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INTRAVENOUS ANESTHETICS
Resident: B.Ankhzaya (MNUMS )
Ketamin
• Ketamine comes as a clear colourless liquid in an ampoule.
 10mg/ml
 50mg/ml
 100mg/ml
Actions:
• Unconsiousness
• An...
• Intravenous (IV)- ind:1-2mg/kg main:0.5
mg/kg
• Intramuscular (IM)-ind:5-10mg/kg, main:3-
5mg/kg
• Oral (sedation)- chil...
Using IV ketamine
• Premedicate with an antisialogogue (e.g.
atropine 10- 20mcg/kg)
• Anaesthesia: give 1-2mg/kg in small ...
Pharmacokinetics of ketamine
Absorption Absorption Well absorbed orally, nasally, rectally and
intramuscularly Oral bioava...
System Effect positive Effect negative
RS • preserves the laryngeal and
pharyngeal reflexes to some
degree
• ketamine is g...
System Effect positive Effect negative
CNS • Ketamine provides very good
analgesia
• Co-administration of opiates or
trama...
System Effect positive Effect negative
Eyes /-/ Ketamine increases intraocular
pressure. The eyes also commonly
move conti...
Patients suitable for ketamine
• Children - nausea, vomiting
and hallucinations are less
common in children
• Burns (repea...
Case 1 A 22 year old man has been admitted with a gunshot wound to the
abdomen. He is shocked from major internal bleeding...
Case 2 Your laparotomy patient (case 1) is back on the ward. He has severe
postoperative pain but you have been unable to ...
Case 3 A 37 year old woman is recovering from 45% burns, she needs dressing changes
every two days which are very painful....
Case 6 An 18 year old girl has been admitted with severe asthma. You have
been asked to see her as she has not improved wi...
• Propofol is slightly soluble
in water , oil-in-water
emulsion
• pH of 6 to 8.5
• In addition to the active
component, th...
10mg/1ml :
 200mg/20ml
 500mg/50ml
 1000mg/100ml
Acting Rapidy ,Short
Induction dose(mg/kg) 1.5-2.5mg/kg(titrated)
Hypnosis dose 100-200mcg/min
Sedation dose 25-75 mcg/min...
Pharmacokinetics of propofol
Absorption Following an IV bolus
Distribution there is rapid equilibration between the plasma...
System Effect positive Effect negative
CVS /-/ • This is mainly due to systemic
vasodilatation
Blood pressure heart rate o...
• Propofol infusion syndrome (PRIS) is defined as acute bradycardia
progressing to asystole combined with lipemic plasma, ...
Death was more likely if the patients were younger than 19 yearsof age, males or
received a vasopressor. Other identified ...
• Sodium thiopentone (also known
as thiopental or pentothal) is
prepared by dissolving a
yellowish powder in sterile water...
Acting Rapidly ,smooth barbiturates
Onset (arm-brain time ) 15—30 sec
Duration 5-10 min
Induction dose 3-7mg/kg
Pain injec...
System Effect positive Effect negative
CNS • Thiopentone can also be used in
Intensive Care patients with head
injuries to...
• 1. Acute intermittent porphyria
• 2. Barbiturate allergy
• 3. Patients with a low circulating blood volume, such as afte...
Thiopentone is metabolised in the liver; less than 1% of the drug appears in the
urine unchanged.
• Midazolam is a water
soluble benzodiazepine. It
comes as a clear solution.
 1mg/ml
 5mg/ml
• Actions: unconsiousness,
...
Acting
Sedation dose 0.05-0.1mg.kg(IV). Short duration
Oral dose (children) 0.5mg.kg Premedication 30min
preoperative
Indu...
System Effect positive Effect negative
CvS /-/ Mild depressant*
RS /-/ Mild depressant *
CNS Anticonvulsant
,antiepileptic...
• Diazepam is exclusively lipid
soluble, water insoluble due to its
carbon-containing ring structure.
• This property make...
Diazepam
Induction dose 0.3-0.6mg.kg
Dose in children 0.2-0.3mg.kg
Onset time 45-60sec
Duration time 15-30min
Pain on inje...
• Etomidate is an imidazole ester.
• It is usually presented as a lipid
emulsion or as a clear solution
containing propyle...
