Edema correct hypovolemia and diurese = Consider albumin, mannitol, potassium sparing diuretics CNS changes w/ liver dx Encephalopathy = accumulation of toxins (Nitrogen compounds= ammonia) breaks down the blood brain barrier Increased levels of GABA ↑Cerebral uptake of benzos Pulmonary changes in liver dx Hepatopulmonary syndrome: pleural effusions & Pulmonary hypertension Acites pushes up on diaphgram ->mechanical ventilation decreased R-L shunting may cause hypoxemia High occurrence of COPD secondary to smoking Autonomic changes in liver dx ↑RAAS, ↑SNS output Phase 1 drug metabolism Functionalization reactions Oxidation Reduction Deamination Dealkylation methylation Sulfoxidation hydrolysis most anesthetics undergo phase 1 metabolism (midazolam, diazepam, codeine, phenobarbital) Anesthetics ↓ hepatic bld flow which slows metabolism of drugs Phase 2 drug metabolism Conjugation reactions Phase I product (substrate) conjugates with a second molecule to make it water soluble Leads to formation of covalent linkage b/w functional group and glucuronic acid, sulfate, glutathione, amino acid, or acetate (e.g.,morphine,acetaminophen) TIPS procedure Transjugular intrahepatic portal-systemic shunt, lowers portal pressure in portal HTN Bypasses portion of the hepatic circulation by shunting blood from the portal vein to the hepatic vein reduces back pressure on sphlanic organs and ↓ bleeding from varices & ↓ascites sig risk: hemhorrage Cather placed in R IJ and advanced via Inferior Vena Cava into the right hepatic vein Can have lg amounts of bld loss Avoid N2O TIPs fluid management Lg amounts of albumin crystalloid not advised LR exacerbates liver failure secondary to the breakdown of bicarbonate in the liver Sodium retention limits amounts of NS Mannitol to maintain urine output of at least 50 mL/hour (avoid Lasix) Complications to watch for include liver laceration, gallbladder perforation, oliguric renal failure (secondary to contrast dye) and stent embolization Indication for TIPS Used to treat portal hypertension usually caused by cirrhosis or as a temporary solution for hepatorenal syndrome Liver dx preop labs Albumin, CBC, coags, electrolytes, glucose, ALT & AST, AlkPhos, Blood type and screen, serum ammonia level, toxicology screen if suspected substance abuse Liver dx CV considerations hyperdynamic circulatory state drugs that relax the sphincter of oddi Glucagon Glycopyrrolate Atropine •Increased BUM comes from the failing liver being able to clear nitrogenous waste (this can lead to cerebral edema Anesthetic mgmt of cirrohsis -depressed response to inotropes and vasopressors -alcoholic cardiomyopathy -HF -Preserve hepatic blood flow (volatile anesthetics decrease hepatic bld flow) -Maintain normocapnia -Avoid peep altered pharmacokinetics/dynamics w/ liver dx Altered volume of distribution: Intravascular volume unpredictable, esp with ascites tx ↓ serum albumin ↑ gamma globulins Porto-systemic shunted blood bypasses liver Drugs highly extracted by liver esp affected ↑ sensitivity to sedative medications (decreased metabolism, increased duration, increased GABA, NMDA inhibition) Ascites Decreased renal perfusion Altered intrarenal hemodynamics Enhanced proximal and distal sodium reabsorption Often an impairment of free water clearance Liver dx risk factors for mortality High Child-Pughs core Presence of ascites Elevated serum creatinine Pre-op upper GI bleed High ASA rating Anesthetic concerns w/ liver dx Hypoglycemia Coagulopathies (Vitamin k factors) PLT sequestration and thrombocytopenia (Splenomegaly secondary to portal HTN) ↓ protein synthesis and protein oncotic pressure= third spacing-> ↑ vol of distribution, (must consider for medication dosing) Varices (careful w/ NG/OG) Pos Pressure ↓ venous return Liver dx med consideration -Iso has the least effect on hepatic bld flow -Fentanyl is the opioid of choice -Avoid morphine sphincter of Oddi spasm & histamine release) Portal HTN tx IV Vasopressin or somatostatin Vasopressin: splanchnic vasoconstrictor, constriction of mesenteric arterioles, reducing inflow to the portal venous system 0.1 -0.4 Units per minutes -can infuse nitro to avoid systemic HTN Octreotide (somatostatin analog) ↓ gut motility and venous return to portal circulation 50 mcg/ hour infusion Compression of varices: Triple lumen Sengstaken-Blakemore tube Direct Sclerotherapy: Inj of sclerosing agent directly into bleeding vessel and/ or adjacent tissue Causes of ↑ SNS outflow which produces hepatic arterial vasoconstriction -Hypotension -Hypovolemia -Hypoxia -Hypercarbia (hepatic vasoconstriction) -Light anesthesia Abdominal surgery: most profound etiologic factor that results in decreased hepatic flow Avoid w/ liver dx -Hypotension -Excessive sympathetic activation -High mean airway pressures during controlled ventilation (decreased venous outflow=HTN) Halothane hepatitis impairment is largely attributed to decreased systemic blood pressure, as well as halothane specifically will impair hepatic blood flow even further through the abolition of the vasoconstrictor response to hypercarbia Hepatocyte hypoperfusion, hypersensitive immune response Sevoflurane Metabolism Inorganic fluoride ion production Sphincter of Oddi spasm ↑biliary pressure narcotic induced Morphine> meperidine > butorphanol > nalbuphine Prefer synthetic narcotics FENTANYL Other causes: Surgical manipulation, cold irrigation, contrast dye immunosuppressive drugs General immunosuppressants: steroids Calcineurin inhibitors: Cyclosporine, Tacrolimus Antimetabolites: Imuran, Mycophenolate Inhibitors of TOR (Target of Rapamycin) Antilymphocyte Antibodies Polyclonal Antibodies Monoclonal Antibodies Liver txp intraop complications Hypothermia, Hyperkalemia, hypocalcemia, Oliguria, Hypotension, Hypertension, post reperfusion syndrome Expect massive amounts of blood loss keep UOP minimum of 0.5 mL/ kg/hour pancreatitis surgical procedures Surgical drainage of pseudocyst: Usually done after cyst matures (6 weeks) Open or CT-guided external drainage Spontaneous resolution of pseudocysts may be expected in 20% or more of patients who have undergone surgical drainage adenocarcinoma: pancreatic cx Biliary obstruction likely (jaundice) Insulinoma: Cancer of beta cells, Insulin-secreting tumor of the islets of Langerhans, Profound hypoglycemia Gastrinoma (Zollinger-EllisonSyndrome) hyper secretion of gastrin: excessive gastric acid secretion Diarrhea or steatorrhea typically a non-beta cell pancreatic tumor Surgical excision of the lesion is tx of choice in pt's w/out metastasis Whipple (Pancreaticoduodenectomy) Head of pancreas & duodenum, portion of jejunum, distal stomach, & distal section of common bile duct are removed; biliary system, pancreatic system, & GI tract reconstructed -Choleodochostomy: The establishment of a fistula into the common bile duct -Pancreaticogastrojejunostomy(Pancreatic gastrojejunostomy) Lipolysis: breakdown of triglycerides to FFA acids and glycerol -stimulated by enzyme hormone-sensitive lipase Catabolic hormones that oppose insulin GH Cortisol Epinephrine Glucagon (defend against hypoglycemia) Insulin favors fat storage. Inhibits the use of fat as an energy source by inhibition of glucagon release Glucagon biologic antagonist to insulin enhance hepatic glucose output and increase plasma glucose stimulates catabolic processes (fat metabolism, gluconeogenesis) Hyperglycemia ↓ glucagon release from αcells. Factors that stimulate insulin secretion Glucose, mannose, fructose (hyperglycemia) Amino acids, ↑FFA GI/digestive hormones Acetylcholine (parasympathetic stimulation) β-adrenergic stimulation Factors that reduce insulin secretion Hypoglycemia Somatostatin Glucagon, cortisol, growth hormone (GH) α-Adrenergic Stimulation Guidelines for diagnosis of DM FPG ≥ 126 mg/dL or, random glucose level > 200 mg/dL DM comorbidities Pancreatectomy Cystic fibrosis Severe pancreatitis endocrine conditions: Cushing syndrome, Glucagonoma, Pheochromocytoma, Acromegaly Steroid-induced diabetes Gestational diabetes Chronic DM complications Microvascular: Retinopathy, Neuropathy, Nephropathy Macrovascular: CAD, PVD, Cerebrovascular dx Infection, Cataracts, Stiff joint syndrome, Glaucoma, Poor wound healing Cardiac complications w/ DM Hypertension, CAD, Autonomic nervous system dysfunctions Ischemic heart disease: most common cause of perioperative mortality in the diabetic patient Autonomic Nervous system dysfunction in DM Aspiration Nausea and vomiting Abdominal distension Preoperative aspiration prophylaxis: H2-receptor blockers, gastroprokinetic agents, pre-induction antacids Intubation during GA FBG above 350 may warrant cancellation Autonomic neuropathy: Impaired respiratory response to hypoxia hypoglycemia causes Drugs: Insulin, Sulfonylureas, Beta-blockers, Toxins: Ethanol Severe liver disease Altered physiology associated w/ gastric bypass Sepsis Insulin-secreting tumor of the islets of Langerhans (an insulinoma) Hypoglycemia s/s (awake) Confusion Dizziness Headache Weakness Seizure Aberrant behavior Loss of consciousness Hypoglycemia s/s under anesthesia Tachycardia Diaphoresis Anxiety Tremors Piloerection Pupillary dilation vasoconstriction can cause irreversible brain damage DKA Glucose: > 250 mg/dl pH < 7.3 Serum Bicarbonate < 18 mmol/L Serum Osmolality + Ketonemia: ++ Mental obtundation: Present Hypovolemia: Present HHS Glucose: > 600 mg/dl pH > 7.3 Serum Bicarbonate >15 mmol/L Serum Osmolality ++ (>330 mOsm/L) Ketonemia: Normal or slight+ Mental obtundation: Present Hypovolemia: Present Acute pancreatitis causes Alcohol abuse Trauma to or near pancreas Ulcerative penetration from adjacent structures (i.e. duodenum) Infection Biliary tract disease Metabolic disorders (HLD, hypercalcemia) Drugs (corticosteroids, furosemide, estrogens, thiazide diuretics) Surgery (post operative pancreatitis) Mobilization of abdominal viscera Cardiopulmonary bypass Causes of pancreatic pain Obstruction and distention of pancreatic ducts Edema, with stretching of pancreatic capsule Edematous duodenal obstruction Biliary tract obstruction Inflammatory exudates, blood and enzymes in the retroperitoneum Chemical peritonitis Major enzymes: Trypsin, Enterokinase, Bile acids -Pretreat with Octreotide (somatostatin analog): 100 mcg SQ 2 -3 times daily -Somatostatin: suppress the release of tumor products Sphlanic nerves T3-T11 isoflurane Volatile agent of choice, has the least effect on heart and hepatic blood flow. LMA Contraindications •Risk of Aspiration: Full stomach, hiatal hernia, small bowel obstruction, GERD, delayed gastric emptying. •Obstruction at the level of or below the glottis (tracheal tumor) •Poor Lung compliance •High airway resistance Asthma is indication for LMA What to do in the case of aspiration with an LMA •Leave the LMA in place •Trendelenberg position •100% O2 via ambu •low fgf and low TV •Suction through LMA •Evaluate for presence of gastric contents in sxn'd material Combitube Supraglottic double lumen device placed blindly in hypopharynx. Occludes esophagus while ventilating larynx (tip is placed in the esophagus). Do not hold cricoid pressure when placing this device. If there is pathology below the glottis this device may not work. Contraindications: •Intact gag reflex •Prolonged use (ischemia) •Esophageal disease (Zenker's diverticulum) •Ingestion of caustic substances fiberoptic bronchoscopy contraindications Relative contraindications (no absolute contraindications) •Hypoxia (lack of time) •Secretions not relieved by sxn •Hemmorhage (unable to visualize) •Uncooperative pt •Local anesthetic allergy Trigeminal (Cranial Nerve V) Sensory: nose to anterior 2/3 of tongue V1 Opthamalic: Nares and anterior 1/3 of nasal septum V2 Maxillary: Turbinates and septum V3 Mandibular: Anterior 2/3 of tongue Motor: 0 Glossopharyngeal (Cranial Nerve IX) Sensory: soft palate to anterior epiglottis Soft palate Oropharynx Tonsils Posterior 1/3 of tongue Vallecula Anterior side of epiglottis (afferent gag reflex) Motor: 0 superior laryngeal nerve (SLN) Branch of the vagus nerve, branches at the level of the hyoid. Internal branch Sensory: posterior side of epiglottis. Laryngeal mucosa to the level of VC's. Motor: 0 External branch Sensory: 0 Motor: Cricothyroid muscle Unilateral injury causes no harm, bilateral injury causes hoarseness recurrent laryngeal nerve (RLN) Branch of the vagus nerve Sensory: Below the level of the vocal cords -the trachea Motor: All intrinsic muscle except the cricothyroid Location: Runs under the aortic arch, ascends the trachea to the larynx. L RLN injury (PDA ligation, left atrial enlargment). Bullard Laryngoscope Fiberoptic device for indirect laryngoscopy Useful for pt's w/ small mouth openings (Pierre Robin, Treacher Collins). Mouth must be able to open minimum of 6mm. Do not need axis alignment to use (cervical spine injuries) Disposable attachment for tall pt's. Must be retrieved from mouth. Summarize nerve injury outcomes for Vagus, Internal branch of superior laryngeal, External branch of superior laryngeal, and Recurrent laryngeal (Unilateral and Bilateral) Vagus Unilateral: Hoarseness, Bilateral: Aphonia Internal branch of superior laryngeal No effect - this nerve is sensory only External branch of superior laryngeal Unilateral: Minimal effects Bilateral: Hoarseness and voice fatigue Recurrent laryngeal Unilateral: Hoarseness - left is most common Bilateral: Stridor, dyspnea (acute injury). aphonia (chronic injury) What structures does the RLN wrap around on the right and left side Right: Subclavian artery Left: Aorta Cormack and Lehane score 1: Full view of glottis 2: Partial view of glottis 3: Epiglottis only 4: No epiglottis or glottis Eschmann Introducer Bougie Intubating Stylet Helps facilitate intubation of a very anterior glottis with a coude tip. Cormack and Lehane score of 3. Feeling the clicks of the tracheal rings confirms placement. If no clicks extend to carina for "hold up" sign. ie you will not meet resistance if you're in the esophagus. Bronchial Blocker Used with a single lumen ETT to ventilate a single lung. Transtracheal Jet Ventilation Contraindications Upper airway obstruction Laryngeal injury Trachea Begins at C6, ends at T4-5 2.5cm wide, 10-13cm long Sensory innervation: Vagus Blood supply: inferior thyroid a., superior thyroid a., Bronchial a., internal thoracic a. Bronchi Mainstem Right: 2.5cm long, 25 degree takeoff Left: 5cm long, 45 degree takeoff Hard vs soft palate Hard -Stationary Soft -Posterior 1/2 of oral cavity -Rises during eating to prevent aspiration -Sleep/paralytic can cause it to obstruct the nasal passage distance from incisors to carina 26cm incisors and larynx: 13cm distance from larynx to carina: 13cm Pharynx (overall structure and 3 compartments) Extends from the base of the skull to the cricoid cartilage Nasopharynx, oropharynx, and hypopharynx Cricothyroid membrane membrane between the cricoid and thyroid cartilages of the larynx -Membrane that is punctured during cricothyroidotomy Connects cricoid cartilage at C6 to the thyroid cartilage Vocal folds (name, anatomy) True vocal cords -Attach anteriorly to the thyroid cartilage and posteriorly to the arytenoids Space between vocal folds Rima glottidis, goes to the trachea Vestibular folds False vocal cords, around the vocal folds/true vocal cords Superior valeculla Space between base of tongue and epiglottis -Applying force here pulls the epiglottis away from the glottis opening Inferior valeculla Between the inferior ridge of the epiglottis and true vocal cords Epiglottis Single leaf like cartilage, sits above the glottic opening (to the larynx) -Closes during swallowing - Attached to the upper border of the hyoid bone Direct laryngoscopy anatomy -Larynx starts at epiglottis -Internal to larynx=articulating cartilages, arytenoids, epiglottis -Epiglottis, superior, and interior valeculla Larynx (C space and number of cartilages) Starts at C3 to C6 3 single cartilages -3 paired cartilages Branches of Recurrent laryngeal nerve Right-subclavian Left-aortic arch Vagus nerve supply and branches Sensation to the airway below the epiglottis -2 branches innervate the hypopharynx: Superior laryngeal nerve Recurrent laryngeal nerve RLN injury Acute bilateral injury= bilateral paralysis of the vocal cords abductors & acute injury to both RLN = risk for stridor and respiratory distress Unilateral or chronic injury isn't as dangerous. paralysis of ipsilateral vocal cord abductors SLN injury Causes hoarseness b/c cricothyroid muscle cannot be tensed. Larynx muscles Intrinsic -Provides functional movement of cartilages and the vocal cords Extrinsic -Moves larynx as a whole in the neck superiorly and inferiorly intrinsic laryngeal muscles Cricothyroid Vocalis Thyroarytenoid Posterior Cricoarytenoid Lateral Cricoarytenoid Interior arytenoid Cricothyroid muscle "Cords tense" -Tense vocal cords, elongate Tuning fork - key player in larygospasm reflex The only muscle that tenses/elongates the cords Innervation: SLN (external) Vocalis muscle shorten (relaxes) the vocal cord Innervation: RLN Thyroarytenoid muscle "They relax" -Shorten (relaxes the vocal cords Adducts (Narrows glottis) Innervation: RLN Posterior Cricoarytenoid muscle "Please come apart" Abducts Innervation: RLN Lateral cricoarytenoid muscles "Lets close airway" "Let's come together Adducts (narrows glottis) Innervation: RLN Aryepiglottic muscle Closes the laryngeal vestibuletongue extrinsic laryngeal muscles that elevate the larynx Stylohyoid Geniohyoid Mylohyoid Thyrohyoid Digastric Stylopharyngeus extrinsic laryngeal