blood flow, intracellular oxygen, or cofactor availability. Antibiotics are usually categorized as having either concentration‐dependent or time‐dependent killing. The activity of concentration‐dependent antibiotics increases as the peak serum concentrations of drug increase. Time‐dependent antibiotics kill at the same rate regardless of the peak serum concentration that is attained above the MIC (minimum inhibitory concentration). Thus, an increase in dose is not associated with improved AUIC (area under the inhibitory concentration curve). Instead, increasing dosing frequency would improve antibiotic killing (Answer D). Decreases in renal function will prolong the half‐life of drugs eliminated by the kidneys (Answer E).Answer: BVarghese JA, Robert JA, Lipman J . Pharmacokinetics and pharmacodynamics in critically ill patients. Curr Opinion Anesth. 2010; 23 (4):472–478.Devlin JW, Barletta JF . Principles of drug dosing in critically ill patients . In Critical Care Medicine Parrillo JE and Dellinger RP (eds), 3rd edn, Mosby, Philadelphia, PA, 2008; pp. 343–76.9 Which statement is true regarding andexanet alfa, the factor Xa inhibitor reversal agent?Reverses only direct‐acting oral anticoagulants (DOACs) and not low‐molecular‐weight heparin.There is concern for prothrombotic effects post‐administration.It is a monoclonal antibody that binds to factor Xa.It has a long half‐life and rarely requires redosing.Dosing is based on the anticoagulant and the time from last dose.Andexanet alfa is a modified factor Xa protein (not a monoclonal antibody ‐ Answer C) that directly binds to the factor Xa inhibitors in a 1:1 ratio to inactivate their anticoagulant response. Due to structural modifications, it does not have a direct prothrombotic effect (Answer B). Andexanet alpha reverses both direct‐ (DOACs) and indirect‐ (low‐molecular‐weight heparin) acting anticoagulants (Answer A). It has a short half‐life of 1 hour and the infusion runs over 2 hours. In theory, the 2‐hour time interval allows for a hemostatic plug to form and bleeding to stop. A rebound anticoagulation effect has yet to be found. In early studies, nearly 80% of patients had good or excellent hemostasis at 12 hours and did not require re‐administration of andexanet alpha (Answer D). Andexanet alpha administration is based on the half‐life of the anti‐Xa inhibitor as well as when it was last taken. See chart below for dosing:AnticoagulantLast dose<10 mg: low doseRivaroxaban>10 mg within 8 hours: high dose>10mg after 8 hours: low dose<5 mg: low doseApixaban>5 mg within 8 hours: high dose>5 mg after 8 hours: low doseEnoxaparinHigh dose at any time(off‐label)Andexanet dosingLow dose400 mg bolus, 4 mg/min for 120 minHigh dose800 mg bolus and 8 mg/min for 120 minIf unsure time of last dose, assume high doseAnswer: EConnolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet Alfa for acute major bleeding associated with factor Xa inhibitors. ANNEXA‐4 investigators. N Engl J Med. 2016; 375 (12):1131–41.
10 Which of these antipsychotics is matched with its proper description?Haloperidol: atypical antipsychotic, fast onset, risk of QT interval prolongation, especially with IV formulation.Olanzapine: atypical antipsychotic, renally cleared, risk of severe anticholinergic effects.Quetiapine: atypical antipsychotic, hepatically cleared, risk of severe orthostatic hypotension.Risperidone: typical antipsychotic, fast onset, risk of Parkinsonism.Aripiprazole: atypical antipsychotic, slow onset, risk of QT interval prolongation.Olanzapine (Answer B), quetiapine (Answer C), and risperidone (Answer D) are atypical antipsychotics that are antagonists against D2, serotonin, histamine, and alpha‐2 receptors. Due to action on multiple receptors, the risk of extrapyramidal symptoms is less compared to haloperidol, but each have an increased risk of orthostatic hypotension. Haloperidol (Answer A) is a typical antipsychotic, which is a potent antagonist of the dopamine D2 receptor. Haloperidol has the strongest evidence for use in delirium and is available in oral (po), intramuscular (IM), and intravenous (IV) formulations. The IV form may cause QT interval prolongation. It also has minimal effects on vital signs and minimal interactions with other drugs. It has a moderate onset of action. All the antipsychotics are hepatically cleared. Olanzapine is the only atypical antipsychotic available in both IM and PO forms. Quetiapine has a high risk of orthostatic hypotension and is not recommended in emergency room settings for agitation. However, quetiapine is recommended for patients with Parkinson’s disease because it has little or no risk compared to the other atypical antipsychotics. Aripiprazole (Answer E) is a partial dopamine agonist. It is available in oral, dissolvable, and IM forms. While it may be less effective compared to other antipsychotics, it is also less sedating and does not have any effect on QT interval prolongation.Antipsychotic agentsAgentFormHalf‐life (hrs)ClearanceAdverse effectsEffect on QTOrthostatic hypotensionAntichol. effectsSedationConsiderationsHaloperidolPO, IM, IV12–38HepaticAkathisia, dystonia, ParkinsonismIV: moderateMildMildMildMinimal vital sign change, may worsen Parkinson’sOlanzapinePO, SL, IM21–54HepaticAkathisia, ParkinsonismMildModerateSevereModerateCancer‐related nausea, do not combine with IV benzos, may worsen diabetesQuetiapinePO6HepaticAgitationMildSevereModerateSevereConsider in Parkinson’s diseaseRisperidonePO, SL20HepaticParkinsonismMildSevereMildModerateComes in dissolvable formAripiprazolePO, SL, IM75HepaticAkathisia, agitationNoneModerateMildModerateHypoactive delirium, no known QTC effectAnswer: CThom RP, Mock CK, Teslyar P . Delirium in hospitalized patients: risks and benefits of antipsychotics. Cleve Clin J Med. 2017; 84 (8):616–622.