Induction dose 0.2-0.3 mg.kg
Sedation dose 0.03-0.05mg.kg
Onset time 15-45sec
Duration time 3-12min
Pain on injectin +++
R...
System Effect positive Effect negative
CVS • widely used to induce
anaesthesia in the shocked,
elderly or cardiovascularly...
• Etomidate inhibits 11-β-hydroxylase, an enzyme important in adrenal
steroid production.
• A single induction dose blocks...
Weblinks:
1. file:///H:/%C2%A0/Books%20of%20Anesthesiology/Pharmacology%20and%20Ph
ysiology%20for%20Anaesthesia.pdf
2. fil...
Intravenous Agents
Intravenous Agents
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Intravenous Agents

  1. 1. INTRAVENOUS ANESTHETICS Resident: B.Ankhzaya (MNUMS )
  2. 2. Ketamin
  3. 3. • Ketamine comes as a clear colourless liquid in an ampoule.  10mg/ml  50mg/ml  100mg/ml Actions: • Unconsiousness • Analgesia • Amnesia
  4. 4. • Intravenous (IV)- ind:1-2mg/kg main:0.5 mg/kg • Intramuscular (IM)-ind:5-10mg/kg, main:3- 5mg/kg • Oral (sedation)- children:15mg/kg max 500mg It has a slower onset after an i.v. bolus (1-5 minutes). The duration of action depends on the route of administration (20-30 minutes for i.m. and 10-15 minutes for iv). Route of administration
  5. 5. Using IV ketamine • Premedicate with an antisialogogue (e.g. atropine 10- 20mcg/kg) • Anaesthesia: give 1-2mg/kg in small increments initially to avoid episodes of apnoea. For example 30mg boluses every 60 secs to a total of 100mg in a 70kg man. Onset is rapid (1-2 mins) with a duration of 10 minutes. Anaesthesia can be maintained by repeated boluses 0.5mg/kg every 15-20 minutes or by continuous infusion 2-4 mg/kg/hr. • (Add 500mg of ketamine to 500ml of a crystalloid solution. Spontaneous ventilation = 1 drop/kg/min (4mg/kg/hr); Controlled ventilation = 0.5 drop/kg min (2mg/kg/hr). The infusion is stopped roughly 30 minutes prior to the end of surgery.7 • Diazepam 0.1-0.2mg/kg helps to reduce intraoperative movement and also limits postoperative delirium. • Analgesia - 0.5mg/kg produces rapid and profound analgesia Using IM ketamine • Ideal for children and for painful repeated procedures. Atropine can be mixed with ketamine for a single injection. • Anaesthesia: 6-8mg/kg. Onset is gradual over 5-10 minutes and is preceded by intense analgesia. IM titration of maintenance doses is difficult but 5 mg/kg every 30min is usually adequate. An easier technique is to prolong anaesthesia using IV supplements. • Analgesia - 2-4mg/kg. Onset is again 5-10 minutes
  6. 6. Pharmacokinetics of ketamine Absorption Absorption Well absorbed orally, nasally, rectally and intramuscularly Oral bioavailability 20% Distribution Distribution 20-50% protein bound in plasma Volume of distribution 3L/Kg Distribution half life is 11 mins Recovery primarily due to redistribution from brain to periphery Metabolism Metabolism N-demethylation & hydroxylation of the cyclohexylamine ring in the liver Some metabolites are pharmacologically active Excretion Excretion Urinary excretion of conjugated metabolites Clearance 17ml/kg/min Elimination half life 2.5 hours
  7. 7. System Effect positive Effect negative RS • preserves the laryngeal and pharyngeal reflexes to some degree • ketamine is given slowly respiration is usually well maintained(Always have a self- inflating bag and mask available) • no oxygen or only limited oxygen available • Ketamine is an effective bronchodilator. • RR • Saturation decreases when airway obstruction • after rapid i.v. injection the breathing may stop for a short while but usually restarts within a minute. CVS • increase in both blood pressure and heart rate • This is very useful in the shocked patient but in patients with a history of heart attack or angina this can make their heart disease worse. • occasionally there can be a large rise in blood pressure. • patients with ischaemic heart disease, Patients with diabetes should have an ECG, if available, to rule out “silent” ischaemia (ischaemia without chest pain)- avoided Effect of Organ system
  8. 8. System Effect positive Effect negative CNS • Ketamine provides very good analgesia • Co-administration of opiates or tramadol intraoperatively can reduce the amount of ketamine required for maintenance of anaesthesia and therefore reduce the incidence and duration of postoperative hallucinations. • hallucinations can be reduced by premedication with benzodiazepines (usually diazepam 0.15mg/kg orally 1 hour preoperatively or 0.1mg/kg) • dissociative anaesthesia ( patient may have their eyes open and make reflex movements during the operation) • Patients can become tolerant of ketamine. With frequent repeat anaesthetics bigger doses are needed, this tolerance usually wears off over 3 days • Co-administration (however increase the risk of the breathing stopping during the operation.) • Ketamine increases the intracranial pressure and for this reason should be avoided wherever possible in those patients with recent head injuries. GIS /-/ • Ketamine increases salivation. This can lead to airway problems due to laryngeal spasm or obstruction. • It may also make the taping of endotracheal tubes more difficult. To reduce this salivation atropine is usually given either as a premed (20mcg/kg i.m.) 30 minutes preoperatively, or at the time of induction iv (10- 20mcg/kg).