muscles that depress the larynx Omohyoid Sternohyoid Sternothyroid Larynx blood supply From branches of the thyroid arteries Upper 1/2 of larynx Used for peds age 2-6 Provides great visibility directly to the trachea -Strait Jackson blade design with curved distal tip Child: 1 Adult: 2 Wisconsin blade Increases the visual field and decreases the possibility of trauma -Strait spatula, flange expands slightly toward the distal blade BURP maneuver Backward, Upward, Rightward Pressure on thyroid cartilage -Displaces larynx, may improve visualization of the glottis Verify ETT placement Bilateral chest rise Bilateral breath sounds Auscultate stomach ETCO2 Preoxygenation before RSI Healthy patient: Four maximal breaths Patient with lung disease: 3-5 minutes RSI ETT size 1/2 size smaller than normal Use ETT with stylet to maximize chance of easy intubation Modified RSI Allows for gentle ventilation with cricoid pressure maintained LMA cuff pressure <60 cmH2O (target is 40-60) Nerves at risk in overinflation: lingual, hypoglossal, recurrent laryngeal LMA maximum airway seal pressures (leak pressure) Classic LMA: 20cmH2O ProSeal, Supreme LMA (disposable version of proseal): ~30mmHg (slides say >40) igel LMA: ~30mmHg Limit TV to 8mL/kg LMA size in relation to what size of ETT can fit through it LMA 1: 3.5 LMA 1.5: 4.0 LMA 2: 4.5 LMA 2.5: 5.0 LMA 3: 6.0 LMA 4: 6.0 LMA 5: 7.0 LMA 6: 7.0 Double lumen ETT indications Thoracic procedures Control of contamination or hemorrhage Unilateral pathology -bronchopleural or bronchocutaneous fistula -large cyst/bullae -lungs have different compliance (single lung txp or unilateral injury) McGrath MAC video laryngoscope Has a video display mounted on the handle -Sizes 2, 3, 4 correspond to Mac blades Patients at risk of aspiration Full stomach GERD Hiatal hernia NG Morbid obesity DM Pregnancy Use of narcotics Preventing aspiration Antacid preop (bicitra) Reglan Cricoid pressure Mild reverse trendelenberg Working suction Laryngospasm spasm of the laryngeal muscles, causing a constriction. Caused by sensory stimulation by vagus nerve (external branch of SLN or RLN) Laryngospasm risk factors Age < 1 year Hypocapnea Light anesthesia Saliva or blood in the airway GERD Exposure to second hand smoke Recent URI Reflex pathway for laryngospasm Afferent limb: SLN internal branch Efferent limb: SLN external & RLN Tensing of cords: Cricothyroid muscle ADDuction of cords: lateral cricoarytenoid & thyroarytenoid blood supply of nasal mucosa 3 arteries: Maxillary (sphenopalatine) Opthalamic Facial (Septal) Causes of upper airway obstruction 1. tongue: relaxation of genioglossus muscle 2. soft palate: relaxation of tensor palatine muscle 3. Epiglottis: relaxation of hyoid muscle Tongue and soft palette are the primary causes of obstruction upper respiratory tract muscles Airway obstruction is prevented by these 3 dilator muscles: Tensor palatine: Opens the nasopharynx (soft palate) Genioglossus: Opens the oropharynx (tongue) Hyoid Muscle: Opens the hypopharynx (epiglottis) Ways to predicts airway difficulty 1. Bag mask ventilation (BMV);(w/ or w/out jaw thrust maneuver) 2. Direct laryngoscopy (DL) and video laryngoscopy (VL) with tracheal intubation (TI) 3. Supraglottic airway ventilation (LMA) 4. Cricothyrotomy airway placement (e.g., needle or surgical) or tracheostomy Problems or indications of complexity with one or more of these four methods of providing ventilation would indicate a difficult airway. Pharynx extends from the base of the skull to the level of cricoid cartilage Larynx membranes Needle inserted at the base of the palatoglossal arch. Aspiration Air: needle to deep Blood: redirect medially Superior laryngeal block Needle injection at the inferior border of the greater cornu of the hyoid bone. Aspiration of Air: Needle is to deep Transtracheal block Needle advanced caudally through the cricothyroid membrane. Patient inhales during injection, this causes cough which send the local anesthetic up through the cords Pre-anesthetic risk factor for layrngospasm •Active or recent URI •Exposure to second hand smoke •Reactive airway dx •GERD •Age < 1 yr OR risk factor for layrngospasm •Light anesthesia •Blood or saliva in airway •Hyperventilation •Hypocapnia •Surgical procedure involving the airway (tonsillectomy, adenoidectomy, nasal/sinus, laryngoscopy, bronchoscopy, palatal) Movement of neck on ETT Neck Flexion: Tube goes in deeper / nose to chest, tip moves toward carina Neck Extension: Tube come out / nose away from chest, tube moves away from carina (this can be enough to extubate an infant) Lateral head movements will also move the tube away from the carina. 3-3-2 rule •mouth opening should be at least 3 fingerwidths (5cm). •Thyroid Mental Distance (TMD) 3 fingerwidths (6cm) is optimal. •distance from the hyoid bone to the thyroid notch should be at least 2 fingers wide. Mandibular protrusion test Class 1: can bite vermillion with lower incisors Class 2: Lower incisor (LI) line with Upper Incisor (LI) Class 3: LI are behind UI (cannot move further) sniffing position An upright position in which the patient's head and chin are thrust slightly forward to keep the airway open. Head even with chest. Cervical flexion, Atlanto-occipital joint extension Risk Factors for difficult mask ventilation BONES Beard Obese (BMI>26) No teeth (edentulousness) Elderly (>55y) Snoring Risk factors for difficult laryngoscopy/intubation small mouth opening long incisors prominent overbite high, arched palate Mallampati III or IV Retrognathic jaw Inability to sublux jaw (mandibular protrusion test) short thick neck short tmd Reduced cervical mobility Mendleson's Syndrome chemical pneumonitis or aspiration pneumonitis caused by aspiration during anesthesia cricoid pressure Pressure on the cricoid cartilage; applied to occlude the esophagus to inhibit gastric distention and regurgitation of vomitus during RSI Pressure b/f LOC=20 newtons or 2kg Pressure after LOC=40 newtons or 4kg Syndromes w/ large tongue (big tongue) Beckwith syndrome Trisomy 21 Small underdeveloped mandible "Please get that chin" Pierre-Robin Goldenhar Treacher Collins Cri du Chat Cervical Spinal anomalies Kids try gold Klippel-Feil Trisomy 21 Goldenhar HELP position Head elevated laryngoscopy position Used for obese pt's ramping or elevating of head and chest to align the sternum and external auditory meatus on the same horizontal plane. Naso pharyngeal airway contraindications anti-coagulation Le Fort 2 or 3 fracture Basilar skull fracture CSF rhinorrhea Raccoon eyes Periorbital edema the only bone that does not articulate with another bone hyoid Narrowest part of adult airway Vocal cords Cylinder shaped Narrowest part of the pediatric airway cricoid cartilage Funnel shaped Pneumocytes Lung cells Type 1: surface area for gas exchange, tight junctions Type 2: produce surfactant. capable of reproduction. Can produce type 1 cells Type 3: Marchophages Increases as the airway bifurcates 3 categories of inhaled anesthetics -ethers -alkanes -gases 2 classes of ethers and their agents Methyl-isopropyl ether: Sevo Methyl ethyl ether: Iso and Des At atmospheric pressure and room temp what form does each category of inhaled anesthetic take ethers: liquid alkanes: liquid gases: gas Ethers R-O-R (ether bridge) Desflurane Isoflurane Sevoflurane Enflurane Methoxyflurane Ether Alkanes Halothane Chloroform Gases N2O Cyclopropane Xenon Type and number of Halogens Isoflurane: 5 fluorine atoms, 1 Chloride Desflurane: 6 fluorine atoms Sevoflurane: 7 fluorine atoms Des and Iso contain chiral carbons - Sevo does not Isoflurane chemical characteristics heavy Cl atom increases potency twice as potent as Sevo, 5x's as potent as Des the chlorine atom also increase blood & tissue solubility Desflurane chemical characteristics Identical to Iso except instead of a chlorine it has another fluorine making it fully fluorinated This causes: ↓potency (↓oil: gas solubility) -> ↑MAC ↑vapor pressure (↓intermolecular attraction) - requires heated vaporizer ↑ resistance to biotransformation (↓metabolism) Sevoflurane chemical characteristics heavy fluorination decreases potency, but it is still 3x's as potent as Des because of heavy propyl side chain Vapor pressure the pressure caused by the collisions of particles in a vapor with the walls of a container vapor directly proportional to temperature ↑temp -> ↑vapor pressure Boiling point At high altitude a liquid will boil at a lower temp as a function of the reduction in atmospheric pressure Partial pressure Dalton's law the contribution each gas in a mixture makes to the total pressure What is the depth of anesthesia determined by the partial pressure of anesthetic in the brain - NOT the volume percent how does higher altitude effect delivery of Des decreased