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Shock Syndromes II Mahmoud A. Ammar, Pharm.D., MBA, FCCM, BCCCP, BCPS Yale New Haven Hospital New Haven, Connecticut…

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Shock Syndromes II Shock Syndromes II Mahmoud A. Ammar, Pharm.D., MBA, FCCM, BCCCP, BCPS Yale New Haven Hospital New Haven, Connecticut…

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Learning Objectives 3 min

Shock Syndromes II Learning Objectives 1. Identify critical determinants affecting oxygen delivery and the physiologic response to hypovole- mic and obstructive shock. 2. Evaluate resuscitation str…

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Shock Syndromes II A. Elevated INR and hematemesis. B. Sinus tachycardia and elevated serum creatinine. C. Low hemoglobin and cold and clammy extremities. D. Low Scvo2 and hyperlactatemia. 3…

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Shock Syndromes II 6. Which would best categorize R.M.’s PE? A. High risk. B. Intermediate-high risk. C. Intermediate-low risk. D. Low risk. 7. After initiating therapeutic heparin and monitorin…

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Exam Content Outline 1 min

Shock Syndromes II BPS Critical Care Pharmacy Examination Content Outline This chapter covers the following sections of the Critical Care Pharmacy Examination Content Outline: 1. Domain 1: Critical C…

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Data Tables 3 min

Shock Syndromes II I.  HYPOVOLEMIC SHOCK A. Etiology and Epidemiology 1. Hypovolemic shock is a result of reduced intravascular volume (i.e., reduced preload), which, in turn, reduces stroke volume…

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Shock Syndromes II b. Plasma loss (nonhemorrhagic): Loss of extracellular fluid (e.g., burns, pancreatitis, third spacing, peritonitis, vomiting, diarrhea) 2. The estimated blood volume for a patie…

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Shock Syndromes II C. Acute Traumatic Coagulopathy (ATC): 1. There is no consensus regarding values defining traumatic coagulopathy, and various definitions exist. However, it is commonly defined…

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Shock Syndromes II a. Standard coagulation laboratory or viscoelastic tests are recommended as monitoring techniques to characterize ATC (European Trauma Guidelines, grade 1C recommendation). b. Vi…

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Shock Syndromes II TEG Tracing Characterize Treatment Factor deficiency Plasma -or- prothrombin complex concentrate Platelet dysfunction Platelet transfusions -or- desmopressin Table 3. TEG Output P…

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Shock Syndromes II D. Coagulopathy of Chronic Liver Disease 1. Patients with chronic liver disease often have episodes of clinically meaningful bleeding events confounded by decreased concentration…

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Shock Syndromes II f. Recommendations: Isotonic crystalloids are indicated in hemorrhagic shock. In trauma, restricted volume replacement, usually less than 1.5 L of a balanced crystalloid, should b…

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Shock Syndromes II b. Similar to other shock states, a relative arginine vasopressin deficiency develops in hemorrhagic shock that is associated with catecholamine resistance, vasoplegia, and increa…

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Shock Syndromes II 3. The 2008 American Burn Association (ABA) practice guidelines for burn shock resuscitation promote fluid resuscitation to target a urine output of 0.5–1 mL/kg/hour in adults, wi…

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Shock Syndromes II b. Therefore, treatment of the acutely bleeding patient should prioritize warming the patient to a temperature greater than 93.2°F (34°C), correcting acidosis to a pH greater than…

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Shock Syndromes II b. In contrast, the benefits of prehospital plasma may not be as apparent in an urban setting with short prehospital transport times. In a single-center study at Denver Health Med…

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Shock Syndromes II 7. Some metabolic complications are associated with massive transfusions that are notable for pharmacotherapy considerations. a. Potassium abnormalities may include hypokalemia o…

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Shock Syndromes II ii. The number needed to treat is 67, and no difference between groups was noted in the risk of vascular occlusive events. iii. In a separately published exploratory analysis, th…

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Shock Syndromes II h. Tranexamic acid in postpartum hemorrhage: i. In the WOMAN trial, a tranexamic acid 1-g bolus (which may be repeated at 30 minutes if bleeding persisted after the initial dose)…

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Data Tables 4 min

Shock Syndromes II 2. Kcentra, a nonactivated 4F-PCC, has U.S. Food and Drug Administration (FDA)-approved labeling for use in the reversal of warfarin-related acute bleeding disorders (further disc…

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Shock Syndromes II Patient Case Questions 3 and 4 pertain to the following case. D.R. is a 37-year-old man with an unknown medical history who presents after a helmeted motorcycle collision into a de…

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Shock Syndromes II ii. Hemodynamic instability is defined as a mean arterial pressure (MAP) less than 65 mm Hg, SBP less than 90 mm Hg, SBP decrease by at least 40 mm Hg, or orthostatic blood pressu…

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Shock Syndromes II iv. Recommendations in a life-threatening hemorrhage: (a) Phytonadione 10 mg intravenously and a 4F-PCC (dose is determined by patient weight and pretreatment INR; see Table 7) a…

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Shock Syndromes II e. Dabigatran reversal: Idarucizumab is FDA approved for dabigatran reversal. i. Idarucizumab is a monoclonal antibody that binds both bound and unbound dabigatran. It has a bind…

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Shock Syndromes II v. Anticipated limitations when using andexanet in clinical practice: (a) The largest limitation of the ANNEXA-4 trial is the lack of a control group, with little ability to dete…

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Shock Syndromes II viii. Andexanet alfa dosing is complex (Table 7) and individualized according to the underlying anticoagulant and time from last dose. For example, rivaroxaban achieves higher ser…