  9. 9. System Effect positive Effect negative Eyes /-/ Ketamine increases intraocular pressure. The eyes also commonly move continually during ketamine anaesthesia (nystagmus). This makes it an unsuitable anaesthetic for eye surgery. Skeletal Muscle /-/ Ketamine increases skeletal muscle tone. This is most prominent after the initial iv bolus and gradually decreases. It is improved by administration of benzodiazepines. It is rarely a problem intraoperatively. Pain on injection No No
  10. 10. Patients suitable for ketamine • Children - nausea, vomiting and hallucinations are less common in children • Burns (repeated painful procedures), trauma, radiotherapy • Shocked patients • Status asthmaticus Patients unsuitable for ketamine • Avoid ketamine with: Hypertension • Ischaemic heart disease • Pre-eclampsia • Raised intracranial pressure • Open eye procedures • Acute porphyrias
  11. 11. Case 1 A 22 year old man has been admitted with a gunshot wound to the abdomen. He is shocked from major internal bleeding and requires a laparotomy. You have a very small supply of inotropes and want to try and not use them. What will you do for induction and maintenance of anaesthesia? • This gunshot victim is shocked and requires a laparotomy, you have limited inotropes. • Ketamine would be an ideal anaesthetic agent in this case due to its cardiovascular effects of raising the blood pressure and heart rate, all other anaesthetic agents tend to have a cardiac depressant effect. • Inductioan can be performed with iv ketamine (1-2mg/kg), atropine (10-20mcg/kg) and diazepam (0.1mg/kg). It is still possible to perform a modified rapid sequence intubation with ketamine, despite its slower onset time. • There are several options for maintenance: • 1) intermittent boluses of iv ketamine (0.5mg/kg) given according to patient’s response - pupil size, heart rate, blood pressure, movement etc • 2) ketamine infusion. Put 500mg of ketamine in a 500ml bag of saline or dextrose. Run this at 1-2mls/min (1-2mg/min). Some patients may require more and others less depending on what other drugs have been given and the type of surgery. Generally the ketamine will need to be discontinued 20-30 minutes before the end of the operation to avoid a long wait for the patient to wake up. This technique for laparotomy is best used with non-depolarising muscle relaxants (avoid pancuronium as combined with ketamine may have very high blood pressure increases). It is however possible, although more difficult, to perform the laparotomy under ketamine alone.
  12. 12. Case 2 Your laparotomy patient (case 1) is back on the ward. He has severe postoperative pain but you have been unable to get any morphine this month. How can you manage his postoperative pain? • ketamine for postoperative analgesia • Ketamine is a very good analgesic and can be a solution for severe pain when morphine is not available. Its use postoperatively is limited by the occurrence of hallucinations, however these are less of a problem when relatively low doses are used. • For adult patients in severe pain a loading dose of 0.5-1 mg/kg i.m. may be given. This can then be followed by an infusion of 60-180mcg/kg/hr (4-12 mg/hr for a 70kg adult). .