delivered partial pressure d/t decreased atmospheric pressure - ie an underdose This doesn't actually happen b/c of the vaporizer. partial pressure = %vol x atmospheric pressure (decreased atmospheric pressure decreases the partial pressure) Sevo and soda lime can be unstable in both hydrated and dessicated soda lime -> forms compound A -basis for minimum fresh gas flow Des and Iso and soda lime can form carbon monoxide Des > Iso Physiochemical properties of Sevo Vapor pressure: 157mmHg Boiling point: 59 Molecular wt: 200 g/mol Preservative: No Stable in hydrated CO2 absorber: No Stable in dehydrated CO2 absorber: No Toxic byproduct: Compound A Physiochemical properties of Des Vapor pressure: 669mmHg Boiling point: 22 Molecular wt: 168 g/mol Preservative: No Stable in hydrated CO2 absorber: Yes Stable in dehydrated CO2 absorber: No Toxic byproduct: Carbon Monoxide Physiochemical properties of Iso Vapor pressure: 238mmHg Boiling point: 49 Molecular wt: 184 g/mol Preservative: No Stable in hydrated CO2 absorber: Yes Stable in dehydrated CO2 absorber: No Toxic byproduct: Carbon Monoxide Physiochemical properties of N2O Vapor pressure: 38,770mmHg Boiling point: -88 Molecular wt: 44 g/mol Preservative: No Stable in hydrated CO2 absorber: Yes Stable in dehydrated CO2 absorber: Yes Toxic byproduct: None` Solubility coefficient the ability of the anesthetic agent to dissolve in the blood and tissues -higher -> more soluble -> slower onset/offset -lower -> less soluble -> faster onset/offset Blood:gas coefficient Iso: 1.46 Sevo: 0.66 Des: 0.42 N2O: 0.46 Vessel rich: body mass 10%, CO: 75% Muscle & Skin: body mass: 50%, CO: 20% Fat: body mass: 20%, CO: 10% Vessel poor: body mass: 20%, CO: <1% Vessel rich group (VRG) brain, heart, kidneys, liver, and endocrine glands -b/c of the high CO delivered to these organs they receive the most anesthetic agent during induction and are the first to equilibrate VRG > Muscle > Fat Fat acts as a sink for fat-soluble agents What happens to the partial pressure if the agent continued until it fully equilibrated to all body tissues the partial pressure of each tissue would be equal Uptake of N2O by tissue types minimal - will collect in gas-filled spaces like the middle ear and bowel How are inhaled anesthetics eliminated from the body? -elimination from the alveoli (exhalation is primary) -Hepatic biotransformation (P450) -Percutaneous loss % of hepatic biotransformation per agent Sevo: 2% Iso: 0.2% Des: 0.02% N2O: 0.004% Metabolites of Halothane 20% of halothane is metabolized in the liver, which leads to a build up of TFA -> halothane hepatitis Metabolites of Des and Iso metabolized into inorganic fluoride ions and trifluoroacetic acid (TFA) -much smaller amount than that of Halothane, but there is a possibility it could immune-mediated hepatic dysfunction - more likely in a patient w/ previous TFA exposure Metabolites of Sevo Not metabolized to TFA, but does result in the liberation of inorganic fluoride ions. B/c it undergoes the highest amount of hepatic metabolism of modern agents there is a theoretical possibility that it could result in high-output renal failure (unresponsive to vasopressin) s/s: polyuria, hypernatremia, hyperosmolarity, ↑Cr, inability to concentrate urine Metabolites of N2O for all intents and purposes N2O is not metabolized by the body Concentration effect The higher the concentration of anesthetic delivered, the faster its onset of action -this is also referred to as overpressuring -Only clinically relevant w/ N2O 2 components of the concentration effect: 1. the concentrating effect 2. Augmented Gas inflow The concentrating effect -when a pt is breathing room air, nitrogen is the primary gas in the alveoli -N2O is 34x's more soluble in the blood than nitrogen - when N2O is delivered to the lung it passes from the alveoli into the blood at a much faster rate than nitrogen traveling from the blood into the alveoli. This causes the alveoli to shrink. This increases the relative concentration of N2O in the alveoli. This increase the FA/FI rate of rise. -This is why N2O has a faster rate of rise than Des even though Des is the least soluble Augmented gas inflow -the concentrating effect temporarily reduces the volume of the alveoli -on the second breath, the concentrating effect causes an increased inflow of tracheal gas containing anesthetic agent to replace the lost alveolar volume. This augments the increased FA. This is a very short lived phenomenon as alveolar volume is quickly restored. Ventilation effect The faster you breath, the faster you go to sleep Second gas effect Use a very low solubility agent along with another agent of higher solubility causes faster uptake of the slower drug -the use of N2O during induction will hasten the onset of a second gas -This is because of the concentration effect that N2O has on FA/FI -The rapid uptake of N2O causes the alveoli to shrink which increases the alveolar concentration of the second gas relative to alveolar volume -the relative partial pressure of O2 in the alveoli also increases Diffusion hypoxia only occurs with N2O - fast nitrous diffusion out of the blood and into the lungs displaces oxygen in the alveoli. Cure is to run high oxygen levels at the end of a case -Gas containing areas of the body can contain up to 30L of N2O. This is eliminated from the body in 5 minutes after N2O is d/c'd R->L shunt effect on induction of IV and volatiles IV: Faster (blood bypasses lungs) Volatile: Slower, and worse with insoluble gases (Des) Effect Iso the least (more of the agent is dissoved in the blood) Examples of R->L shunts TOF Foramen ovale Eisenmenger's syndrome tricuspid atresia Ebstein's anomoly Effect of increased cardiac output on induction IV: increases the speed of induction Volatile: decreases the speed of induction (Alveoli don't build up concentration as fast b/c agent is being removed too quickly (think about it being watered down) How much more soluble is N2O than nitrogen 34 x's Nitrogen blood:gas coefficient is 0.014. N2O blood: gas coefficient is 0.46 What happens when a compliant airspace becomes a fixed airspace the pressure starts to increase Compliant airspace: N2O increases volume Fixed airspace: N2O increases pressure Fixed airspaces Middle ear Brain during intracranial procedures Compliant airspaces Pulmonary blebs bowel pneumoperitoneum sulfa hexafluoride bubble in the eye (compromises retinal perfusion) Air bubbles in the blood Use of N2O with retinal bubble d/c N2O 15 min b/f bubble is placed avoid N2O for 7-10 days after SF6 bubble is placed Air bubble: 5 days Perfluoropropane bubble: 30 days Silicone oil bubble: No contraindication Things that do not effect MAC thyroid disease Gender PacCO2 15-95mmHg HTN Physiologic factors that effect MAC Things that increase central neurotransmitter concentration, neurotransmission, and cerebral metabolism increase MAC Things that decreases these things decrease MAC Meyer-Overton Rule lipid solubility is directly proportional to inhaled anesthetic potency -the greater the lipid solubility, the lower the MAC -depth of anesthesia is dependent on the number of anesthesia molecules dissolved in the brain Unitary Theory all anesthetics share a similar mechanism of action, but each may work at a different site Modern anesthetic theory inhalation anesthetics interact with stereoselective receptors stimulate inhibitory receptors - GABA-A Old theory of anesthetic action inhalation agents work at the lipid bilayer Volatile anesthetics effects at their target receptors stimulate inhibitory receptors inhibit stimulatory receptors Inhibitory receptors receptors that anesthetics stimulate GABA-A receptors Glycine channels Potassium channels (causes hyperpolarization) Stimulatory receptors receptors that anesthetics inhibit NMDA receptors Nicotinic receptors Sodium channels (cause depolarization) Dendritic spine function and motility GABA receptors ligand gated Cl- channels (hyperpolarization) - volatile anesthetics increase the duration the channel is open most important site of volatile anesthetic action What is volatile anesthetics site of action for producing immobility Ventral horn of the spinal cord Volatile anesthetics receptors in the spinal cord These cause immobility: Glycine receptor stimulation NMDA receptor inhibition Na+ channels (Immobility is not d/t GABA binding) Site of action for N2O and Xenon NMDA inhibition Potassium 2P channel stimulation (They do not stimulate GABA) VIA pharmacologic effect and target region for unconsciousness Cerebral cortex: higher order cerebral fxns Thalamus: Relay station for input Reticular Activating System: consciousness & arousal VIA pharmacologic effect and target region for Amnesia Hippocampus: Memory formation Amygdala: Emotion, pain response, stress