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ICU QUICK DRUG GUIDE
ELSEV1ER
Jennifer Pai Lee
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ICU ICU
QUICK DR UG GUID E
ICU QUICK DRUG GUIDE Editor Jennifer Pai Lee, Pharm.D., BCPS http://icuquickdrug.com ICU
Elsevier
1600 John F. Kennedy Blvd.
Ste 1800 Philadelphia, PA 19103-2899
ICU QUICK DRUG GUIDE, FIRST EDITION ISBN: 978-0-323-68047-9
Copyright © 2021 by Elsevier, Inc. All rights reserved.
Notice
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
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To my soul mate, Joseph, and endearing angels, Jonathan and Joshua.
Foreword
The use of multiple pharmacologic interventions in patients in critical care scenarios requires an in-depth background and often a quick reference source. Working in the intensive care unit (ICU) as a pharmacist for many years, Dr. Lee identified the need for the quick reference to make our significant pharmacologic interventions as accurate and easy as possible. With this goal in mind and as part of her need to help the patients and their care providers, she created the ICU Quick Drug Guide reference book.
The ICU Quick Drug Guide is remarkable in its scope and detail. It is clearly organized and arranged to cover nearly all possible scenarios of the critically ill patients who may cross the doors of the ICU. The book is divided into six sections covering 24 different specific critical scenarios. Each chapter is divided into a brief discussion of drugs used for the specific treatment of the condition and clinical scenario. It is presented in an outline format accompanied by numerous clear descriptive tables of drug dosing, alternative agents, their antidotes (if available), potential complications, and drug interactions that may be encountered.
For the ICU nurses, residents, and physicians alike, this book will become an invaluable reference. For ICU teams rounding together, it will answer questions rapidly and accurately. I can find no other similar reference in medicine and believe that the ICU Quick Drug Guide will become a standard in the industry.
On a personal note, it was my pleasure to assist Dr. Lee in her pursuit of her career goals beyond her initial research studies on drugs for critically ill patients, particularly those involving renal failure and spinal cord injury. Jennifer has devoted her time and training toward the betterment of patients
vi
through education and understanding of how our drugs work, in whom they best work, and in what circumstances problems with our drugs may be anticipated or avoided. I believe all readers will find this book useful and a highly valuable resource.
Morton J. Kern, MD, MSCAI, FAHA, FACC
Chief of Medicine, VA Long Beach Health Care System
Professor of Medicine, University of California, Irvine
Foreword vii
About the Author
Jennifer Pai Lee received her Doctorate of Pharmacy from the University of Southern California School of Pharmacy in 2001. Following graduation, she completed a residency in Clinical Pharmacy Practice at the Long Beach Memorial Medical Center in 2002. She is a Board Certified Pharmacotherapy Specialist and serves as an clinical faculty at University of California San Francisco, University of the Pacific, and University of Southern California Schools of Pharmacy. She has been teaching medical and pharmacy students and residents for almost twenty years as a clinical pharmacist in critical care. Her practice interests include pharmacokinetics, critical care medicine, and cardiology.
Jennifer is currently the Program Manager for Critical Care/Emergency Services at Veterans Affairs Long Beach Healthcare System. She has developed numerous guidelines and protocols that are essential in taking care of critical care patients to the present day. Furthermore, she has received a research grant and has been actively involved in conducting research studies as a principal investigator. She has given several invited presentations at conferences, and has authored many publications in peer-reviewed journals including New England Journal of Medicine and Nephron as a primary and corresponding author.
viii
Preface
As a clinical pharmacist working and teaching for almost 20 years in the intensive care unit (ICU), I have needed to look to different references for different challenging situations. For example, how does one convert opioid dosing when transitioning from home oral oxycodone to intravenous (IV) hydromorphone or IV morphine to transdermal fentanyl? How do we select an anticonvulsant according to a validated clinical practice guideline for a patient in refractory status epilepticus with multiple drug allergies and interactions? What do we choose for an optimal formulary agent within the class of many similar drugs tailored to an individual patient? What source do we use when we are seeking a novel antibiotic for a multidrugresistant pathogen for a specific type of infection?