  13. 13. Case 3 A 37 year old woman is recovering from 45% burns, she needs dressing changes every two days which are very painful. She has very few sites left for i.v. access and you don’t want to use them as she has further surgery to come. She is also very scared of needles. How will you manage the sedation she requires for her dressing changes? • This woman requires recurrent sedation for painful burns dressings. IV ketamine is possible but in burns patients there are often limited sites for cannulation and these are best saved for trips to theatre. • IM ketamine is also an option but requires relatively large painful i.m. injections. Instead the intravenous preparation of ketamine can be given orally. For an adult give 500mg of ketamine + diazepam 5mg. For a child use 15mg/kg ketamine + 0.2mg/kg diazepam (you can use the i.v. preparation but it tastes very bad and may have to be hidden in juice). The dressing change can usually start after 20-30 minutes. Responses can sometimes be unpredictable and onset time may be slower. • There should always be equipment for suction and face mask ventilation available and if possible, oxygen and a pulse oximeter.
  14. 14. Case 6 An 18 year old girl has been admitted with severe asthma. You have been asked to see her as she has not improved with subcutaneous injections of salbutamol or intravenous aminophylline. She is getting tired and her oxygen saturation is falling. Can you do anything to help? • ketamine for the treatment of asthma • Ketamine is an effective bronchodilator and can be used for the patient who is not responding to conventional bronchodilators such as salbutamol and aminophylline. • The doses of ketamine required are very low and problems with hallucinations rare. A loading dose of 0.2 mg/kg iv is given initially followed by an infusion of 0.5mg/kg/hr for 3 hours. This may be continued if necessary. Close monitoring of the patient is required and an anaesthetist should be available if necessary.
  15. 15. • Propofol is slightly soluble in water , oil-in-water emulsion • pH of 6 to 8.5 • In addition to the active component, the formulation also contains soybean oil (100 mg/mL), glycerol (22.5 mg/mL), egg lecithin (12 mg/mL); and disodium edetate (0.005%) Propofol(2,6 di-isopropylphenol)
  16. 16. 10mg/1ml :  200mg/20ml  500mg/50ml  1000mg/100ml
  17. 17. Acting Rapidy ,Short Induction dose(mg/kg) 1.5-2.5mg/kg(titrated) Hypnosis dose 100-200mcg/min Sedation dose 25-75 mcg/min Onset time 15-45 sec Duration 5-10min Pain injection ++
  18. 18. Pharmacokinetics of propofol Absorption Following an IV bolus Distribution there is rapid equilibration between the plasma and the highly perfused tissue of the brain as described earlier. Plasma levels decline rapidly as a result of redistribution, Metabolism followed by a more prolonged period of hepatic metabolism and renal clearance. The initial redistribution half-life is between 2 and 4 minutes Excretion Excretion Urinary excretion of conjugated metabolites Clearance 20-30ml/kg/min Elimination half life 14-23 hours
  19. 19. System Effect positive Effect negative CVS /-/ • This is mainly due to systemic vasodilatation Blood pressure heart rate or slighty RR /-/ • Act on the respiratory centre to cause respiratory depression. This effect is the most profound with propofol and a period of apnoea is usually seen. (25-35%) • Propofol also markedly reduces airway and pharyngeal reflexes, making it the ideal drug to use with the laryngeal mask CNS • Anticonvulsant in normal doses. • Most minimum vomitin g and naussea CMRO, CBF, ICP reduced Effect of Organ system
  20. 20. • Propofol infusion syndrome (PRIS) is defined as acute bradycardia progressing to asystole combined with lipemic plasma, fatty liver enlargement, metabolic acidosis with negative base excess >10 mmol . l -1, rhabdomyolysis or myoglobinuria associated with propofol infusion Etiology & Risk factors • airway infection, • severe head injury, • high-dose long-term propofol sedation for more than 48 h at more than 5 mg. kg-1. h-1, increased catecholamine and glucocorticoid serum levels • low energy supply • poor oxygen delivery, • sepsis • lipemia, • likely due to a failure of hepatic lipid regulation, possibly related to poor oxygenation or low glucose plasma levels Bradycardia has to be combined with • lipemic plasma, • fatty liver enlargement, • metabolic acidosis with negative base excess >10 mmol . l-1, • rhabdomyolysis or myoglobinuria Symptoms and signs are lactacidosis, arrhythmia, hypotension, renal, cardiac and circulatory failure, oliguria, rhabdomyolysis, elevated serum creatine kinase, serum urea and serum potassium, lipemic plasma, liver enlargement, ketonuria, increased liver enzymes and green or red coloured urine. Propofol infusion syndrom(PRIS)
