Читать книгу Surgical Critical Care and Emergency Surgery - Группа авторов - Страница 17

Michelle Strong, MD, PhD1 and Elaine Cleveland, MD2

1 Trauma and Acute Care Surgeon, Austin, TX, USA

2 William Beaumont Army Medical Center, El Paso, TX, USA

1 A 64‐year‐old man with a past medical history notable of hypertension, hyperlipidemia, peripheral vascular disease, and diabetes presents with copious purulent drainage coming from his right trans‐metatarsal amputation site. He has been spiking fevers for the last two days; his white blood cell count is 24 000, and his blood pressure is 95/40 mm Hg. Previous cultures at the time of his amputation 3 months ago grew extended spectrum beta‐lactamase (ESBL) Enterobacteriacea. What antibiotic should you start this patient on (assuming normal renal function)?Ampicillin/sulbactam 3 gm every 6 hrsCeftriaxone 1gm every 24 hrsPiperacillin/tazobactam 4.5 every 8 hrs (extended infusion)Cefepime 2 gm every 12 hrsMeropenem 1 gm every 8 hrsESBLs are plasmid‐mediated enzymes that inactivate all β‐lactam antibiotics including penicillins, third‐ and fourth‐generation cephalosporins (ceftriaxone and cefepime, respectively), and monobactams. Carbapenems and cephamycin are effective against ESBLs. Detection of ESBLs is often difficult and some microbiology laboratories do not employ reliable methods, which may result in false susceptible reporting of ESBL strains to cefotaxime, ceftazidime, and ceftriaxone. Cefepime, a fourth‐generation cephalosporin, does not appear to induce this type of chromosomal‐mediated resistance to the same degree as ceftazidime, but is susceptible to the action of ESBLs. Most ESBLs also co‐express resistance to other agents including aminoglycosides and fluoroquinolones. Carbapenems (specifically meropenem) are the most effective agents against ESBLs. An ESBL E‐test should be performed for this isolate, and the patient should be started on meropenem.Answer: EGhafourian S, Sadeghifard N, Soheili S, et al. Extended spectrum Beta‐lactamases: definition, classification and epidemiology. Curr Issues Mol Biol. 2015; 17 :11–21. Epub 2014 May 12.Nathisuwan S, Burgess DS, Lewis JS . Extended‐spectrum beta‐lactamases: epidemiology, detection, and treatment. Pharmacotherapy. 2001; 21 (8):920–928. PMID: 11718498McDaniel J, Schweizer M, Crabb V, et al. Incidence of Extended‐Spectrum β‐Lactamase (ESBL)‐ producing Escherichia coli and Klebsiella Infections in the United States: a systematic literature review. Infect Control Hosp Epidemiol. 2017; 38 (10):1209–1215. PMID: 28758612

2 A 76‐year‐old woman with end‐stage renal disease, uncontrolled diabetes, and pain control issues has been admitted to the ICU after undergoing an open right hemicolectomy. The procedure was uncomplicated, and the patient was extubated 3 hours after admission to the surgical intensive care unit. On examination, there is a nasogastric tube in place, and her vital signs are BP 110/60 mmHg, HR 85 beats/min, RR is 20 breaths/min, pulse oximetry 94% on 2L oxygen via nasal cannula, and she rates her pain on a 0–10 scale as 6.Which one of the following analgesics for postoperative pain management is the best choice for this patient?TramadolOfirmevOxycodoneMorphineCelebrexAcetaminophen injection (Ofirmev®) is indicated for the management of mild‐to‐moderate pain and as an adjunct to opioid analgesics and other agents. Acetaminophen in metabolized by the liver and does not require adjustment in end‐stage renal disease (ESRD). Patients report better pain control than with oral acetaminophen. Tramadol is metabolized to an active metabolite O‐demethyl tramadol, which is excreted by the kidneys. Its elimination half‐life is prolonged 2 times in patients with decreased glomerular filtration rate (GFR). Tramadol may be epileptogenic, especially with associated conditions that lower seizure threshold, such as with uremia. Respiratory depression is also described in patients with chronic kidney disease. Morphine should be used cautiously as morphine metabolites can accumulate, increasing therapeutic and adverse effects in patients with renal failure. Morphine and its metabolite can be removed with dialysis. Oxycodone should not be used in patients with renal failure. Oxycodone and its metabolites can accumulate causing toxic and CNS‐depressant effects. There is no data on oxycodone and its metabolites removal with dialysis; however, oxycodone’s half‐life is significantly prolonged in ESRD. Celebrex is a nonsteroidal anti‐inflammatory drug (NSAIDs), specifically a COX2 inhibitor, used to treat pain and inflammation. NSAIDs may lead to reversible reduction in GFR. COX2 is constitutively expressed in the kidney and has an important role in maintaining renal hemodynamics. Although potentially advantageous for patients at risk of bleeding, COX2 inhibitors appear to exert similar effects on the kidney compared with traditional NSAIDs.Answer: BDavison SN . Pain in hemodialysis patients: prevalence, cause, severity, and management. Am J Kid Dis. 2003; 42 : 1239–1247.Foral PA, Ineck JR, Nystrom KK . Oxycodone accumulation in a hemodialysis patient. South Med Journal. 2007; 100 : 212–214.Kurella M . Analgesia in patients with ESRD: a review of available evidence. Am J Kid Dis. 2003; 42 : 217–228.Golembiewski J Intravenous acetaminophen. J. Perianesth Nurs. 2017; 32 (2):151–55.

3 A 36‐year‐old man is involved in high‐speed motor vehicle collision and was intubated in the field for a Glasgow Coma Scale (GCS) score of 4. His injuries include a severe traumatic brain injury with multiple intraparenchymal and intraventricular hemorrhages, multiple rib fractures bilaterally, bilateral pulmonary contusions, and a right femur fracture that is now in traction. Due to elevated intracranial pressures that have not been controlled, the patient is placed on a cisatracurium drip. Which statement is true regarding cisatracurium?Primarily renally cleared.Cheaper cost compared to vecuronium.Is an aminosteroid‐based neuromuscular blocking agent, similar to rocuronium.Associated with better outcomes in acute respiratory distress and traumatic brain injury.Fast onset of action and used for emergency airway management.Cisatracurium is a widely used nondepolarizing neuromuscular blocking agent (NMBA). Cisatracurium, an isomer of atracurium, undergoes spontaneous chemical degradation (not an enzymatic process) in a process known as Hofmann elimination. The cost of cisatracurium is substantially higher compared to other NMBA. Other NMBAs like pancuronium, rocuronium, and vecuronium are aminosteroid based and their elimination can be affected by hepatic or renal dysfunction. There are three randomized trials that have shown improvement with oxygenation in ARDS patients using cisatracurium. Two additional randomized trials found no decrease in intracranial pressure, mean arterial pressure, cerebral perfusion pressure, or cerebral blood flow velocity with cisatracurium. With atracurium, these parameters decreased and a subsequent rebound in elevated intracranial pressure was noted. Cisatracurium has a relatively slow onset, and should not be used for emergency airway management. Cisatracurium is often the paralytic of choice in patients with severe hepatic and renal dysfunction. Hofmann elimination is a temperature‐ and pH‐dependent process, and therefore the rate of degradation is highly influenced by body pH and temperature; an increase in body pH favors the elimination process, whereas a decrease in temperature slows down the process.Answer: DSzakmany T, Minerva WT . Use of cisatracurium in critical care: a review of the literature. Anestesiol. 2015; 81 (4):450–60. Epub 2014 Apr 10.Sparr HJ, Beaufort TM, Fuchs‐Buder T . Newer neuromuscular blocking agents: how they compare with established agents? Drugs. 2001; 61 :919–942.

4 A 37‐year‐old man is involved in an all‐terrain vehicle (ATV) collision and has multiple left rib fractures, a left humerus fracture, and a grade II splenic laceration. Prior to his crash, he was taking alprazolam 2 mg three times a day. On post‐trauma day 3, the patient is restless, shaking, tachycardic, diaphoretic, and having auditory hallucinations. Which is true regarding alprazolam withdrawal?Alprazolam withdrawal is typically less severe compared to other benzodiazepines.Due to the long half‐life, the abuse potential is lower compared to other benzodiazepines.Alprazolam has a slow absorption and high lipophilicity.Alprazolam uniquely affects dopaminergic function in the brain.Rebound anxiety is more commonly seen with diazepam withdrawal than with alprazolam withdrawal.Alprazolam has a high misuse potential and more severe withdrawal symptoms compared to other benzodiazepines. Alprazolam has unique pharmacokinetic properties since it is less protein‐bound compared to other benzodiazepines resulting in rapid absorption, low lipophilicity, and short half‐life. The half‐life for alprazolam is 8–16 hours, while the half‐life of diazepam is 22–72 hours (assuming healthy adult). In addition, alprazolam does not accumulate oxidative metabolites. Diazepam and its metabolites accumulate in the body and after discontinuation, there is a slow washout leading to less severe withdrawal symptoms. Alprazolam also crosses the blood‐brain barrier and affects the dopaminergic function in the striatum leading to increased serotonin levels, thus, making it higher risk for abuse and misuse. Alprazolam withdrawal is more complicated and has a unique rebound anxiety associated with it.Answer: DAit‐Daoud N, Hamby AS, Sharma S, et al. A review of alprazolam use, misuse, and withdrawal. J Addict Med. 2018; 12 (1):4–10.

5 A 38‐year‐old woman was involved in motorcycle crash and sustains a small subdural hematoma, an intraparenchymal hemorrhage, multiple right‐sided rib fractures, right tibia and fibula fractures, and significant skin abrasions along right side of her body. She is intubated and sedated with dexmedetomidine drip in the ICU secondary to a Glasgow Coma Scale (GCS) score of 8. What is true regarding dexmedetomidine?It works on GABA receptors, like propofol.Side effects are mostly hemodynamic alterations such as hypotension, bradycardia, and hypertension.It is mainly eliminated via the kidneys and abnormal renal function can affect elimination.It has a long half‐life, usually about 12 hours in healthy adults.In the ICU, it can be used for deep sedation and with paralytics.Dexmedetomidine is a selective α2 adrenoceptor agonist that is used for its anxiolytic, sedative, and analgesic properties. Propofol and benzodiazepines both act on GABA receptors (Answer A). The side effects of dexmedetomidine are mainly hemodynamic changes, to include hypotension, sometimes hypertension, and bradycardia (Answer B). It is mainly hepatically eliminated and elimination can be impacted by hypoalbuminemia and liver failure. The half‐life of dexmedetomidine is 2–3 hours in healthy adults and 2.2–3.7 hours in ICU patients (Answer D). It is approved for light to moderate sedation, not for deep sedation. It should not be used with paralytics in the ICU as it does not provide adequate sedation and cannot achieve the Richmond Agitation Sedation Score (RASS) of ‐4 or ‐5 that is recommended for paralytics (Answer E).Answer: BWeerink MAS, Struys MMRF, Hannivoort LN, et al. Clinical pharma‐cokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 2017; 56 (8):893–913.Oddo M, Crippa IA, Mehta S, et al. Optimizing sedation in patients with acute brain injury. Crit Care. 2016; 20 (1):128.

6 A 63‐year‐old man weighing 110 kg has a history of multiple pulmonary embolisms and is currently receiving warfarin therapy, presents with 3 hours of hematemesis. His vital signs are BP 86/45 mmHg, HR 121 beats/min, RR 22 breaths/min, and his temperature is 98.9°F. A nasogastric tube is placed with a large amount of bright red blood returned. His hemoglobin is 5.2 g/dL and his INR is 9.2. What is the most effective immediate reversal of his warfarin?Phytonadione 10 mg orally once.Four‐factor prothrombin complex concentrate (PCC) 50 units/kg IV infused over 30 min.Tranexamic acid 1 gm IV over 10 minutes and followed by 1 gm IV over 8 hours.Fresh frozen plasma 15 mL/kg and repeat if INR > 3 on post‐transfusion laboratory.Phytonadione 10 mg IV infusion daily for three days.This patient has an acute gastrointestinal hemorrhage complicated by supratherapeutic warfarin and hemodynamic instability. Reversal should be with four‐factor PCC (Kcentra). Four‐factor PCC contains factors IIa, VIIa, IXa, and Xa; proteins C, S, and Z; antithrombin III; and a small amount of heparin. Because of the heparin in the preparation, a patient with a history of heparin‐induced thrombocytopenia, or an allergy to heparin, should not receive four‐factor PCC (Kcentra). However, patients can receive activated four‐factor PCC (FEIBA). Given his weight and elevated INR (INR > 6), the dose should be 50 units/kg, not to exceed 5000 units. For an INR 2–4, the dose should be 25 units/kg, not to exceed 2500 units; and for INR 4–6, the dose should be 35 units/kg, not to exceed 3500 units. While phytonadione (vitamin K) should be given intravenously (not orally ‐ Answer A), the onset is 6–12 hours, and would not rapidly reverse this patient’s severe supratherapeutic INR. Fresh frozen plasma requires large volumes, often has incomplete INR correction, has a risk of transfusion‐related reactions, and requires extended time to achieve hemostasis, and therefore would not be ideal for a hemodynamically unstable patient. While tranexamic acid, an antifibrinolytic agent, has been shown to be beneficial in trauma and obstetric hemorrhage in studies such as CRASH 2 and WOMAN trial, respectively, it should not be used for warfarin reversal.Answer: BDaley, MJ, Bauer, SR. Shock Syndromes II: hypovolemic, critical bleeding, and obstructive. 2019 ACCP Critical Care Pharmacy Preparatory Review and recertification Course. 2019

7 Which of the following patients would be most appropriate for alvimopan?A 46‐year‐old man with hypertension and hyperlipidemia who is scheduled to undergo a laparoscopic colostomy reversal with colorectal anastomosis.A 63‐year‐old man with end‐stage renal disease on dialysis and diabetes who is scheduled to undergo a sigmoid resection for cancer.A 55‐year‐old woman with chronic back pain who is currently taking 15 mg morphine equivalents daily and is scheduled to have a laparoscopic gastric bypass.A 36‐year‐old woman who is postoperative day 4 following a small bowel resection secondary to a small bowel obstruction and has a persistent ileus.A 68‐year‐old man with COPD who is postoperative day 3 following a right hemicolectomy for cancer with end ileostomy and is now having 1500 mL/day output from his nasogastric tube.Alvimopan is a selective peripherally acting μ‐opioid receptor antagonist that specifically targets peripheral μ receptors in the GI tract. It is used to accelerate time to upper and lower gastrointestinal (GI) recovery following large or small bowel resection surgery in patients who undergo a primary anastomosis. Alvimopan blocks the adverse effects of opioids on the GI tract without affecting overall analgesia. It has been shown to reduce time to GI transit and subsequently reduce hospital time. Alvimopan is indicated for planned inpatient surgery in patients undergoing partial bowel resection with primary anastomosis. Ideal dosing is a single 12 mg capsule 30 minutes to 5 hours prior to surgery, and then subsequent twice daily dosing beginning on postoperative day 1, for a maximum of 7 days (15 doses) or until discharge. Patients must remain inpatient while taking alvimopan. Alvimopan is contraindicated in patients who have received therapeutic dosing of opioids for more than 7 days prior to surgery, have severe hepatic impairment, or end‐stage renal disease. It should not be used in patients with a small bowel obstruction or in those patients who will not undergo a primary anastomosis. Patient B is not a candidate due to end‐stage renal disease. Patient C is not a candidate due to chronic high‐dose opioid usage prior to surgery. Patient D is incorrect since she is postoperative from small bowel obstruction with a persistent ileus. Patient E is incorrect because he is postoperative, did not have a primary anastomosis, and is having high‐volume nasogastric tube output.Answer: ACurran MP, Robins GW, Scott LJ, et al. Alvimopan. Drugs. 2008; 68 (14):2011–9.Xu, LL, Zhou XQ, Yi PS, et al. Alvimopan combined with enhanced recovery strategy for managing postoperative ileus after open abdominal surgery: a systematic review and meta‐analysis. J Surg Res. 2016; 203 :211–221.Vaughan‐Shaw PG, Fecher IC, Harris S, et al. A meta‐analysis of the effectiveness of the opioid receptor antagonist alvimopan in reducing hospital length of stay and time of GI recovery in patients enrolled in a standardized accelerated recovery program after abdominal surgery. Diseases Colon and Rectum. 2012; 55 :611–620.

8 Which one of the following definitions of pharmacokinetic and pharmacodynamic principles in the critically ill patient is correct?Aggressive fluid resuscitation will not alter the volume of distribution in morbidly obese patients.Metabolic clearance by the liver, mostly via the cytochrome P450 system, may be compromised in the critically ill patient by decreases in hepatic blood flow, intracellular oxygen tension, and cofactor availability.Gut wall edema, changes in gastric or intestinal blood flow, concurrent administration of enteral nutrition, and incomplete oral medication dissolution has no effect on drug absorption. The response to antibiotics that have time‐dependent killing pharmacodynamics would be improved by administering a higher dose of drug to increase the area under the inhibitory curve.Deceased in renal function decreases the half‐life of medications cleared via the kidney and result in accumulation of drugs or their metabolites.Critically ill patients have alterations in medication pharmacokinetics and pharmacodynamics. Pharmacokinetics characterizes what the body does to a drug—the absorption, distribution, metabolism, and elimination of the drug. Pharmacodynamics is what the drug does to the body and describes the relationship between the concentration of drug at the site of action and the clinical response observed. Many factors affect drug absorption, distribution, and clearance in the critically ill patient. Failure to recognize these variations may result in unpredictable serum concentrations that may lead to therapeutic failure or drug toxicity. Drug absorption is altered by gut wall edema and stasis, changes in gastric and intestinal blood flow, concurrent medications and therapies such as enteral nutrition, and incomplete disintegration or dissolution of oral medications (Answer C). The volume of distribution describes the relationship between the amount of drug in the body and concentration in the plasma. Fluid shifts, particularly after fluid resuscitation, and protein binding changes that occur during critical illness, alter drug distribution (Answer A). Plasma protein concentrations may change significantly during critical illness and may affect the volume of distribution by altering the amount of the active unbound or free drug. Metabolic clearance by the liver is the predominant route of drug detoxification and elimination. With hepatic dysfunction that may occur in the critically ill patient, drug clearance may be decreased secondary to reduced hepatic blood flow, decreased hepatocellular enzyme activity, or decreased bile flow. A common pathway for drug metabolism is the cytochrome P450 system (Answer B). Critical illness may compromise this system by decreasing hepatic 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: serotonin antagonist; adverse effects: headache, constipation.Dexamethasone: corticosteroid; adverse effects: dry eyes, hypotension.Promethazine: serotonin antagonist; adverse effects: sedation, dizziness.Scopolamine: dopamine antagonist; adverse effects: dizziness, dry mouth.Metoclopramide: dopamine antagonist; adverse effects: hyperglycemia, hypertension.Postoperative nausea and vomiting (PONV) is a common complication following surgery. As more procedures transition to outpatient surgery and enhanced recovery protocols try to minimize hospital stays, the management of postoperative nausea and vomiting becomes more important. Besides antiemetics, other strategies to reduce PONV include local nerve blocks, propofol induction and maintenance, minimizing perioperative narcotics, minimizing volatile anesthetics, avoiding nitrous oxide and reversal agents, and providing adequate perioperative hydration. Ondansetron is a serotonin antagonist and is usually well tolerated, though can cause headaches and constipation. Dexamethasone is a corticosteroid and can cause hyperglycemia and hypertension or hypotension. Promethazine is a histamine (H1) antagonist and causes sedation and dizziness. Scopolamine is an anticholinergic which causes dry mouth, visual disturbances, and dizziness. Metoclopramide is dopamine antagonist which can cause sedation and hypotension.AntiemeticsDrug groupDrugsDoseTiming for PONVAdverse effectsSerotonin (5‐HT3 receptors) antagonistsOndansetron4–8 mg IVGranisetron1 mg IVEnd of surgeryHeadaches, constipation, raised LFTsTropisetron2 mg IVCorticosteroidsDexamethasone4–10 mg IVAfter anesthesia inductionIncreased glucose, hypo/hypertensionButyrophenoneDroperidol0.625 to 1.25 mg IVAfter anesthesia inductionExtrapyramidal disturbances, Parkinson’s, increased QTNeurokinin antagonists (NK‐1 receptors)Aprepitant40 mg PO1–2 hour pre‐opHeadaches, constipation, fatigueAnticholinergicsScopolaminePatchPre‐opDizziness, dry mouth, visualDopamine antagonistsMetoclopramide10–25mg IV15 min prior to end of surgerySedation, hypotension1st generation AntihistaminePromethazine12.5 to 25 mg PO/IM/IVPost‐opSedation, dizziness, extrapyramidal disturbancesAnswer: ACao X, White PF, Ma H . An update on the management of postoperative nausea and vomiting. J Anesth. 2017; 31 (4):617–626.

14 A 76‐year‐old man with hypertension, peripheral vascular disease, and diabetes is taking warfarin for atrial fibrillation. He also had a stroke 2 years ago. He will be undergoing a robotic low anterior resection for rectal cancer. What should be the management of his warfarin?Stop warfarin 5 days prior to surgery, resume postoperative (POD) 2.Stop warfarin 5 days prior to surgery, start weight‐based enoxaparin 3 days prior to surgery, stop enoxaparin day of surgery, resume warfarin POD 1.Stop warfarin 5 days prior to surgery, start weight‐based enoxaparin 3 days prior to surgery, stop enoxaparin day before surgery, resume warfarin POD 1.Stop warfarin 3 days prior to surgery, start weight‐based enoxaparin 3 days prior to surgery, stop enoxaparin day before surgery, resume warfarin POD 2.Stop warfarin 3 days prior to surgery, start weight‐based enoxaparin 3 days prior to surgery, stop enoxaparin day before surgery, resume warfarin POD 5.Stopping anticoagulation medication prior to surgery must be weighed against the risk of thromboembolic events and the surgical bleeding risk. This patient has a high CHA2DS2‐VASc score of 7 (hypertension ‐1, age > 75 ‐ 2, diabetes ‐1, stroke ‐2, and vascular disease ‐1) and is high risk for thromboembolic events, and therefore, should not have anticoagulation stopped completely (Answer A). This patient should be placed on enoxaparin therapy, which should be stopped the day before surgery (Answer C) and warfarin should be started POD 1, provided no/minimal bleeding risk. Weight‐based enoxaparin should also be restarted 12–24 hours after surgery depending on bleeding risk, as it will take multiple days for warfarin to reach therapeutic levels.BRIDGE trial anticoagulation protocolDay (around procedure)Protocol−5Stop warfarin−3Start bridging agent (LMWH)−1Stop bridging agent 24 hours prior to procedure0Procedure1Resume warfarin within 24 hours, resume bridging agent within 12 to 24 hours for low risk bleed2 to 3Resume bridging agent within 48–72 hours for high‐risk procedure5 to 10Stop bridging agent when INR > 2Answer: CBarnes GD, Mouland E . Peri‐procedural management of oral anticoagulants in the DOAC Era. Prog Cardiovasc Dis. 2018; 60 (6):600–606.

15 A 45‐year‐old woman pedestrian was struck by a motor vehicle. She has a history of COPD and a penicillin allergy. She sustained bilateral rib fractures with a flail segment on the left, left pulmonary contusion, left diaphragmatic injury (status‐post repair), and left open tibia and fibula fractures (also status‐post repair). She was admitted to the surgical ICU 8 days ago. She has been difficult to wean from the ventilator and has had a central line and left chest tube in place since admission. She began spiking fevers 2 days ago and is now requiring vasopressors. Empiric cefepime, metronidazole, and vancomycin were started, but clinically she has not improved. Her bronchoalveolar lavage (BAL) and blood cultures have come back positive for Candida with species pending. What is the best treatment choice for this patient currently?Continue current antibiotics and give more time to improveFluconazole 200 mg IV dailyVoriconazole 4 mg/kg IV dailyCaspofungin 70 mg IV x1 followed by 50 mg IV dailyFlucytosine 50 mg/kg IV q6 hoursEmpiric antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever. This patient is not improving and cultures indicate fungal bacteremia and ventilator‐associated pneumonia (VAP), thus, continuing the current antibiotic regimen would not treat this patient. Empiric antifungal therapy should be started as soon as possible in patients who have risk factors and who have clinical signs of septic shock. The preferred empiric therapy for suspected candidiasis in nonneutropenic patients in the ICU is an echinocandin (micafungin 100 mg IV daily, caspofungin 70 mg IV × 1 followed by 50 mg IV daily, anidulafungin 200 mg IV × 1 followed by 100 mg IV daily). Thus, Answer D is correct. Fluconazole at higher doses 800 mg IV ×1 followed by 400 mg IV daily is an acceptable alternative for patients who have not had recent azole exposure. B is incorrect because the dose is subtherapeutic. Voriconazole is used in much higher doses (6 mg/kg) BID × 2 then 3 mg/kg BID, but offers little advantage over fluconazole as initial therapy. Voriconazole is recommended as step‐down therapy for selected cases of candidemia due to Candida krusei, for additional mold coverage and for neutropenic patients. Flucytosine is usually used in combination with other antifungals and reserved for very severe infections. It is used more commonly in combination with amphotericin B for central nervous system candidiasis. In addition, higher doses (100–200 mg/kg) in 4 doses over 24 hours are recommended.Answer: DPappas PG, Kauffman CA, Andes AR, et. al. Clinical practice guidelines for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2016; 62 :e1–50.

16 A 63‐year‐old woman is receiving rivaroxaban following a pulmonary embolism she had 5 months ago. She also has hypertension and hyperlipidemia. She has normal renal function. She will be undergoing a mastectomy with sentinel lymph node biopsy for stage 2 ductal carcinoma. How should her rivaroxaban be managed in the perioperative period?Last dose of the DOAC prior to elective procedureAgentRenal clearanceLow bleed riskHigh or unknown bleed riskRivaroxaban, apixaban, edoxabanCrCl > 30 mL/min>24 hours>48 hoursCrCl 15–29 mL/min>36 hours>72 hoursCrCl < 15 mL/min>48 hoursData lackingDabigatranCrCl > 80 mL/min>24 hours>48 hoursCrCl 50–80 mL/min>36 hours>72 hoursCrCl 30–49 mL/min>48 hours>96 hoursCrCl 15–29 mL/min>72 hours>120 hoursCrCl < 15 mL/minUnknownUnknownStop rivaroxaban 5 days before surgery and restart POD 1.Stop rivaroxaban 2 days before surgery and restart POD 1.Stop rivaroxaban 5 days before surgery, start weight‐based enoxaparin, and restart POD 1.Stop rivaroxaban 2 days before surgery, start weight‐based enoxaparin, and restart POD 2.Stop rivaroxaban day of surgery and restart POD 2.This patient is at intermediate risk for thromboembolic events and should stop anticoagulation in the perioperative period without significant consequence. The direct‐acting oral anticoagulants (DOACs) rarely need bridging therapy (Answers C & D). Provided normal renal function, rivaroxaban should be eliminated entirely by 35–55 hours, since its half‐life is 7–11 hours (4–5 half‐lives for 95% elimination). A mastectomy has a higher risk of bleeding compared to some other surgeries, thus, rivaroxaban should be stopped 2 days prior to surgery and resumed POD 1 provided no bleeding complications.Answer: BBarnes GD, Mouland E . Peri‐procedural management of oral anticoagulants in the DOAC Era. Prog Cardiovasc Dis. 2018; 60 (6):600–606.

17 A 45‐year‐old man was involved in a high‐speed motor vehicle crash and has the following injuries: intraparenchymal hemorrhage, diffuse axonal injury, T4 vertebral body fracture, T4 paraplegia, and multiple bilateral rib fractures. On hospital day 9, the patient remains intubated, spikes a fever, and has thick secretions from the endotracheal tube. Subsequent bronchial alveolar lavage is performed, and the culture grows vancomycin‐ resistant enterococcus (VRE). Blood cultures also grow 2/2 bottles with VRE. Which is the best choice of antibiotic to use?CefepimeLinezolidDaptomycinPiperacillin‐tazobactamMeropenemVancomycin‐resistant enterococci (VRE) was first reported in 1986 and cases have been increasing in the ICU. In 2006 in the US, the rate of VRE was 0.6 per 1000 admissions. There is an increased risk of mortality with VRE bacteremia and treatment should be started promptly. Effective treatments for VRE include quinupristin‐dalfopristin, linezolid, daptomycin, tigecycline, teicoplanin, and telavancin. Linezolid and daptomycin are the two most commonly used antibiotics in the US for VRE. Linezolid (Answer B) is an oxazolidone that binds to the 50S ribosomal subunit, has been approved by the FDA for VRE treatment, has better tissue penetration than other antibiotics, especially lung penetration, and is bacteriostatic. Linezolid can suppress bone marrow, is expensive, and can interact with psychiatric medications, particularly monoamine oxidase inhibitors (MAOIs). Daptomycin (Answer C) is a novel cyclic lipopeptide that inhibits DNA and RNA synthesis and is bactericidal. It is not approved by FDA for VRE infections, though it is recognized as an appropriate treatment for some VRE infections; however, it should not be used to treat pneumonia because it is inactivated by alveolar surfactant. Daptomycin may cause Clostridium difficile, rhabdomyolysis, and thrombocytopenia. A meta‐analysis showed linezolid treatment for VRE bacteremia had a lower mortality compared to daptomycin. Cefepime, piperacillin‐tazobactam, and meropenem are not indicated for VRE.Answer: BPrematunge C, MacDougall C, Johnstone J, et al. VRE and VSE bacteremia outcomes in the Era of effective VRE therapy: a systematic review and meta‐analysis. Infect Control Hosp Epidemiol. 2016; 37 (1):26–35.Chuang Y‐C, Wang J‐T, Lin H‐Y,et al. Daptomycin versus linezolid for treatment of vancomycin‐resistant enterococcal bacteremia: systematic review and meta‐analysis. BMC Infectious Diseases. 2014; 14 :687–695.Kalil AC, et al Management of adults with hospital‐acquired and ventilator‐associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016; 63 (5):e61–e111. PMID: 27418577.

18 Which of the following is the best practice to prevent antibiotic resistance in the ICU?Initially treating a septic shock patient of unknown etiology with monotherapy quinolones.Continuing antibiotics for at least 7 days for intra‐abdominal sepsis after source control.Continuing vancomycin in a patient with ventilator‐associated pneumonia due to E. coli.De‐escalation of antibiotics based on culture results.Decrease the infusion time of intravenous antibiotics.Effective antimicrobial therapy is critical for the treatment of patients in the ICU and appropriate therapy decreases mortality as well as antibiotic resistance. The Surviving Sepsis campaign highlights starting antibiotics within an hour of emergency room admission or suspicion of sepsis and appropriate antimicrobial coverage of the suspected source. Sepsis of unknown origin requires active therapy against gram‐positive and gram‐negative pathogens. Common regimens are cefepime and vancomycin or piperacillin‐tazobactam and vancomycin. Quinolones only (Answer A) provide narrow coverage for gram‐negative bacteria and would not be appropriate for a septic patient of unknown origin. The Short Course Antimicrobial Therapy for Intraabdominal Infection (STOP‐IT) trial showed there was no difference in outcomes between 4 days and 8 days of antibiotics after source control had been achieved. Another study showed longer antibiotic courses led to increased risk of secondary infections and higher mortality. Answer B is incorrect because the patient only needs 4 days of antibiotics. It is important to de‐escalate antibiotics as soon as possible (Answer D). As vancomycin is used to cover gram‐positive bacteria, and specifically methicillin‐resistant Staph aureus (MRSA), vancomycin should be stopped as soon as it is known that the organism is not MRSA (Answer C). Answer E is incorrect because it is important to maintain minimum inhibitory concentration (MIC) of antibiotics. To achieve this, many beta‐lactamase antibiotics (cefepime, piperacillin) have been switched to extended infusions.Answer: DCampion M, Scully G . Antibiotic use in the intensive care unit: optimization and de‐escalation. J Intensive Care Med. 2018; 33 (12):647–655.