11 A 27‐year‐old man weighing 80 kg and otherwise healthy, presents with multiple gunshot wounds to the right thigh. There is no pulse distal to the injury and an expanding hematoma is present. He is taken urgently to operating room and is found to have 3 cm disruption of the superficial femoral artery at the mid‐thigh. Proximal and distal control are achieved, saphenous vein graft is harvested from the contralateral groin, four‐compartment fasciotomies are completed in the calf, and an end‐to‐end anastomosis is performed. Prior to performing the anastomosis, the patient is given 8000 units of heparin IV. Ninety minutes later, the patient has a palpable dorsalis pedis (DP) pulse; however, the fasciotomy sites and right groin are oozing considerably. How much protamine should be given to completely reverse the heparin?Protamine 12.5 mg IVProtamine 25 mg IMProtamine 40 mg IVProtamine 50 mg IMProtamine 80 mg IVProtamine sulfate completely reverses the action of unfractionated heparin. Protamine is a highly cationic peptide that binds heparin or low‐molecular‐weight heparin to form a stable ionic pair. The ionic complex is then removed and broken down by the reticuloendothelial system (RES). Approximately 1 mg of protamine sulfate neutralizes 100 units of heparin. The half‐life of heparin is about 60–90 minutes. Assuming normal renal function, there would be about 4000 units of heparin remaining in this patient (1 half‐life), which would require 40mg of IV protamine for complete reversal. Protamine can only be dosed IV and the maximum dose is 50 mg.Answer: CDhakal P, Rayamajhi S, Verma V, et al. Reversal of anticoagulation and management of bleeding in patients on anticoagulants. Clin Appl Thromb Hemost. 2017; 23 (5):410–415.
12 Which of these patients is most likely to develop propofol infusion syndrome?A 23‐year‐old man receiving propofol 50 mcg/kg/min for 6 hours due to a subdural hematoma and intraparenchymal hemorrhage.A 65‐year‐old woman receiving propofol 20 mcg/kg/min and norepinephrine 5 mcg/min for 24 hours following debridement for necrotizing fasciitis.A 45‐year‐old man receiving propofol 60 mcg/kg/min and norepinephrine 10 mcg/min for 60 hours for alcohol induced necrotizing pancreatitis.A 30‐year‐old woman receiving propofol 50 mcg/kg/min for 12 hours due to sustaining a subdural hematoma and following an exploratory laparotomy for splenectomy.A 75‐year‐old man receiving propofol 30 mcg/kg/min for 8 hours following a Whipple procedure and inability to extubate due to COPD.Propofol infusion syndrome is a rare syndrome characterized by cardiac arrhythmias and rhabdomyolysis, which can manifest with elevated creatine phosphokinase (CPK) and potassium, lactic acidosis, and renal failure. The most significant risk factor for development of propofol infusion syndrome is high‐dose propofol use for > 48 hours. Other risk factors include sepsis, head trauma, and status epilepticus. In addition, the use of vasopressors, glucocorticoids, mitochondrial disease, and carbohydrate depletion as seen with liver disease, starvation, or malnutrition can cause propofol infusion syndrome. Patient C is the only patient that received high‐dose propofol for > 48 hours. He is also septic, receiving vasopressors, and likely has some element of liver disease given his alcohol use.Answer: CMirrakhimov AE, Voore P, Halytskyy O, et al. Propofol infusion syndrome in adults: a clinical update. Crit Care Res Pract. 2015; 2015 :260385.
13 Which of the following antiemetic medications is matched with its correct description?Ondansetron:
