1. Cardiovascular Effects of some IV DRUGS in the ER SHANE BARCLAY JUNE 30, 2015

2. Objectives 1. Review of the Cardiovascular Effects of some IV ER drugs 2. Review of Conscious Sedation drugs and protocols 3. Review of Ventilator Sedation management.

3. Cardiovascular effects of some IV drugs in the ER

4. Remember pharmacology from med school ! Alpha 1 – Agonists cause peripheral vasoconstriction. Antagonists cause vasodilation Alpha 2 – CNS mediated, agonists cause hypotension, sedation… Beta 1 – Heart effects: inotropic (strength of contraction), chronotropic (heart rate), dromotropic (‘conduction’) Beta 2 – Lung effects: Agonists cause bronchodilation. Antagonists cause bronchoconstriction

5.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Phenylephrine +++

6. Phenylnephrine Uses: cardiogenic shock, decompensated atrial fib, diastolic heart failure.. Can be used as a bolus or infusion, although usually it is used in small boluses.

7.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++

8. Epinephrine Uses: ACLS – V. Fib/V-Tach, asystole (1:10,000 solution IV) Uses: Anaphylaxis – (1:1,000 solution S.C. ) Pressor: post intubation As a pressor can be given as an IV bolus or infusion.

9. Mixing Phenylephrine and Epinephrine Phenylephrine: With a 5 ml syringe, draw 1 ml of 50mg/ml (1 vial) Phenylnephrine. Mix it in 100 cc minibag of normal saline Draw out 3 – 5 cc of solution. This is now Phenylephrine of 100 mcg/ml Put labels on both the minibag and the syringe Dose is 50 – 100 mcg/min ie give 0.5 – 1 ml q2-5 minutes. Action is within 1 minutes and lasts for 10-20 min.

10. Mixing Phenylephrine and Epinephrine Epinephrine: Take a 10 cc N/S syringe. Discard 1 cc. Take a preloaded syringe of Epi 1:10,000 from the cardiac drawer. Take the bottom stopper off the syringe. With the 9 cc Saline syringe, draw out 1 cc Epi (1:10,000) You now have 10 mls of Epinephrine 10 mcg/ml Dose is 0.5 – 2 ml (5-20 mcg) q 2-5 min Onset 1 minute, duration 2-5 minutes.

11.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++ Norepinephrine +++ ++ ++ ++ +

12. Norepinephrine Dosage “Up to Date” Dosages Hypotension/Shock Start 0.1 mcg/kg/min – (range 0.1-1.5 mcg/kg/min) Sepsis Start 0.01 mcg/kg/min (range 0.01 – 3 mcg/kg/min)

13. Norepinephrine Dosage “One starting dose” 0.03 mcg/kg/min then titrate.

14.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++ Norepinephrine +++ ++ ++ ++ + Dobutamine ++ ++ +

15. Dobutamine The “cardiac squeeze” drug Start 2 mcg/kg/min

16.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Dopamine Dopaminergic: 0.5-2 mcg/kg/minRenal V/D Beta 1 effects: 2-10 mcg/kg/min + + Alpha effects: > 10mcg/kg/min +

17.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Digoxin + - Atropine + +SA/+AV

18. Atropine and Scopolamine Anticholinergic antimuscarinic In addition to increasing heart rate can cause dry mouth, urinary retention, blurred vision, mydriasis, reduce bowel spasm, agitation, confusion, drowsiness and amnesia. Use prior to intubation?

19.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Digoxin + - Atropine + +SA/+AV Calcium +

20. Calcium - indications 1.Hypocalcemia 2.Calcium channel blocker overdose 3.Hemorrhagic shock 4.Hyperkalemia 5.Hypermagnesemia

21. Calcium – 2 Forms Calcium Chloride Is in the crash cart. Quickly cleaved in the plasma to free Calcium and Chloride Usual dose is 1-2 gm (but can be as much as 4-5 gm) Is usually recommended to be given via a central line or a Very good antecubital vein. Injection into tissue/interstitial can cause necrosis and sloughing.

22. Calcium – 2 Forms Calcium Gluconate Now kept upstairs Metabolized in the liver to free calcium Usual dose is 3 times that of CaCl (ie 3 -6 gm) Can be given through a peripheral IV line.

23. Calcium – Administration Calcium Chrolide Comes in 1 gm/10 ml vial Give maximum 1 ml/minute – i.e. 10 minutes Calcium Gluconate Give 3 gm over 15-20 minutes.