response VIA pharmacologic effect and target region for immobility Ventral horn: upper and lower neurons synapse here VIA pharmacologic effect and target region for analgesia Spinothalamic tract: Nociceptive pain signal along ascending pain pathways are inhibited here VIA pharmacologic effect and target region for Autonomic modulation Pons & Medulla: Control center for autonomic reflex Biochemical effect of VIA Cardiac and Vascular smooth muscle: ↓ Ca++ influx through the sarcolemma and ↓Ca++ release from SR -modulate NO release, inhibit Ach-induced vasodilation, and impair Na+/Ca++ pump ↓ intracellular Ca++ concentration Effect: Myocardial depression and vasodilation Hemodynamic effect of Des ↑HR ↓BP ↓/0 CO ↓SVR HR is increased 5-10% most likely d/t to ↑SNS activation (ie beta 1 stimulation) from respiratory irritation - can lead to tachycardia Hemodynamic effect of Iso ↑HR ↓↓BP ↓ CO ↓SVR HR is increased 5-10% most likely d/t to ↑SNS activation from respiratory irritation Dilates coronary arteries the most - that's why it is thought to cause coronary steal Hemodynamic effect of Sevo 0 HR ↓BP ↓/0 CO ↓SVR (least of the halogenated agents) Hemodynamic effect of N2O ↑HR ↑/0BP ↓CO (potentiated by opioids) ↑SVR Effects are explained by SNS activation Hemodynamic effect of Xenon ↓HR 0 BP 0 CO 0 SVR How do halogenated agents effect cardiac conduction dose dependent fashion ↓ SA node automaticity ↓ conduction velocity through the AV node, bundle -> purkinje system ↑ duration of repolarization by impairing K+outflow - prolongs QT Altered baroreceptor function Uncoupling ↓CMRO2, ↑CBF autoregulation CSF dynamics N2O: ↑CMRO2, ↑CBF How to offset the vasodilatory effects of VIA Hyperventilating, propofol, opioids, barbituates Cerebral metabolic rate is dependent on 1. Electrical activity (60%) 2. Cellular homeostasis (40%) VIA only effect the electrical activity. Once an EEG is isoelectric they cannot suppress CMRO2 any further 1.5-2 MAC is needed to produce isoelectric state cerebral autoregulation The ability of the brain to maintain constant cerebral blood flow despite changes in systemic arterial pressure over a range of 50 to 150 mm Hg High concentration Sevo (2.0 MAC) Can produce seizures-more common w/ pediatric inhalation induction VIA effects on CSF Iso: No effect on production, ↑absorption Des: Little to no effect on production, no effect on absorption Sevo: ↓ production, unknown effect on absorption Types of Evoked Potentials Used to montior the integrity of a neural pathway Somatosensory: SSEP (monitors dorsal column - medial lemniscus) Motor: MEP (monitors corticospinal tract) Visual: VEP Brainstem Auditory: (BAEP) How are Evoked potentials produced Applying current to a neural pathway What amplitude of an evoked potential indicates nerve ischemia Amplitude decreases by > 50% or Latency increases by > 10% VIA effect on evoked potentials decreased amplitude and increased latency N2O makes this worse Other confounding factoring that affect evoked potentials hypoxia hypercarbia hypothermia Ketamine enhances the signal Brain auditory evoked potentials Most resistant to the affects of anesthetics, so any agent can be used What to do if evoked potentials decrease during surgery Maintain good BP, volume expansion, and tranfusion for anemia VIA affect on redheads MAC is increased by 19% d/t mutations in the melanocyte stimulating hormone receptor and an increased production of pheomelanin F(i) inspired gas flow = determined by: -FGF rate -breathing circuit volume -circuit absorption F(A) alveolar gas concentration = determined by: -uptake -ventilation -concentration and 2nd gas effect F(a) arterial gas concentration = affected by: -ventilation/perfusion mismatching Factors that effect the speed of inhaled agent Absorption into plastic (how much is absorbed by tubing etc Flow rate ventilation (RR, TV) Concentration Blood gas solubility (Speed) V/Q problems 2nd gas effect N2O diffusion into closed spaces Cardiac output Oil/gas solubility (potency) metabolism Diffusion hypoxia Peds Obesity Hypothermia Blood gas solubility the higher the solubility the slower the drug Stays dissolved in blood rather than moving into the brain Pharmacokinetics the study of the absorption, distribution, metabolism and elimination of drugs What the body does to a drug How the drug gets to its receptor and then how the drug leaves the body -drug dose and plasma concentration Pharmacodynamics physiological and biochemical mechanism of action of drugs What the drug does to the body -effect site concentration and clinical effect receptor theory=binding causes effect Pharmacobiophasics biophase = effect site -drug concentration in the biophase (not the plasma) determines its clinical effect -plasma concentration and effect site concentration Anesthesia MOA We don't know. We know how they work but not why Modern anesthesia we use small doses of many drugs to minimize s/e and make sure they wear off quickly so people can wake up. therapeutic index the ratio between the therapeutic and lethal dose LD50/ED50 = THERAPEUTIC INDEX Interaction Alteration in the therapeutic action of a drug by concurrent administration of other exogenous chemicals Addition The combined effect of two drugs acting via the same mechanism is equal to that expected by simple addition of their individual actions. 1+1 = 2 Synergistic The combined effect of two drugs is greater than the algebraic sum of their individual effects. Increases efficacy not potency. 1+1 = 3 Potentiation The enhancement of the action of one drug by a second drug that has no detectable action of its own. Penicillin + antidiuretic drug = better anti-infective result b/c penicillin stays in system longer. Usually used to mean synergism 1 + 0 = 3 Antagonism The action of one drug opposes the action of another. Narcan reversing narcotic 1 + 1 = 0 Bioavailability The percentage of a drug contained in a drug product that enters the systemic circulation in an unchanged form after administration of the product. How much of the drug enters the bloodstream. So IV drugs are 100%. Intrathecal drugs have very low bioavailability b/c they don't enter the bloodstream. pKa the pH at which the drug will exist in solution as 50 percent ionized and 50 percent non-ionized. All drugs are salts of a weak acid or base Drug Ionization STEP 1: 1. If pH-pKa = 0 then ratio equals 50% 2. If pH-pKa = 0.5 the ratio equals 75/25% 3. If pH-pKa = 1 or greater then the ratio equals 99/1% To determine whether it's ionized or not: STEP 2 1. acids in acid pH = non-ionized 2. bases in basic pH = non-ionized 3. acids in basic pH = ionized 4. bases in acid pH = ionized Drugs that can pass biological membranes non-ionized If a drug passes a membrane and becomes ionized b/c of a different pH of that body compartment then it is trapped there. ionized Charged, water soluble, can't pass thru membranes non-ionized no charge, lipid soluble, can pass thru membranes The amount of ionization depends on what 2 things -the pH of the solution -the pKa of the drug When the pka of the drug and the pH are the same 50% of the drug will be ionized and 50% will be nonionized Acid in a base solution Base in an acid solution ionized Acid in an acid solution Base in a base solution non-ionized Base If pH > pKa non-ionized predominates If pH = pKa non-ionized = ionized If pH < pKa ionized predominates Acid If pH > pKa ionized predominates If pH = pKa non-ionized = ionized If pH < pKa non-ionized predominates ion trapping when drugs change body compartments, they may become ionized and trapped in the new environment ex. maternal alkalosis (drug in non-ionized) -> drug passes to fetus -> fetus is more acidic & drug becomes ionized -> cannot pass back out (trapped) -as the drug becomes ionized in the fetus it drives a concentration gradient for more non-ionized drug to cross over making the situation worse Full agonist binds to a receptor and turns on a cellular response, mimics endogenous ligand -produces a maximal response -continuous administration may cause down regulation of receptors ex. dopamine, norepi, propofol, dopamine Partial agonist activates a receptor but cannot produce a maximum response (partial cellular response). may also be able to partially block the effects of full agonists by competing for binding sites. -lower efficacy than a full agonist. Antagonist binds to receptors to prevent agonist binding therefore preventing cellular response -does not have efficacy -continuous administration may cause up-regulation of receptors (ex. beta blockers) competitive v non-competitive antagonism Competitive -reversible -shifts the agonist to the right (makes it less potent) -increasing concentration of agonist can overcome competitive antagonism Non-Competitive -irreversibly binds (covalent bond) -effect is not overcome by adding more agonist -ex. ASA (life of platelet) inverse agonist binds to receptor and causes the opposite effect as the agonist -negative efficacy Comprised of central compartment rapidly equilibrating peripheral compartment slowly equilibrating peripheral compartment Half-life the time it takes for 50% of a drug to be removed from the body Half time the time it takes for 50% of the drug to be removed from the plasma Half times are really only applicable to a 1 compartment model which does not exist in real life - drugs distribute into and out of compartments at different rates What 2 things does Vd assume 1. The drug distributes instantaneously 2. The drug is not subjected to biotransformation or elimination b'f it fully distributes Concentration amount of drug in a given blood volume distribution of body water of a 70kg patient Total body water: 42L Intracellular: 28L, Extracellular: 14L Plasma Vol: 4L, Interstitial fluid: 10L Lipophilic drug Drug that Vd exceeds total body water (>0.6L/kg or >42L) Will require a higher does because a lot of it is lost from the plasma into fats Hydrophilic drug Drug that Vd is less than total body water (<0.6L/kg) Will require lower dose because it down not go into fats so there is more in the plasma What drug characteristics affect Vd? Molecular size ionization protein binding How to calculate loading dose Loading dose = (Vd x Desired plasma conc.)/Bioavailability For IV drugs bioavailability is 1 b/c they are injected directly into plasma. So for IV drugs you can take: Vd x desired plasma concentration Context sensitive half time The time for the plasma concentration of a drug to decrease by 50% from an infusion that maintains a constant concentration. The context is the duration of the infusion. A drug with a long context sensitive half time stays in the central compartment longer - fentanyl Flaw with context sensitive half-time it only illustrates the time it takes for the drug to decrease by 50% in the CENTRAL compartment. This is why it does not necessarily predict the time to wake up. b/c it can redistribute into the fat and act like a sink for the drug. Albumin most abundant plasma protein t 1/2 is 3 weeks primary determinant of oncotic pressure measurement for protein synthesis (chronic not acute problems) negative charge primarily binds acidic drugs 3 plasma proteins that bind drugs albumin (acidic drugs) alpha1-acid glycoprotein (basic drugs) beta globulin (basic drugs) Changes in protein binding result from -change in protein concentration -competition for binding sites on the protein plasma protein binding in relation to Vd inversely related 2 factors that affect the rate of metabolism 1. concentration of drug at site of metabolism - influenced by blood flow to the site 2. intrinsic rate of metabolism - genetics, enzyme induction, and enzyme inhibition kinetic models of drug metabolism there is a finite number of enzymes that can metabolize the drug Zero order kinetics Drug elimination with a constant amount metabolized regardless of drug concentration -> constant amount per time -there is more drug than enzymes -examples: ASA, phenytoin, alcohol, warfarin, heparin, theophylline First order kinetics constant percentage of substrate is metabolized per unit time -> constant fraction per time -there is less drug than enzyme -accounts for most of the drugs we give Metabolism (biotransformation) enzymatic process of altering the chemical structure of a molecule -Primary role is to change a lipid soluble molecule into water soluble which has a greater volume of distribution water or lipid soluble drugs Lipid soluble. The more ionized a molecule is the lower volume of distribution it has water soluble = ionized being water soluble and ionized increases the delivery of the molecule to the kidneys. The ionization will prevent reabsorption in the kidney tubules Prodrug An inactive drug dosage form that is converted to an active metabolite by various biochemical reactions once it is inside the body. Fospropofol 3 phases of metabolism most important cytochrome in P450 enzyme - metabolized nearly 50% of all drugs Substrates: opioids, benzos, local anesthetics inducers: tamoxifin, barbituates, St. John's Wort, rifampin, ethanol, carbamazepine inhibitors: grapefruit, SSRI's, cimetidine, erythromycin, azole antifungals CYP 2D6 codeine -> morphine oxycodone hydrocodone -inducers: carbamazepine, phenytoin, dexamethasone -inhibitors: SSRI's, isoniazid, Quinidine CYP 1A2 Theophylline -inducers: tobacco, cannabis, alcohol -inhibitors: erythromycin, ciprofloxacin enzyme inducer stimulates synthesis of additional enzyme -increases drug clearance and decreases half time tobacco smoke barbituates phenytoin rifampin ethanol carbamazepine enzyme inhibitor competes for binding sites on an enzyme -decreases drug clearance and increases half time grapefruit SSRI's cimetidine omeprozole isoniazid erythromycin ketoconazole Renal elimination Hydrophilic drugs (ionized) will be excreted unchanged Lipophilic drugs (unionized) will undergo biotransformation so they can be eliminated or they will be reabsorbed in the kidneys (via diffusion) glomerular filtration and protein binding highly protein bound drugs will not be freely filtered. non-protein drugs will be freely filtered. Organic Anion and Cation Transporters transport proteins in proximal renal tubule actively secrete organic acids and bases into urine organic anion transporters: furosemide, thiazide diuretics, and penicillin organic cation transporters: morphine, meperidine, dopamine Acidic urine favors like dissolves like Reabsorption of acidic drugs Excretion of basic drugs AAA: Acidic drugs are better Absorbed in Acidic urine You can acidify the urine to eliminate basic drugs (ammonium chloride, cranberry juice) Basic urine favors Reabsorption of basic drugs Excretion of acidic drugs BBB: Basic drugs are Better absorbed in Basic urine You can alkanize the urine to eliminate acidic drugs (bicarb, acetazolemide) 4 key metabolic pathways in the plasma pseudocholinesterase Non-specific esterases Alkaline phosphatase Hoffman elimination Drugs metabolized by pseudocholine esterases Succ Mivacurium Ester local anesthetics (one i) Drugs metabolized by Non-specific esterases Remifentanil Esmolol (RBC esterases) atracurium (+Hoffman's) Etomidate (+ hepatic) Drugs metabolized by Alkaline Phosphatases Fospropofol ie. this is prodrug is metabolized by alkaline phosphatase to form the active drug propofol chirality a molecule with one chiral carbon will exist as 2 enantiomers -a carbon bound to 4 DIFFERENT atoms racemic mixture A mixture that contains equal amounts of the (+) and (-) enantiomers. Examples: ketamine, thiopental, methohexital, Iso, Des, Mepivicaine, Prilocaine, bupivacaine, morphine, methadone, ibuprofen, ketorolac Enantiomers molecules that are mirror images of each other -R & S endogenous opioid peptides enkephalins, endorphins, dynorphins You can't synthesize these b/c they don't reach their target tissues and cause anaphylaxis Where are opioid receptors located? Brain: periaqueductal gray, locus coeruleus, and rostroventral medulla Spinal Cord: Primary afferent neurons in the dorsal horn and the interneurons Periphery: sensory neurons and immune cells Opioid target Brain, Spinal cord, GI GI has the largest amount of opioid receptors Nociceptors Receptors that sense pain, respond to substance P, bradykinin. opioid receptors Mu: beta endorphin, met and leu enkephalin Kappa: Dynorphin Delta: met and leu enkephalin ORL-1 receptor: nociceptin Codeine Codeine is a prodrug which is metabolized to morphine. People who are fast metabolizers can end up w/ a toxic level of morphine (respiratory depression). This is why we don't give in to children. CYP2D6 pKa: 8.2 (14% nonionized) Tramadol metabolized to its M1 metabolite with is 6 x's more potent than parent compound. CYP2D6. Also contraindicated in children < 12-18y Phenanthrene alkaloids a. Natural: morphine, codeine, thebaine b: Semisynthetic: Diacetylmorphine (heroin), Hydrocodone, Hydromorphone, Oxycodone, Oxymorphone Semisyth antagonist: Naloxone, naltrexone, nalmefene c. Synthetic: Morphinian derivatives, Benzmorphans Piperidine Derivatives (Phenylpiperdines) a. Phenylpiperdines: Mereperidine, Loperamide b. Anilidopiperidines (no histamine release): Fentanyl, Sufentanil, Alfentanil, Remifentanil Diphenylheptanes Methadone Which Anilidopiperidine has the fastest onset Alfentanil d/t it low degree of ionization (pka: 6.5) - crosses the BBB faster Has a low Vd and high degree of protein binding Opioid allergy All phenanthrene's and Meperidine stimulate histamine release. Allergies are related to chemical class. If you're allergic to one drug in the class, you're allergic to all of them, but you can have one from a different class. Opioid potency Potency is extremely variable b/c of people's differences in pain perception and tolerance. Animal studies: tail click test and hot plate test Order of opioid potency Sufentanil > Fentanyl=Remi > Alfentanil > Hydromorphone > Morphine > Meperidine Which opioid causes skeletal muscle weakness Remi - do not administer in the epidural or intrathecal space Morphine Sulfate Potency Ratio: 1 Analgesia Dose: 10mg Anesthetic Dose: 1-5mg/kg Duration of action: 3-5h pKa: 7.9 (23% nonionized) Protein biding: 35% Vd: 2.8 metabolism: liver, conjugated and eliminated by kidney as a phase 2 product Differences in morphine's affect on women -greater analgesic potency -slower onset of action -longer duration of action -lower postoperative opioid consumption Meperidine Potency Ratio: 0.1 Analgesia Dose: 100mg Anesthetic Dose: NA Duration of action: 2-4h pKa: 8.5 (7% nonionized) Protein biding: 70% Vd: 2.6 metabolized to a CNS toxic metabolite. Not recommended for admin >24h or for renal dx or elderly. Stimulates Mu & Kappa receptors Affect of co-administration of Meperidine and MAOI's Can cause serotonin syndrome b/c Meperidine is a weak serotonin reuptake inhibitor Fentanyl (Sublimaze) Potency Ratio: 100 Analgesia Dose: 100mcg Anesthetic Dose: 50-100mcg/kg Duration of action: 1-1.5h pKa: 8.4 (8.5% nonionized) Protein biding: 84% Vd: 4 Metabolism: CYP3A4 Sufentanil (Sufenta) Potency Ratio: 500-1000 Analgesia Dose: 10-20mcg Anesthetic Dose: 5-20mcg/kg Duration of action: 0.8-1.3h pKa: 8 (20% nonionized) Protein biding: 93% Vd: 2 *most potent opioid, do not give unless you don't plan to extubate after the case. Alfentanil (Alfenta) Potency Ratio: 10-20 Analgesia Dose: 500-1000mcg Anesthetic Dose: 100-200mcg/kg Duration of action: 0.25-0.4h pKa: 6.5 (89% nonionized) Protein biding: 92% Vd: 0.6 Metabolism: Liver CYP3A4 Remifentanil (Ultiva) Potency Ratio: 100 Analgesia Dose: infusion only (0.1-1 mcg/kg/min) Anesthetic Dose: infusion only Duration of action: 2-5 min metabolism: nonspecific esterase, only opioid not affected by liver dx pKa: 7.2 (58% nonionized) Protein biding: 95% Vd: 0.39 dosed at lean body weight d/t metabolism Mu agonist Hydromorphone (Dilaudid) Potency Ratio: 5 (apex says 7) Analgesia Dose: 2mg Anesthetic Dose: NA Heroin Potency Ratio: 2 *causes the most euphoria What drug inhibits alfentanil's metabolism erythromycin (renal failure does not alter alfentanil's clearance) Uses for Meperidine Chronic treatment of opioid abuse Chronic pain syndrome Cancer pain Phase 1 metabolism Oxidation, reduction, hydrolysis Phase 2 metabolism Conjugation reactions in which a polar molecule is linked to a suitable functional group on a drug or one of its Phase 1 metabolites vomiting center depress respiratory center's sensitivity to CO2 (drives ventilation) -shifts CO2 curve to the right. Narcotics increase partial pressure of CO2 in alveoli which decreases RR and VT. Opioids are also antitussives which is helpful in anesthesia. Cause and consequence of chest wall rigidity a/e of high dose narcotic injected quickly (tight chest). It is actually not the chest wall that causes difficulty ventilating, it is laryngeal muscle contraction (caused by mu receptor stimulation in the CNS) Use of N20, elderly, and absence of NMB increase the risk. Only occurs after pt has lost consciousness (ie, so ok to paralyze). Can impair spontaneous ventilation and make controlled ventilation difficult/impossible. Treatment: Succ or naloxone Opioid CV effects -Bradycardia -Blood pressure: minimal effects in healthy pts (synergistic with benzos) -↓BP with Morphine and Meperidine (d/t histamine) -Dose dependent vasodilation -Baroreceptor reflex not affected -Myocardial contractility not affected Opioid neurologic effects -Shifts CO2 response curve to the right and reduces ventilatory response to CO2 -↓RR, ↑Vt (↑PaCO2 increases ICP) -Miosis -Minimal effect on evoked potentials -Chemoreceptor trigger zone stimulation Opioid gastrointestinal effects Contraction of sphincter of Oddi -> ↑biliary pressure N/V Prolonged gastric emptying slowed peristalsis -> constipation Treatment for ↑ biliary pressure Atropine, nitro, glucagon, narcan Agent that causes the most ↑ in biliary pressure Fentanyl (Meperidine causes the least) opioid immunologic effects Histamine release (morphine, meperidine, codeine) Inhibition of cellular and humoral immune fxn Suppression of natural killer cell fxn opioid effects on thermoregulation Resets hypothalamic temperature set point -> ↓core temp Complications w/ Narcan HTN, CVA, Pulmonary edema, Cardiac arrest, VT/VF Narcan Administration Draw up 0.4mg Narcan (1ml) with 3ml sterile water. Give 1 ml at a time. Stop when respiratory depression diminishes. Try to keep dose as low as possible so pt sill has some analgesia affects. Intermittent opioid dosing Each time you give a bump of an opioid you are pushing higher above the apnea line. Doing this puts you at the highest point above the apnea line at the end of the case. If you front load instead it will be high in the beginning, and lower at the end of the case. 4 steps of the pain process 1. Transduction 2. Transmission 3. Modulation 4. Perception pain transduction Begins when tissue is damaged causing the release of chemical mediators which activate peripheral nerves (nociceptors). Those chemical mediators are turned into an action potential that travels along the nerve. Nearby immune cells may also be stimulated to release proinflammatory mediators. A-delta fibers Transmit fast pain that is sharp and well localized C fibers Transmit slow pain that is dull and poorly localized - small nerve fibers, poorly myelinated or unmyelinated Contribution of inflammation to pain -reduce threshold to pain stimulus (allodynia) -increased response to pain stimulus (hyperalgesia) Pain Transmission pain signal is relayed through the three neuron pain pathway along the spinothalamic tract three-neuron afferent pain pathway first order: periphery to dorsal horn second order: dorsal horn to thalamus third order: thalamus to cerebral cortex Cell body locations of three-neuron pain pathway First order: dorsal root ganglia Second order: dorsal horn Third order: thalamus pain modulation pain signals can be inhibited or facilitated as they travel along sensory pathways; this can occur wherever there is a synapse Most important site of pain modulation Substantia gelatinosa in the dorsal horn substantia gelatinosa Descending inhibitory pathway begins in the periaqueductal gray and the rostroventral medulla -the dorsal region of the spinal cord where both fast and slow pain fibers synapse with sensory nerves on their way to the brain Endogenous pain modulation pathway Periaqueductal grey -> Rostroventral Medulla -> Substantial gelatinosa Pain inhibition 1. Spinal neuron release Gaba or glycine 2. the descending pathway releases NE, 5-HT, endorphins Pain augmentation 1. Central sensitization 2. Wind up pain perception processing of afferent pain signals in the cortex and limbic system. Precursors of endogenous opioids Pre-proopiomelanocortin = Endorphins = Mu Pre-Enkephalin = Enkephalin = Delta Pre-dynorphin = Dynorphins = Kappa Tolerance Complication of opioid induced muscle rigidity CV: ↑CVP, ↑PAP, ↑PVR Resp: Hypoxia, Hyercapnia, ↑O2 consumption, ↓SVO2, ↓thoracic compliance, ↓FRC, ↓Minute ventilation ↑ICP, ↑Gastric pressure (w/ masking) Treatment for chest wall rigidity paralysis and intubation Naloxone can also reverse but this is not wise to do prior to surgery Partial agonist opioids Pentazocine Nalbuphine Butorphanol Buprenorphine Benefit of partial agonists Produce analgesia with less risk of respiratory depression Low risk of dependence Can be used in patients who cannot tolerate a full agonist Downside of partial agonists Ceiling effect for analgesia Reduce the efficacy of previously administered opioids Can cause opioid withdrawal is opioid dependent patients Naloxone dose: 1-4mcg/kg (give slowly to prevent overshoot) duration: 30-45min (short) metabolism: liver (significant first pass metabolism) crosses the placenta - (neonatal withdrawal) Naloxone side effects (Effects of reversing the opioid -> pain -> SNS activating) SNS stimulation: tachycardia, HTN, dysrhythmias Neurological: neurogenic pulmonary edema, tremors/seizures, aggressive/combative Gastrointestinal: nausea/vomiting sudden death Naltrexone oral opioid antagonist Duration: 24h unlike naloxone it does not undergo significant first pass metabolism Which opioid antagonist should not be used to reverse respiratory depression? Methylnaltrexone = Does not cross BBB Used to reverse constipation while not reversing analgesia Which opioid antagonist can be used to treat alcohol withdrawal or maintain recovering