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Data Tables 3 min

Shock Syndromes II Table 7. Anticoagulant Reversal Agent Dosing in Life-Threatening Hemorrhage Which Anticoagulant Reversal Agent Dose Warfarin with elevated INR 4F-PCC INR 2 to < 4: 25 units/kg (max…

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Data Tables 3 min

Shock Syndromes II 4. Desmopressin enhances platelet adherence and aggregation. a. Although its clinical efficacy is controversial, desmopressin 0.3–0.4 mcg/kg intravenously may be considered to re…

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Shock Syndromes II Patient Cases 5. A 54-year-old man with an unknown medical history presents after a rollover automobile accident. On pri- mary survey, his respiratory rate is 34 breaths/minute, SB…

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Shock Syndromes II a. In impaired diastolic filling, RV preload is significantly decreased because of the inhibition of venous return. i. In cardiac tamponade, an accumulation of fluid in the peric…

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Shock Syndromes II b. Impaired systolic function (massive PE): Embolism dissolution (thrombolytic therapy) or removal (surgical or catheter thrombectomy) i. Thrombolytic agents (Table 9) bind to th…

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Shock Syndromes II (3) Persistent hypotension (SBP less than 90 mm Hg or SBP decrease of 40 mm Hg or greater for more than 15 minutes, not caused by new-onset arrhythmia, hypovolemia, or sepsis) (b…

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Shock Syndromes II (c) A 2012 analysis of a National Inpatient Sample containing over 70,000 patients with an unstable PE (defined as the presence of shock or a requirement for mechanical ventilatio…

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Shock Syndromes II (b) Commonly used bleeding scores such as HAS-BLED moderately predict the risk of an intracranial hemorrhage after thrombolytic agents for PE but lack precision. HAS-BLED has not…

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Shock Syndromes II x. Catheter-directed thrombolysis (CDT) is an emerging treatment that enables the administration of lower-dose thrombolytic agents directly into the thrombus. (a) CDT has the adv…

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Shock Syndromes II 1. The authors reported that Black patients were 13% less likely to receive advanced PE therapy (thrombolysis, catheter-directed treatment, surgical embolectomy, or extracorporeal…

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Shock Syndromes II III.  STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS A. Epidemiology 1. Severe cutaneous reactions and related syndromes are unpredictable and rare. The primary causes o…

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Shock Syndromes II C. Etiology 1. Drugs are the most common cause of SJS and TEN and are implicated in more than 90% to 95% of cases. More than 200 medications have been reported as causing SJS and…

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Shock Syndromes II c. Mortality prediction increases sharply with each additional point, starting at 3% for 0 or 1 point and reaching 90% for 5 or more points. SCORTEN mortality estimates are often…

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Shock Syndromes II b. Immunomodulating therapy i. Corticosteroids—Despite some evidence of benefit, use is controversial and not universally recommended. More recent case reports suggest that high-…

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Shock Syndromes II ii. Cyclosporine—Information from individual case series suggests benefit at a dose of 3 mg/kg/d. There are no formal recommendations for routine use. iii. Cyclophosphamide—Early…

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Shock Syndromes II (h) The decision to administer IVIG remains clinically supported by pathophysiology- pharmacology interactions and observational data. Centers with expertise to care for patients…

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Shock Syndromes II REFERENCES Hypovolemic Shock Alvarado R, Chung KK, Cancio LC, Wolf SE. Burn resuscitation. Burns. 2009;35(1):4-14. https://doi. org/10.1016/j.burns.2008.03.008 American College o…

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Shock Syndromes II Franchini M, Lippi G. Prothrombin complex concen- trates: an update. Blood Transfus. 2010;8(3):149-154. https://doi.org/10.2450/2010.0149-09 Fröhlich M, Mutschler M, Caspers M, et…

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Shock Syndromes II Madsen TE, Simmons J, Choo EK, Portelli D, McGregor AJ, Napoli AM. The DISPARITY study: do gender dif- ferences exist in Surviving Sepsis Campaign resuscitation bundle completion,…

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Shock Syndromes II Sihler KC, Napolitano LM. Complications of massive transfusion. Chest. 2010;137(1):209-220. https://doi. org/10.1378/chest.09-0252 Sims CA, Holena D, Kim P, et al. Effect of low-do…

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Shock Syndromes II Circulation. 2011;123(16):1788-1830. https://doi. org/10.1161/cir.0b013e318214914f Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Th…

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Shock Syndromes II at disease onset. Am J Ophthalmol. 2009;147(6):1004- 1011.e1. https://doi.org/10.1016/j.ajo.2008.12.040 Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical…

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Answers & Explanations 4 min

Shock Syndromes II ANSWERS AND EXPLANATIONS TO PATIENT CASES 1. Answer: D This patient has class II hemorrhagic shock caused by penetrating trauma (heart rate greater than 100 beats/ minute, respira…

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Shock Syndromes II A normal TEG and elevated aPTT may not rule out the presence of dabigatran. In addition, it seems the patient took the last dabigatran dose within the previous 12 hours. Therefor…

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Shock Syndromes II data for the role of IVIG in SJS (Answer A is incorrect). Given the limited evidence supporting pharmacothera- peutic interventions and the life-threatening severity of TEN, burn…

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Self-Assessment 4 min

Shock Syndromes II ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS 1. Answer: C This patient presents with likely hemorrhagic shock after blunt trauma. The extent of injuries in highly vas- cu…

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Shock Syndromes II of fluid overload complications are greater with plasma (Answer B is correct). 5. Answer: A The patient has a massive PE, as evidenced by pulseless activity. Massive PE should be…

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