24.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Dihydropyridone- Nifedipine - - - Arterial V/D No venous V/D Non-Dihydropyridone (Phenylakytlamine) Verapamil - - - - Min. Art V/D Non-Dihydropyridone (Benzothiazepine) Diltiazem - - - Arterial V/D Amiodarone + -

25. Using Diltiazem versus Amiodarone Diltiazem has negative inotropic and chronotropic effects, but does inhibit the SA and AV node to treat arrhythmias. Amiodarone has positive inotropic effects along with negative dromotropic effects on both the SA and AV node.

26. Decompensated Atrial Fibrillation Patient presents with rapid Atrial Fibrillation. Heart rate is 185 bpm. BP 80/40 MAP 53 Treatment options? Sure can try cardioversion, but it usually doesn’t work.

27. Decompensated Atrial Fibrillation Get BP and MAP up first Phenylephrine 50 -100 mcg aliquots until systolic at least up to 90 or ideally MAP up to 60-65. Then give Amiodarone 150 mg IV bolus then drip or Diltiazem 2.5 mg/min until HR > 100 or maximum 50 mg.

28.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Beta Blockers _ _ _ _-SA/AV -

29.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Beta Blocker - - - - - SA/AV - Epinephrine ++ +++ ++ +SA/AV ++

30. Clinical Scenario 58 year old presents with anaphylaxis after inadvertently eating shellfish, to which he has a known severe allergy. Past Hx: type 2 diabetes, AMI 1 yr ago. Meds: Metformin, Atorvastatin, ASA, Ramipril, Metoprolol, Pantoloc. 105/68, HR 78, Sats 92% Management: You start IV, give 0.5 mg Epinephrine 1:1000 IM No response to the Epi. What do you do now?

31. Glucagon Promotes gluconeogenesis Promotes production of cAMP (including in the myocardium) Therefore can ‘get around’ beta blockade. Used for impacted food bolus in the esophagus, hypoglycemia, blocker overdose or in patients on beta blockers having anaphylactic reactions Dose: 1 – 2 mg Glucagon IV

32.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Beta Blockers _ _ _ _-SA/AV - Nitroglycerine Low dose ven V/D High dose art V/D + + +

33. Nitroglycerin Predominately a venodilator, but at high doses is also an arteriodilator. Reduce preload and afterload. Preload reduction (venous V/D) decreases myocardial O2 demand. Afterload reduction increases stroke volume and ejection fraction Active metabolite is Nitric Oxide (not nitrous oxide!)

34. Nitroglycerin – bioavailability Oral table Nitro - < 1% bioavailable due to liver metabolism. SL nitro – onset within 1-2 minutes and is about 30-40% bioavailable. So a 400 mcg spray dose has about 100 + mcg plasma level for 4-5 minutes Nitro patch – takes 15 minutes before any plasma level is detectable and peaks by 3-4 hours. Is about 60-70% bioavailable. So a 400 mcg patch will have about 250 mcg plasma level but will take up to 2 hours to attain that level.

35.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Beta Blockers _ _ _ _-SA/AV - Nitroglycerine Low dose ven V/D High dose art V/D + + + ACE Inhibitors - +

36.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Beta Blockers _ _ _ _-SA/AV - Nitroglycerine Low dose ven V/D High dose art V/D + + + ACE Inhibitors Mg Sulfate - + +

37.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Phentolamine ++

38. Phentolamine Use in extravasation injuries from vasopressors (ie norepi, vasopressin, epinephrine..) Prevention: 1.Avoid hand and wrist IVs for pressors 2.Avoid lousy IV’s generally for pressors 3.Can add 10 mg Phentolamine to each liter of IV solution containing norepinephrine. 4.Did I mention avoiding crappy peripheral IVs?

39. Phentolamine Treatment Steps: 1.Stop the IV but don’t remove it. 2.Start the vasopressor in another line. 3.Suck out as much as you can from the blown IV. 4.Comes in 5 mg per 1 ml vial. Place in 9 ml of N/S 5.Administer up to 0.2 mg/kg into the catheter and S.C. around the site 6.Watch for systemic hypotension (should be on a pressor) 7.Call plastics.

40.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Ketamine _+ +

41. -Interacts with at least 10 different receptors. -One of these are the opioid receptors -Negative inotrope but due to secondary CNS simulation causes increase in pulmonary BP, heart rate, cardiac output and myocardial O2 demand. -Usually there will be no change in systemic vascular resistance. -Possesses bronchodilator activity. -Does not increase ICP. (NeuroCritCare Aug 2014)

42. Ketamine Dosing -Analgesic dosing (sub dissociative) – 0.1 - 0.2 mg/kg -Procedural sedation – 0.25 – 0.5 mg/kg. Can be associated with ‘nightmare’ like haze. -Dissociative dose – 1 – 2 mg/kg -Withdrawal agitation associated more with younger age, co- morbidity and dose. (~15-35%)

43.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Ketamine _+ + Fentanyl _

44. Usually has minimal or no effect on BP, LV Pressure and cardiac output. Initial boluses can decrease MAP. May have some negative Chronotropy (decrease HR) that can be treated with atropine. Addition of benzodiazepines can cause CV depression

45. Alfentanil Opioid analgesic 1/4 - 1/10 as potent as Fentanyl. Can be used in sublingual form for pain control Single injection can last up to 30 minutes, S.L. 10-15 minutes. Usual dose is 8- 40 mcg/kg IV, 0.56 mg SL Onset of action IV is 4 times faster than Fentanyl Very few CV effects other than bradycardia Side effects can be respiratory depression, muscle rigidity

46. Remifentanil Opioid analgesic Approximately twice as potent as Fentanyl. Usually used as an infusion. Very short half life ~ 4 minutes (1 – 11 minutes) Causes decrease HR, BP, RR, tidal volume. Side effects can be muscle rigidity (dose and speed related), pruritus

47.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Ketamine _+ + Fentanyl _ Morphine _ ++

48. Morphine Lowers BP via decreasing alpha adrenergic tone mediated through the CNS.

49.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Ketamine _+ + Fentanyl _ Morphine _ ++ Propofol ++

50. Propofol Can cause large reduction in MAP via venous and arterial vasodilation. It also blocks normal baroreceptor mediated tachycardia which would normally counteract these changes.

51.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Ketamine _+ + Fentanyl _ Morphine _ ++ Propofol ++ Midazolam

52. Has minimal CV effects.

53. In the pipeline Etomidate -Hypnotic amnestic drug with no analgesic properties -Onset of action within 1 minute, lasts 3-5 minutes -Minimal CV or pulmonary effects except in the elderly. Dexmedetomidine Alpha 2 receptor agonist Used in ICU by continuous infusion on ventilated patients

54. Questions?

55. Procedural Sedation The biggest obstacles for emergency physicians to effectively and safely treat patients with analgesia and sedation are: Hospital Bureaucracy and Anesthesiologists

56. Procedural Sedation ACEP October 2013 – “Procedural Sedation and Analgesia in the Emergency Department” 1.Does preprocedural fasting reduce risk of emesis or aspiration? n0 – preprocedural fasting has not shown to reduce the risk of emesis or aspiration. (level B) 2. Does capnography reduce the incidence of adverse respiratory events? - capnography may detect hypoventilation and apnea earlier than oximetry and/or clinical assessment. (level B)

57. Procedural Sedation ACEP October 2013 – “Procedural Sedation and Analgesia in the Emergency Department” 3. What is the minimum number of personnel necessary to manage sedation complications? Besides the attending physician, one other nurse or qualified individual should be present for sedation. (level C) 4. Can Propofol and Ketamine be safely administered in the ER for sedation? Ketamine can be safely administered to children. Propofol can safely be administered to children and adults. (level A)

58. Procedural Sedation Pre-oxygenate with non re-breather for 5 minutes. Will delay/blunt the O2 saturation measurements. Use EtCO2 – more sensitive for apnea/hypoxia

59. Procedural Sedation First – consider the degree of sedation you want and the implications. Can be from simple IM/PO analgesia, which is sedating, to full general anesthesia.

60. Procedural Sedation Minimal sedation Analgesia Moderate sedation “conscious sedation” Deep sedationGeneral Anesthesia Responsiveness Airway Spontaneous ventilation

61. Procedural Sedation Moderate sedation “conscious sedation” Deep sedation Responsiveness Purposeful response to verbal or tactile stimulation Purposeful response following repeated or painful stimuli Airway No intervention required Intervention may be required Spontaneous ventilation AdequateMay be inadequate

62. Procedural Sedation In recent years, the most common PSA medications have been Midazolam and Fentanyl. These were used for ‘deep sedation’ procedures ie fracture reduction etc. However, as per the previous slide, responsiveness is often only to painful or repeated stimuli. Once the procedure is complete, you can still have 30 +/- minutes of deep sedation on board. This is traditionally when interventions for airway and ventilation could/did occur.