opioid abusers? Naltrexone Nalmfene Pretty much like naloxone with a longer half life of 10h - can be used to maintain recovery in abusers biliary pressure opioid increase billiary pressure d/t constriction of sphincters. Treatment: Are opioids associated w/ apoptosis in animal models No Drugs that are: N2O, etomidate Order of context sensitive half times for Remi, Fentanyl, Alfentanil, and Sufentanyl Fentanyl (longest) > Alfentanil > Sufentanyl > Remifentanil (shortest) Which opioid should be avoid with a MAO-i Meperidine Its is a weak serotonin reuptake inhibitor so co-administration can lead to serotonin syndrome Which opioid is an NMDA receptor antagonist Methadone AchE inhibitors MOA Reversibly inhibits AchE, increasing the concentration of Ach at the neuromuscular junction allowing it to better compete with NMB's for nicotinic binding. It does not decrease the amount of NMB present - it still needs to be eliminated from the body How does AchE inhibitors increase concentration of Ach at the NMJ receptors 1. Enzyme inhibition 2. Presynaptic effects 3 ways to inhibit AchE 1. Electrostatic attachment -competitive inhibition: Edrophonium 2. Formation of carbamyl esters -competitive inhibition: Neostigmine, pyridostigmine, physostigmine 3. Phosphorylation -noncompetitive inhibition: organophosphates & echothiophate Mechanism for presynaptic effects of reversal agents 1. AchE inhibitors can bind to the presynaptic receptor & increase the release of Ach 2. Inhibition of AchE near the presynaptic receptor increases the concentration of Ach available for binding the presynaptic receptor. Reversal agent effects on pseudocholinesterase Neostigmine and pyridostigmine inhibit pseudocholinesterase (not edrophonium) What will happen if Succ is given after Neostigmine or pyridostigmine The effect of Succ will be prolonged because pseudocholinesterase will be inhibited What is most likely the primary mechanism of inhibition for edrophonium presynaptic Edrophonium dose, onset, duration, metabolism/elimination, best anticholinergic pairing Dose: 0.5-1 mg/kg Onset: 1-2 min Duration: 20-60 min Metabolism/Elimination: Renal 75%, Liver 25% Pairing: Atropine Neostigmine dose, onset, duration, metabolism/elimination, best anticholinergic pairing Dose: 0.02 - 0.07 mg/kg Onset: 5-15 min Duration: 45-90 min Metabolism/Elimination: Renal 50%, Liver 50% Pairing: Glycopyrrolate Pyridostigmine dose, onset, duration, metabolism/elimination, best anticholinergic pairing Dose: 0.1-0.3 mg/kg Onset: 10-20 min Duration: 60-120 min Metabolism/Elimination: Renal 75%, Liver 25% Pairing: Glycopyrrolate Effect of renal failure on reversal agents Prolongs both reversal and NMB's so dosing is the same. Factor that affects onset of action Depth of the block Only possible if 4mg/kg or less was the dose < 4h since reversal -> Roc: 1.2mg/kg > 4h since reversal -> Roc: 0.6mg/kg, Vec: 0.1mg/kg Risks of sugammadex Anaphylaxis: 0.3% of population Bradycardia and cardiac arrest -> give anticholinergics binds oral contraceptives Cerebral Oximetry Utilizes near infrared spectroscopy to measure cerebral oxygenation -measures venous oxygen saturation -detects regional oxygenation (not global) -noninvasive, continuous data Cerebral oximetry function Travels in a elliptical pathway from the emitting diode Arterial and venous hgb absorb different frequencies of infrared light Cerebral blood is 1 part arterial, 3 parts venous (75% venous) ↓oxygen delivery -> ↑cerebral oxygen extraction -> ↓venous hgb saturation What percentage of decline suggests cerebral ischemia >25% from baseline Scalp hypoxia can falsely look like brain ischemia Classification of brain waves EEG provides data about activity of the cerebral cortex EEG can help monitor cerebral ischemia Beta waves awake and alert or "light anesthesia" 13-30cycles/sec high frequency, low voltage Alpha waves 8-12 cycles/sec Awake but restful state, eyes closed Theta waves 4-7 cycles/sec General anesthesia and children during normal sleep Delta waves < 4 cycles/sec General anesthesia, deep sleep, brain ischemia/injury Burst suppression The EEG pattern shows bursts of abnormal activity followed by seconds of flat EEG with no activity. General anesthesia, hypothermia, CPB, cerebral ischemia Isoelectricity No activity Very deep anesthesia and death Brain wave changes during General Anesthesia Induction -> ↑beta activity Light anesthesia -> ↑beta activity Theta and Delta waves predominate during GA Deep anesthesia produces burst suppression At 1.5-2 MAC GA causes isoelectricity N2O affect on EEG ↑beta activity Sevo affect on EEG increase epileptiform activity Etomidate affect on EEG causes myoclonus NOT epileptiform activity Ketamine affect on EEG increases high frequency cortical activity may confuse EEG interpretation development of new delta waves during anesthesia may signify the brain is at risk for ischemia what circumstances mimic cerebral ischemia? Deep anesthesia Hypothermia Hypocarbia Procedures that can benefit from EEG monitoring CEA Cerebral aneurysm AV malformations CPB Deliberate hypotension Barbiturate coma Epilepsy diagnosis and treatment Coma and death Bispectral Index (BIS) 0: absence of cerebral activity 20: Burst suppression 40: Deep hypnotic state 40-60: GA 80: Light to moderate sedation 100: Fully awake N2O affect on BIS increases amplitude of high frequency activity and reduces amplitude of low frequency activity BIS limitations 20-30 sec delay Hypothermia, electromyographic interference (↑muscle tone), & encephalopathy can impair BIS accuracy Less accurate in children Patient State Index monitor Similar to BIS Target range for GA: 25-50 Voltage, Current, Impedance Voltage: Driving Pressure Current: Flow Impedance: Resistance Tip contains active electrode as well as return electrode - there is no return pad Which value is most susceptible to error with oscillatory BP measurement Diastolic BP When does the oscillatory (NIBP) BP measurement not work With non-pulsatile flow (LVAD, CPB) Correct BP cuff bladder size Bladder length 80% of extremity circumference Bladder width 40% of extremity circumference Conditions that cause falsely elevate BP Cuff too small = Cuff pressure required to occlude the artery is higher with a cuff that is too small Cuff is too loose BP measured on extremity below the heart Conditions that cause falsely decrease BP Cuff too large = Cuff pressure required to occlude the artery is lower with a cuff that is too large Cuff deflated too rapidly BP measured on extremity above the heart Changes is SBP and DBP moving from aortic root to periphery SBP increases & DBP decreases, PP widens, MAP remains constant Aortic root: SBP lowest, DBP highest, PP narrowest Dorsalis pedis: SBP highest, DBP lowest, PP widest For every 10cm change in elevation, BP changes by For every inch change in elevation, BP changes by 10cm -> 7.4 mmHg 1 inch -> 2 mmHg Complications of NIBP measurement Pain Neuropathy (radial, ulnar, median) measurement errors Limb ischemia compartment syndrome Bruising Petechiae Interference with IV medication delivery Arterial pressure waveform Systolic BP = peak of waveform Diastolic BP = trough of waveform Pulse pressure = Peak - trough Contractility = upstroke Closure of aortic valve = Diacrotic notch Stoke volume = area under the curve Arterial waveform morphology optimally dampened: baseline re-established after 1 oscillation Under-dampened: baseline re-established after several oscillations (SBP is over estimated, DBP is underestimated, MAP is accurate) Over-dampened: baseline re-established with no oscillations (SBP is under estimated, DBP is over estimated, MAP is accurate) Causes of over-dampening Air bubble Clot low flush bag pressure Where should transducer be leveled right atrium / phlebostatic axis Where is the phlebostatic axis? 4th intercostal space, mid anteroposterior level Why should CVP be measure at end expiration because extravascular pressure equals atmospheric pressure Normal CVP 1-10 mmHg Factors that affect CVP Intravascular volume Venous tone Right ventricular compliance What does a high CVP indicate Hypervolemia Reduced ventricular compliance Increase intrathoracic pressure Factors that increase CPV Transducer below the phlebostatic axis Hypervolemia RV failure Tricuspid stenosis or regurgitation Pulmonic stenosis Pulmonary hypertension PEEP VSD Constrictive pericarditis Cardiac tamponade Factors that decrease CVP Transducer above the phlebostatic axis Hypovolemia Affect of transducer placement on CVP measurement Transducer placed above 0 point underestimates CVP Transducer placed below 0 point overestimates CVP Correct location for CVP catheter tip? above the junction of the superior vena cava and right atrium Distance from insertion site to the junction of SVC and right atrium