  21. 21. Death was more likely if the patients were younger than 19 yearsof age, males or received a vasopressor. Other identified risk factors for death were cardiac manifestations, metabolic acidosis, renal failure, hypotension, rhabdomyolysis or dyslipidemia Pathophysiology • PRIS are cytolysis of skeletal and cardiac muscle cells • Muscle biopsies and fat metabolism analyses of patients with PRIS resemble these found in mitochondrial cytopathias and acquired acyl-carnitine metabolism deficiencies by inhibition of beta oxidation. • PRIS may be aggravated by concomitant diseases like cardiomyopathy. • Low carbohydrate supply is a risk factor for PRIS, because energy demand is satisfied by lipolysis if carbohydrate supply is low. Children are more prone to the development of PRIS due to ow glycogen storage and high dependence on fat metabolism.43 Fat overload associated with propofol infusion may also contribute to increased plasma fatty acids Therapy • Propofol infusion must be stopped immediately. • Hemodynamic stabilization has to be achieved by routine intensive care procedures. Unfortunately, bradycardia is often resistant to catecholamines and external pacing. • Carbohydrate substitution is recommended at 6-8 mg.kg.min • Hemodialysis or hemofiltration is recommended for elimination of propofol and its potentially toxic metabolites
  22. 22. • Sodium thiopentone (also known as thiopental or pentothal) is prepared by dissolving a yellowish powder in sterile water to provide a 2.5% solution (ie 25mg/ml). • In this concentration 20mls of solution will contain 500mg. • Ph=10,8 alkaline • Thiopentone can be used as the sole anaesthetic agent for very brief procedures. Thiopentone (thiopentanyl sodium)
  23. 23. Acting Rapidly ,smooth barbiturates Onset (arm-brain time ) 15—30 sec Duration 5-10 min Induction dose 3-7mg/kg Pain injection 0/+ (Pain would suggest extravascular or intraarterial injection) Recovery time Rapidly low incidence of nausea and vomiting. • Following induction anaesthesia is usually maintained by breathing an anaesthetic vapour such as halothane. • Titrate the dose against effect; the loss of the eyelash reflex is a good guide to loss of consciousness.
  24. 24. System Effect positive Effect negative CNS • Thiopentone can also be used in Intensive Care patients with head injuries to control surges in intracranial pressure. • it posesses potent anticonvulsant activity it may be given to treat epileptic seizures • CMRO, CBF GIS and US • It does not have any direct toxic effects on the liver or kidney, but patients with liver or kidney disease may require a lower dose range than 3 to 7 mg/kg. /-/ CVS • it increases heart rate, coronary blood flow, and the oxygen demand of the heart. • Thiopentone directly depresses the contractile force of the heart • can cause hypotension in patients who are hypovolaemic (eg following haemorrhage). • also causes a decrease in venous tone, causing pooling of blood in the peripheral veins; Analgesic and muscle relaxant Thiopentone has no analgesic properties, in fact in low doses it tends to heighten sensitivity to pain. It has poor muscle relaxant properties. /-/ Effect of Organ system
  25. 25. • 1. Acute intermittent porphyria • 2. Barbiturate allergy • 3. Patients with a low circulating blood volume, such as after haemorrhage, are prone to severe hypotension with thiopentone. • 4. Patients with cardiac disease (particularly those with stenotic heart valve lesions) are at risk from the cardiovascular depressant effects of thiopentone. The drug must be carefully titrated against effect. • 5. Patients with partial airway obstruction should not be given an intravenous anaesthetic agent in case total airway obstruction develops. • 6. In severe asthma it is thought that thiopentone may occasionally cause bronchospasm. Contraindications:
  26. 26. Thiopentone is metabolised in the liver; less than 1% of the drug appears in the urine unchanged.