Now more than ever, there is overwhelming medical information available as reference books, articles, and online resources. However, they may not be readily available or may be too extensive and complex to search for answers while tending to a critically ill patient at bedside. In my experience, there is no single reference that meets the needs of a clinician who seeks urgently precise and accurate, evidence-based medical information while treating patients in the acute care setting. This fact compelled me to write a pocket book that provides the most current ICU drug information based on practice guidelines, along with expert opinions readily available at hand.
Each chapter is uniquely designed to provide a brief discussion of the disease state, followed by treatment algorithms and drug tables that compare and contrast vital information including pharmacokinetics, pharmacodynamics, drug interactions, adverse effects, contraindication, and hepatic/renal dosing along with clinical pearls to help clinicians decide on optimal drug therapy at glance without a delay.
ix
This book is divided into six sections containing the major clinical ICU areas of practice. Section I highlights pharmacotherapy in cardiovascular critical care, including acute coronary syndromes, acutely decompensated heart failure, adult advanced cardiac life support, anticoagulation for atrial fibrillation/flutter, and hypertensive crisis. Section II addresses management of endocrine emergencies such as diabetic ketoacidosis, hyperosmolar hyperglycemic state, and adrenal and thyroid dysfunction. In addition, treatment strategies for acute pancreatitis, hepatic failure, and gastrointestinal complications such as fistulas, postoperative ileus/nausea/vomiting, and bleeding are depicted.
Section III presents empiric and definitive antimicrobial therapy for infections involving the brain, lung, bloodstream, abdomen, urinary tract, and skin and soft tissue. Section IV reviews pharmacotherapeutic interventions in neurocritical care, including, but not limited to, acute ischemic stroke, status epilepticus, and intracranial hemorrhage. Section V discusses treatment pathways for pulmonary disorders such as asthma and chronic obstructive pulmonary disease exacerbations and pulmonary hypertension. Section VI examines pharmacologic therapies for acute poisoning, anaphylaxis, drug-induced hyperthermia, rapid sequence intubation, venous thromboembolism, fluids and electrolytes, and pain, agitation/sedation, and delirium.
I hope this book becomes a valuable resource for all entrylevel clinicians including physicians, pharmacists, nurses, and other healthcare professionals needing a fundamental drug sourcebook while working in ICU, emergency departments, or acute care settings. Furthermore, it can serve as a quick reference that provides a summary or refresher to experienced clinicians working in the hospital setting.
I thank Dr. Morton J Kern for being a magnificent mentor who inspired and advised me throughout the long journey to completion of this book. In addition, I’d like to acknowledge the following invaluable experts for reviewing the chapters:
x Preface
Ali K. Ashtiani, MD: Chapters 1–5
Ellis R. Levin, MD: Chapters 6 and 7
Timothy R. Morgan, MD: Chapters 8 and 9
Karen Tan, PharmD: Chapters 10 and 11
An T. Tran, MD: Chapters 13–15
Marius C. Viseroi, MD: Chapters 12, 16–19, 21–22, and 24
Syeda A. Quadri, MD: Chapters 20 and 23
Morton J Kern, MD: All chapters
Jennifer P. Lee, Pharm.D., BCPS Department of Pharmacy VA Long Beach, Long Beach, California
Preface xi
SECTION 1: CARDIOVASCULAR CRITICAL CARE
1 Acute Coronary Syndromes 3
2 Acutely Decompensated Heart Failure (ADHF) 18
3 Adult Advanced Cardiovascular Life Support 29
4 Anticoagulation for Atrial Fibrillation or Atrial Flutter 41
5 Hypertensive Crisis 48
SECTION 2: ENDOCRINE, GASTROINTESTINAL, AND HEPATIC DISORDERS
6 Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS) 59
7 Other Endocrine Emergencies 65
8 Gastroenterology 73
9 Severe Acute Pancreatitis and Liver Failure 87
SECTION 3: INFECTIOUS DISEASES
10 Abdominal infections 97
11 Other infections 110
12 Sepsis and Septic Shock 164
SECTION 4: NEUROCRITICAL CARE
13 Acute ischemic Stroke (AiS) 181
14 Other Neurocritical Care 189
15 Status Epilepticus 195
SECTION 5: PULMONARY DISORDERS
16 Asthma and Chronic Obstructive Pulmonary Disease (COPD) Exacerbation 207
xii Contents
17 Pulmonary Arterial Hypertension (Group 1 Pulmonary Hypertension) 219
SECTION 6: MISCELLANEOUS
18 Acute Alcohol and Drug Poisoning 237
19 Anaphylaxis 259
20 Drug- induced Hyperthermia 263
21 Fluids and Electrolyte Disorders 268
22 Pain, Agitation, Delirium, and Neuromuscular Blockade in the intensive Care Unit (iCU) 282
23 Rapid Sequence induction 298
24 Venous Thromboembolism (VTE) 303
Contents xiii
SECTIONONE Cardiovascular Critical Care
1
1
Acute Coronary Syndromes
This chapter will review the pharmacologic management of acute coronary syndromes (ACS) according to the 2013 American College of Cardiology Foundation/American Heart Association (AHA) ST-Elevation Myocardial Infarction (STEMI) and 2014 AHA/American College of Cardiology Non-ST-Elevation Acute Coronary Syndromes (NSTE-ACS) guidelines.
3
CLINICAL SIGNS AND SYMPTOMS OF ACS (FIG. 1.1)
Clinical signs and symptoms of ACS:
Chest pain/discomfort radiating to neck, jaws, or shoulders; shortness of breath, nausea/vomiting, indigestion, or new weakness/malaise
Figure 1.1 Presentation a nd D iagnosis of Acute M yocardial I nfarctions. Data from Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394. ACS, Acute coronary syndromes; ECG, Electrocardiogram; NSTEMI, Non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.
4 ICU Quick Drug Guide
12-Lead ECG with non-ST elevation 12-Lead ECG with ST elevation Negative cardiac enzymes Unstable anginaNSTEMI STEMI Positive cardiac enzymes Positive cardiac enzymes
CAUSES OF TROPONIN ELEVATIONS (BOX 1.1)
Box 1.1 Causes of Troponin Elevations
Acute decompensated heart failure
Acute MI
Acute pulmonary embolism
Aortic stenosis
Cardiac amyloidosis
Cardiotoxic chemotherapy
Chest compressions
Chest wall trauma
Chronic heart failure
Direct current cardioversion/defibrillation
Early post–cardiac surgery
Heart transplantation
Myocarditis
Pericarditis
Post-PCI
Rhabdomyolysis
Sepsis
Severe strenuous exercise
Tachyarrhythmia
Type A dissection
MI, Myocardial infarction; PCI, Percutaneous coronary intervention
ACUTE MANAGEMENT OF ACS Goals of Care (Box 1.2)
Box 1.2 Goals of Care
STEMI: REPERFUSION THERAPY
Primary PCI recommended if possible within 90 min of presentation
If primary PCI impossible within 120 min of medical contact, thrombolytic recommended within 30 min of presentation unless contraindicated
Surgical revascularization may be indicated
NSTE-ACS: PREVENT TOTAL OCCLUSION OF THE VESSEL
Revascularization within 24–72 h vs. medical management depending on risk stratification, symptom resolution, and indicators of ongoing myocardial damage/ ischemia
NSTE-ACS, Non-ST-elevation acute coronary syndromes; PCI, Percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction
Data from O’Gara PT, Kushner FG, Ascheim DD, et al. ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362–e425; Amsterdam EA, Wenger NK, Brindis RG, et al. AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394.
CHAPTER 1 Acute Coronary Syndromes 5
Initial Interventions on Presentation of ACS (Box 1.3)
Box 1.3
Morphine
Initial Interventions on Presentation of ACS
2–4 mg IV q5min prn chest pain
Provides analgesia and decreases pain-induced sympathetic tone
Morphine may induce vasodilation and preload reduction
Oxygen 2–4 L/min by nasal cannula or face mask if hypoxemia (SaO2 ,90%), HF, or dyspnea
Use cautiously because it may promote coronary vasoconstriction and generate toxic O2 metabolites
Aspirin 162–325 mg (non-EC) chewed and swallowed immediately, then 81 mg (EC) daily
Nitroglycerin (NTG)
b-Blockers
Inhibit platelet activation
Facilitate coronary vasodilation
NTG 0.4 mg sublingually or spray q5min 33. If continuous ischemic pain, HF, or htn, IV NTG 10 mcg/ min increased by 5 mcg/min q5min to desired effect (NTE 200 mcg/min)
Avoid NTG if:
• SBP ,90 mm Hg or SBP #30 mm Hg below baseline
• Severe bradycardia with HR #50
• HR 100 in the absence of symptomatic HF, or RV infarction
• Oral phosphodiesterase inhibitor within the past 24–48 h
Metoprolol 5 mg IV q5min up to 33 then 25–50 mg
PO q6–12h, transitioned to metoprolol tartrate BID or metoprolol succinate daily
Decreases risk of ventricular arrhythmias and sudden cardiac death post-MI
Improves oxygen flow through the coronary arteries
Initiate within first 24 h of ACS except for:
• Signs of HF or low-output state
• Increased risk of cardiogenic shock (SBP ,120, HR .110 or ,60, age .70)
• Other CI to b-blockade (i.e., active asthma, reactive airway disease, heart block)
6 ICU Quick Drug Guide
Box 1.3 Initial Interventions on Presentation of ACS—cont’d
Acronym
MONA 6
b-Blockers
Morphine
Oxygen
Nitroglycerin
Aspirin
b-Blocker
ACS, Acute coronary syndromes; BID, Twice daily; CI, Contraindication; EC, Enteric coated; HF, Heart failure; HR, Heart rate; htn, Hypertension; MI, Myocardial infarction; NTE, Not to exceed; PO, Orally; RV, Right ventricular; SBP, Systolic blood pressure
Data from Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394.
1 Acute Coronary Syndromes 7
CHAPTER
Additional Intervention in ACS Management of NSTE-ACS (Fig. 1.2)
NSTE-ACS: Definite or likely
Ischemia-guided strategy
Initiate DAPT and anticoagulant therapy
1. ASA (Class I; LOE: A)
2. P2Y12 inhibitor (in addition to ASA) (Class I; LOE: B):
• Clopidogrel or
• Ticagrelor
3. Anticoagulant:
• UFH (Class I; LOE: B) or
• Enoxaparin (Class I; LOE: A) or
• Fondaparinux† (Class I; LOE: B)
Therapy effective
Early invasive strategy
Initiate DAPT and anticoagulant therapy
1. ASA (Class I; LOE: A)
2. P2Y12 inhibitor (in addition to ASA) (Class I; LOE: B):
• Clopidogrel or
• Ticagrelor
3. Anticoagulant:
• UFH (Class I; LOE: B) or
• Enoxaparin (Class I; LOE: A) or
• Fondaparinux† (Class I; LOE: B)
• Bivslirudin (Class I; LOE: B)
Can consider GPI in addition to ASA and P2Y12 inhibitor in high-risk (e.g., troponin positive) pts (Class IIB; LOE: B)
• Eptifibatide
• Tirofiban
Medical therapy chosen based on cath findings
Therapy ineffective
8 ICU Quick Drug Guide
PCI with stenting
Initiate/continue antiplatelet and anticoagulant therapy
1. ASA (Class I; LOE: B)
2. P2Y12 inhibitor (in addition to ASA):
• Clopidogrel (Class I; LOE: B) or
• Prasugrel (Class I; LOE: B) or
• Ticagrelor (Class I; LOE: B)
3. GPI (if not treated with bivalirudin at time of PCI)
• High-risk features, not adequately pretreated with clopidogrel (Class I; LOE: A)
• High-risk features adequately pretreated with clopidogrel (Class IIa; LOE: B)
4. Anticoagulant:
• Enoxaparin (Class I; LOE: A) or
• Bivalirundin (Class I; LOE: B) or
• Fondaparinux† as the sole anticoagulant (Class III: Harm; LOE: B) or
• UFH (Class I; LOE: B)
CABG
Initiate/continue ASA therapy and discontinue P2Y12 and/or GPI therapy
1. ASA (Class I; LOE: B)
2. Discontinue clopidogrel/ ticagrelor 5 days before, and prasugrel at least 7 days before elective CABG
3. Discontinue clopidogrel/ ticagrelor up to 24 h before urgent CABG (Class I; LOE: B). May perform urgent CABG <5 days after clopidogrel/ticagrelor and <7 days after prasugrel discontinued
4. Discontinue eptifibatide/tirofiban at least 2–4 h before, and abciximab ≥12 h before CABG (Class I; LOE: B).
Late hospital/posthospital care
1. ASA indefinitely (Class I; LOE: A)
2. P2Y12 inhibitor (clopidogrel or ticagrelor), in addition to ASA, up to 12 months if medically treated (Class I; LOE: B)
3. P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), in addition to ASA, at least 12 months if treated with coronary stenting (Class I; LOE: B)
Figure 1.2 Management of Non-ST-Elevation Acute Coronary Syndrome. From Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394. †Additional UFH or bivalirudin should be given at the time of PCI because of the risk of catheter thrombosis. ASA, Aspirin; CABG, Coronary artery bypass graft; DAPT, Dual antiplatelet therapy; GPI, Glycoprotein IIb/IIIa inhibitor; NSTE-ACS, Non-ST-elevation acute coronary syndromes; PCI, Percutaneous coronary intervention; UFH, Unfractionated heparin. Class I, Strong recommendation; Class IIa, Reasonable recommendation; Class IIb, May be considered; Class III, No befit; LOE: A, Multiple populations evaluated; LOE: B, Limited populations evaluated.
CHAPTER 1 Acute Coronary Syndromes 9
Oral Antiplatelets (Table 1.1)
Table 1.1 Oral Antiplatelet Therapy
Mechanism of action Inhibits
10 ICU Quick Drug Guide
CLOPIDOGREL PRASUGREL TICAGRELOR
DRUG ASPIRIN
Loading dose 162–325 mg 600 mga 60 mg 180 mg Maintenance dose 81 mg daily 75 mg daily 10 mg dailyb 90 mg BID Prodrug No Yes Yes No Reversible platelet binding No No No Yes Onset 30 min 2–6 h 30 min 30 min Platelet inhibition 10–20% 30–40% 60–70% 60–70%
days
days
days
thromboxane A2-mediated platelet activation Inhibits ADP-mediated platelet activation at P2Y12 receptor
Hold before CABG Do not hold 5
7
5
Comments Non-EC formulation for loading then EC formulation for maintenance Pharmacogenomic variability (CYP2C19) in response
CI: history of stroke/TIA; bleeding risk
Caution: age 75 yr, weight ,60 kg Avoid concomitant ASA .100 mg daily (lack of efficacy)
Notes:
• Aspirin plus P2Y12 for up to 12 months for patients treated initially with an invasive or ischemia-guided strategy
• Aspirin plus P2Y12 for at least 12 months for patients treated with coronary stents
ADP, Adenosine diphosphate; ASA, Aspirin; BID, Twice daily; CABG, Coronary artery bypass grafting; CI, Contraindication; CYP, Cytochrome P450 enzymes; EC, Enteric coated; TIA, Transient ischemic attack
a300 mg loading for #75 yr and no loading for .75 yr receiving fibrinolytic bPatients with weight ,60 kg should receive 5 mg daily
Data from O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362–e425; Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394; Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44–e122; Wijeyeratne YD, Heptinstall S. Anti-platelet therapy: ADP receptor antagonists. Br J Clin Pharmacol. 2011;4:647–657.
CHAPTER 1 Acute Coronary Syndromes 11
Parenteral Antithrombotics for Percutaneous Coronary Intervention (Table 1.2)
Table 1.2 Parenteral Antithrombotics for PCI
Indirect Thrombin Inhibitor
UFH With GP IIb/IIIa inhibitor: 50–70 units/kg
Without GP IIb/IIIa inhibitor: 70–100 units/kg
Direct Thrombin Inhibitor
Bivalirudin (Angiomax)
0.75 mg/kg
Rebolus to maintain goal
ACT during procedure
With GP IIb/IIIa inhibitor: 200–250 s
Without GP IIb/IIIa inhibitor: 250–300 s — Hepatic and RES No
Additional 0.3 mg/kg if needed 1.75 mg/kg/h CrCl ,30: 1 mg/kg/h With or without
GP IIa/IIIa Inhibitors
Abciximab (ReoPro)
Not in U.S. 0.25 mg/kg 0.125 mcg/kg/min
Max: 10 mcg/min 24–72 h; Up to 7 days RES No
12 ICU Quick Drug Guide
DRUG LD (IV) MD (IV) RETURN OF PLT FUNCTION AFTER DC ELIMINATION DIALYZABLE
1 h 80% plasma proteolysis 20% renal Partial
UFH
,50: 1 mcg/kg/min HD: avoid
,60: 0.075
Direct P2Y
Inhibitor
ACT, Activated clotting time; CrCl, Creatinine clearance; DC, Discontinuation; GP, Glycoprotein; HD, Hemodialysis; IV, Intravenously; LD, Loading dose; MD, Maintenance dose; N/A, Not applicable; PCI, Percutaneous coronary intervention; PLT, Platelet; RES, Reticuloendothelial system; UFH, Unfractionated heparin
Data from O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362–e425; Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394; Wijeyeratne YD, Heptinstall S. Anti-platelet therapy: ADP receptor antagonists. Br J Clin Pharmacol. 2011;4:647–657.
CHAPTER 1 Acute Coronary Syndromes 13 Eptifibatide (Integrilin) 180
2 2 mcg/kg/min
4–8 h 50% renal Yes
25
0.15
CrCl
mcg/kg/min 4–8 h 65% renal Yes
mcg/kg q10min 3
CrCl
Tirofiban (Aggrastat)
mcg/kg
mcg/kg/min
Cangrelor (Kengreal) 30 mcg/kg 4 mcg/kg/min 1 h Plasma dephosphorylation N/A
12 Platelet Receptor
Thrombolytics (Table 1.3)
Table 1.3 Thrombolytic Therapy for STEMI
DRUG
Alteplase 15 mg bolus over 1–2 min, then 0.75 mg/kg (NTE 50 mg) over 30 min, then 0.5 mg/kg (NTE 35 mg) over 60 min
Maximum: 100 mg over 90 min
Tenecteplase ,60 kg: 30 mg
60–69 kg: 35 mg
70–79 kg: 40 mg
80–89 kg: 45 mg
90 kg: 50 mg
All doses given as bolus over 5–10 s
Hepatic metabolism
.50% cleared within 5 min after infusion completed, 80% cleared within 10 min
Hepatic metabolism
Half-life elimination: Initial: 20–24 min Terminal: 90–130 min
Original and slow-acting thrombolytic but clinical outcomes are no different
Fast-acting thrombolytic but clinical outcomes are no different
Notes:
• Thrombolytic should be administered within 30 min of hospital arrival
• Administer concurrent aspirin, clopidogrel, and anticoagulant (UFH, enoxaparin, or fondaparinux)
• UFH: 60 units/kg IV bolus, then 12 units/kg/h titrated to target aPTT 1.5–2 times control for 48 h or until revascularization
• Enoxaparin
• STEMI and ,75 yr: 30 mg IV 31 then in 15 min 1 mg/kg subq q12h (max 100 mg for first two doses)
• STEMI and 75 yr: 0.75 mg/kg subq q12h (max 75 mg for first two doses)
• Up to 8 days or until revascularization
• CrCl ,30: same bolus as above then maintenance dose q24h
• Fondaparinux: 2.5 mg IV 31 then 2.5 mg subq daily starting the following day; contraindicated in CrCl ,30
aPTT, Activated partial thromboplastin time; CrCl, Creatinine clearance; IV, Intravenously; NTE, Not to exceed; PD/PK, Pharmacodynamics/pharmacokinetics; STEMI, ST-elevation myocardial infarction; subq, subcutaneously; UFH, Unfractionated heparin