63.  1  1  1 Drug  1 Inotr Chron Dromo  2 V/C V/D Ketamine _ + + Fentanyl _ Morphine _ ++ Propofol ++ Midazolam

64. Midazolam and Fentanyl ER literature is suggesting using this combination in lower doses for ‘moderate sedation’ that traditionally only local anesthesia or nothing was given. i.e. I&D of abscess, LP, complex lacerations, road rash debridement, burn dressings …

65. Propofol Dr. James Miner Chief of Emergency Medicine Hennepin County Medical Center, Hennepin, Minnesota.

66. Dr. James Miner Miner, James R, Mark Danahy, Abby Moch, and Michelle Biros. 2006. Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department. Annals of emergency medicine, no. 1 (September 25). http://www.ncbi.nlm.nih.gov/pubmed/16997421. http://www.ncbi.nlm.nih.gov/pubmed/16997421 Miner, James R, Richard O Gray, Jennifer Bahr, Roma Patel, and John W McGill. 2010. Randomized clinical trial of propofol versus ketamine for procedural sedation in the emergency department. Academic emergency medicine: official journal of the Society for Academic Emergency Medicine, no. 6. doi:10.1111/j.1553-2712.2010.00776.x. http://www.ncbi.nlm.nih.gov/pubmed/20624140. http://www.ncbi.nlm.nih.gov/pubmed/20624140 Miner, James R, Richard O Gray, Dana Stephens, and Michelle H Biros. 2009. Randomized clinical trial of propofol with and without alfentanil for deep procedural sedation in the emergency department. Academic emergency medicine: official journal of the Society for Academic Emergency Medicine, no. 9. doi:10.1111/j.1553-2712.2009.00487.x. http://www.ncbi.nlm.nih.gov/pubmed/19845550. http://www.ncbi.nlm.nih.gov/pubmed/19845550 Miner, James R, Marc L Martel, Madeline Meyer, Robert Reardon, and Michelle H Biros. 2005. Procedural sedation of critically ill patients in the emergency department. Academic emergency medicine: official journal of the Society for Academic Emergency Medicine, no. 2. http://www.ncbi.nlm.nih.gov/pubmed/15692132.http://www.ncbi.nlm.nih.gov/pubmed/15692132 Miner, James R, Johanna C Moore, Erin J Austad, David Plummer, Laura Hubbard, and Richard O Gray. 2014. Randomized, double-blinded, clinical trial of propofol, 1:1 propofol/ketamine, and 4:1 propofol/ketamine for deep procedural sedation in the emergency department. Annals of emergency medicine, no. 5 (October 16). doi:10.1016/j.annemergmed.2014.08.046. http://www.ncbi.nlm.nih.gov/pubmed/25441247. http://www.ncbi.nlm.nih.gov/pubmed/25441247 Miner, James R, Johanna C Moore, David Plummer, Richard O Gray, Sagar Patel, and Jeffrey D Ho. 2013. Randomized clinical trial of the effect of supplemental opioids in procedural sedation with propofol on serum catecholamines. Academic emergency medicine: official journal of the Society for Academic Emergency Medicine, no. 4. doi:10.1111/acem.12110. http://www.ncbi.nlm.nih.gov/pubmed/23701339. http://www.ncbi.nlm.nih.gov/pubmed/23701339

67. Propofol – key points 1.Propofol for short procedures (2-3 minutes) in a stable patient is safer than any other sedation medication. 2. Use Pre- procedural analgesia rather than peri-procedural. 3. Use 1 – 2 mg/kg Propofol. 4. Use less in the elderly, especially if they have opioids on board. 5. Use more in thin and obese patients. 6. Use less in volume depleted patients. 7. Need to wait 60 seconds (by the clock!) before giving a second dose

68. Propofol 8. Patient will have 30 – 60 seconds retrograde amnesia. 9. Amnesia is while Propofol is starting to work, NOT when it is wearing off. 10. After the first dose of 1.5 mg/kg the patient may still be talking etc, but as long you have the given the patient adequate pre-analgesia, they will have amnesia for the event.

69. Ketamine Can be used to start and maintaining anesthesia, sedation, analgesia, amnesia and treatment of bronchospasm. Acts on many receptors, one of which are the opioid receptors. Can be used is sub dissociative doses for pain. Downside is the psychological reactions as it wears off – agitation, confusion, psychosis. ‘Recovery agitation’ is associated with dosage, younger age and co-morbid conditions, thus ranging from 15-35%.

70. Ketamine Historically recommended for intubation of asthmatics and head injury patients as it causes bronchodilation and does not increase ICP. Now is recommended for procedural sedation in children and adults. Can be used for the above as well as RSI in hypotensive trauma patients. In combination?

71. A Procedural Sedation Protocol? 1.Have a PSA check list 2.Pre-oxygenate with non rebreather for 5 minutes 3.Use SpO2 and EtCO2 monitor 4.Have at least one other person – nurse 5.Plan your procedure before you give the drugs 6.Use pre- procedure analgesia – fentanyl, morphine, hydromorph … 7.Bolus Propofol 1 -1.5 mg/kg. 8.Do the procedure

72. PSA Checklist One example in your handouts.

73. Questions ?