  27. 27. • Midazolam is a water soluble benzodiazepine. It comes as a clear solution.  1mg/ml  5mg/ml • Actions: unconsiousness, sedation , anxiolytic, anticonvulant , amnesia Benzodiazepines(Midazolam)
  28. 28. Acting Sedation dose 0.05-0.1mg.kg(IV). Short duration Oral dose (children) 0.5mg.kg Premedication 30min preoperative Induction dose 0.3mg.kg(0.2-0.4mg.kg IV) Onset time 30-90sec Duration time 10-30min Pain injection /-/ It undergoes hepatic metabolism (+glucorinide or oxidation)and renal elimination. In the elderly, the lower hepatic blood flow and metabolic activity result in a significantly prolonged half life. Liver clearance rate : midazolam >lorazepam >diazepam
  29. 29. System Effect positive Effect negative CvS /-/ Mild depressant* RS /-/ Mild depressant * CNS Anticonvulsant ,antiepileptic CMRO2 and CBF *-dose dependant (monitoring is important duration sedation) When used as a sole induction drug, midazolam causes apnoea in up to 70% of patients The effects of midazolam can be reversed with flumazenil, a competitive benzodiazepine antagonist. This should be given by intravenous injection in 100mcg increments and should act with in 2 minutes. Flumazenil must be used cautiously, as it can cause agitation and seizures Effect of Organ system
  30. 30. • Diazepam is exclusively lipid soluble, water insoluble due to its carbon-containing ring structure. • This property makes it a rapidly absorbed by the oral route but also means that it must be formulated as a lipid emulsion (diazemuls) for intravenous use  5mg/1ml Diazepam
  31. 31. Diazepam Induction dose 0.3-0.6mg.kg Dose in children 0.2-0.3mg.kg Onset time 45-60sec Duration time 15-30min Pain on injectin +++ Diazepam causes cardiorespiratory compromise, particularly when co-administered with opioids.
  32. 32. • Etomidate is an imidazole ester. • It is usually presented as a lipid emulsion or as a clear solution containing propylene glycol at a concentration of 2mg.ml  2mg/ml Etomidate
  33. 33. Induction dose 0.2-0.3 mg.kg Sedation dose 0.03-0.05mg.kg Onset time 15-45sec Duration time 3-12min Pain on injectin +++ Recovery rapid (accompanied by nausea and vomiting) It is rapidly metabolized by hepatic and plasma esterases to yield inactive metabolites. Excretion is predominantly urinary and the elimination half life varies from 1 – 5 hours.
  34. 34. System Effect positive Effect negative CVS • widely used to induce anaesthesia in the shocked, elderly or cardiovascularly compromised patient • Hemodynamic suitable • Least cardiovascular depression of the IV anaesthetic drugs, with only a small reduction in the cardiac output and blood pressure. • Deppressant trombocytes , prolonged bleeding time RS /-/ • causes transient apnoea, though less so than other drugs, and can cause cough or hiccups Post operative nausea and vomiting is common after etomidate administration MOST MINIMUM DEPRESSANT !!!!! Effect of Organ system
  35. 35. • Etomidate inhibits 11-β-hydroxylase, an enzyme important in adrenal steroid production. • A single induction dose blocks the normal stress-induced increase in adrenal cortisol production for 4-8 hours, and up to 24 hours in elderly and debilitated patients. • Continuous infusion of etomidate for sedation in critically ill patients has been shown to increase mortality. • Although no increase in mortality has been identified following a single dose during induction of anesthesia, the use of etomidate has declined in recent years due to a perceived potential morbidity Etomidate
  36. 36. Weblinks: 1. file:///H:/%C2%A0/Books%20of%20Anesthesiology/Pharmacology%20and%20Ph ysiology%20for%20Anaesthesia.pdf 2. file:///H:/%C2%A0/Books%20of%20Anesthesiology/Barash's%20Handbook%20of %20Clinical%20Anesthesia%207th%20Edition.pdf 3. http://www.e-safe- anaesthesia.org/e_library/03/Ketamine_in_anaesthetic_practice_TOTW_027_2006. pdf 4. http://www.e-safe- anaesthesia.org/e_library/03/Induction_drugs_used_in_anaesthesia_Update_2008.p df 5. http://www.e-safe-anaesthesia.org/e_library/03/Thiopentone_Update_1993.pdf 6. https://www.minervamedica.it/en/getfreepdf/7Bgc25XMfY%252FxrQmpROZRCio IEuJjmBgj1OVQvpXO4zG%252B5tbWLZvXw0Ot70ybHmn6VRMbuu9yOvnNu %252FBxEqzYBg%253D%253D/R02Y2009N05A0339.pdf
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