14 ICU Quick Drug Guide
STANDARD DOSING (IV) PD/PK COMMENT
Contraindications (Table 1.4)
Table 1.4 Contraindications to Thrombolytic Therapy
ABSOLUTE CONTRAINDICATIONS RELATIVE CONTRAINDICATIONS
Active bleeding excluding menses
Intracranial neoplasm
Arteriovenous malformation or aneurysm
Suspected aortic dissection
Ischemic stroke within 3 months
Prior intracranial hemorrhage
Significant closed head or facial trauma within 3 months
Intracranial/intraspinal surgery/trauma within 2 months
Bleeding diathesis
Systolic BP .180 mm Hg or diastolic BP .110 mm Hg
Active bleeding in past 4 weeks
Non-compressible vascular punctures
Major surgery in past 3 weeks
Traumatic or prolonged (.10 min) cardiopulmonary resuscitation
Ischemic stroke .3 months ago
Dementia
Active peptic ulcer disease
Pregnancy
Ongoing therapy with warfarin
Data from O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362–e425.
1 Acute Coronary Syndromes 15
CHAPTER
Medical Therapies for Stabilized ACS (Table 1.5)
Table 1.5 Routine Medical Therapies for Stabilized ACS
CLASS INDICATIONS
ORAL DRUG REGIMEN (TARGET DOSE)
b-Blockers All patients without CI Metoprolol tartrate 25–50 mg q6–12h, transitioned to BID of metoprolol tartrate or daily of metoprolol succinatea (200 mg/day)
Carvedilol 6.25 mg BID (25 mg BID)
Bisoprolol 1.25 mg daily (10 mg daily)
ACEI All patients with anterior infarction, post-MI LV systolic dysfunction (EF #40%), or HF
All patients without CI
ARB For patients intolerant of ACEI
Lisinopril 2.5–5 mg daily (10 mg daily)
Captopril 6.25–12.5 mg TID (25–50 mg TID)
Ramipril 2.5 mg BID (5 mg BID)
Trandolapril 0.5 mg daily (4 mg daily)
Valsartan 20 mg BID (160 mg BID)
AVOID/CAUTION
Signs of HF, low output state
Increased risk of cardiogenic shock
Prolonged first-degree or high-grade
AV block
Reactive airway disease
Hypotension
Renal failure
Hyperkalemia
Statins All patients without CI
Atorvastatin 80 mg daily
Hypotension
Renal failure
Hyperkalemia
DDI: CYP3A4, fibrates
Monitor for myopathy, hepatic toxicity
ACS, Acute coronary syndrome; ACEI, Angiotensin converting enzyme inhibitor; ARB, Angiotensin receptor blocker; AV, Atrioventricular; BID, Twice daily: CI, contraindication; CYP, cytochrome P450 enzymes; DDI, Drug-drug interaction; EF, Ejection fraction; HF, Heart failure; LV, Left ventricle; MI, Myocardial infarction; TID, Three times daily.
aSuccinate form rather than tartrate recommended if concomitant non-ST-elevation myocardial infarction, stable HF, or reduced systolic function
Data from O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362–e425.
16 ICU Quick Drug Guide
CHAPTER 1 Acute Coronary Syndromes
References
1 O’Gara PT, Kushner FG, Ascheim DD, et al. ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362–e425.
2. A msterdam EA, Wenger NK, Brindis RG, et al. AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394.
3 Levine GN, Bates ER, Blankenship JC, et al. ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44–e122.
4. Wijeyeratne YD, Heptinstall S. Anti-platelet therapy: ADP receptor antagonists. Br J Clin Pharmacol. 2011;4:647–657.
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