19 An 82‐year‐old man was started on clindamycin for left lower extremity cellulitis. Eight days after starting antibiotics, he presents to the emergency department with severe diarrhea, fever, abdominal pain, and emesis. His vitals are: HR 130 bpm, BP 90/50 mmHg, and his WBC is 35 000. C. difficile PCR is positive. What is the best management of his C. difficile infection?Discontinue antibiotics onlyDiscontinue antibiotics and start IV vancomycinDiscontinue antibiotics and start PO metronidazoleDiscontinue antibiotics and start PO vancomycinDiscontinue antibiotics and start IV rifampinClostridium difficile infection (CDI) has increased in frequency and severity over the last decade. Minimizing antibiotics, especially clindamycin and fluoroquinolones, is the cornerstone of prevention. This patient has severe C. difficile infection, as he presents in septic shock. Based on current treatment regimens, the previous antibiotics need to be stopped and vancomycin 125 mg orally four times a day should be started. Discontinuation of antibiotics only (Answer A) is incorrect as this patient needs additional treatment since he is in septic shock. Answer B is incorrect since vancomycin should be given via the oral (PO) route and not the IV route. Vancomycin administered IV does not reach therapeutic levels in the colonic lumen. Answer C is incorrect since oral metronidazole is only for mild disease or if oral vancomycin is unavailable or contraindicated. Metronidazole, administered either orally or IV, only reaches low therapeutic levels in the colon; therefore, even a slightly elevated MIC of C. difficile for metronidazole may lead to therapy failure. Multiple studies have shown that monotherapy of IV metronidazole is inferior to monotherapy PO vancomycin for treatment of Clostridium difficile. If the patient advances to fulminant colitis, the regimen would be vancomycin 500 mg orally or via nasogastric tube four times a day and metronidazole 500 mg intravenously every eight hours. Surgery would also be indicated with fulminant colitis. Rifampin (Answer E) is incorrect because while it has been used previously, data is lacking on its efficacy and is currently not recommended.Findoxamin, a novel macrolide antibiotic, bezlotoxumab, a monoclonocal antibody against toxin TCDB, and fecal microbiota transplant, are gaining popularity, especially in recurrent infections. Surgical treatment, typically a total colectomy, are reserved for those patients with fulminant colitis, though patient selection and timing of operation can be challenging.Answer: DGuh AY, Kutty PK . Clostridioides difficile infection. Ann Intern Med. 2018; 169 (7):ITC49–ITC64.Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of clostridium difficile‐ associated diarrhea in adults and children. The Cochrane Database of Systematic Reviews. 2017 Dec; 19(12):CD006095Bignardi GE . Risk factors for clostridium difficile infection. J Hosp Infect. 1998; 40(1):1–15. PMID: 9777516.Bowman JA, Uteer GH . Evolving strategies to manage clostridium difficile infections. J Gastrointest Surg. 2020; 24(2):484–91.

20 A 55‐year‐old otherwise healthy man presents to the emergency department with a large incarcerated umbilical hernia. He is brought to the operating room for open surgical repair. The patient was paralyzed with rocuronium to assist the reduction of the hernia. The surgery goes well and you tell the anesthesiologist that you are finished closing the fascia; however, a dose of rocuronium was just administered. Which statement is true regarding neuromuscular blocking agents (NMBAs) reversal?Neostigmine is an anticholinergic drug that is often used in conjunction with agents such as atropine and glycopyrrolate. The reversal agent available for succinylcholine is edrophonium.The mechanism of action of sugammadex includes chelating the NMBAs, making them inactive and removing them from the neuromuscular junction.Sugammadex is slower at reversing NMBA‐induced paralysis than both neostigmine and edrophonium.Acetylcholinesterase inhibitors are reversal agents available for depolarizing NMBAs.Neuromuscular blocking agents (NMBAs) can be broken down into two main classes: depolarizing and nondepolarizing agents. Succinylcholine is the only member of the depolarizing class of NMBAs and there is no reversal agent available (Answer B). The nondepolarizing NMBAs are rocuronium, pancuronium, vecuronium, atracurium, and its isomer, cisatracurium. Neostigmine and other acetylcholinesterase inhibitors (Answer A – incorrect choice because neostigmine is an acetylcholinesterase inhibitor) were the only reversal agents available for nondepolarizing NMBAs (Answer E). These agents increase the endogenous amount of acetylcholine available for binding at the neuromuscular junction, thus, competitively counteract the NMBAs effect. Sugammadex is a novel class of drugs called selective relaxant binding agents (SRBAs). The mechanism of action is twofold: (1) encapsulating (chelating) steroid backboned NMBAs (rocuronium, pancuronium, vecuronium) making them inactive and removing them from the neuromuscular junction, thus restoring muscle function; (2) the NMBAs that are already bound to nicotinic receptors will dissociate from the receptor (Answer C). Sugammadex exerts its effect by forming very tight complexes at a 1:1 ratio with aminosteroid muscle relaxants (rocuronium > vecuronium >> pancuronium). The intermolecular (van der Waals’) forces, thermodynamic (hydrogen) bonds and hydrophobic interactions make the sugammadex–rocuronium complex very tight. The resulting reduction in free‐rocuronium plasma concentration creates a gradient between the tissue compartment (including the neuromuscular junction) and plasma‐free rocuronium moves from tissue to plasma, with a reduction in nicotinic receptor occupancy at the neuromuscular junction. Multiple trials have found sugammadex is faster at reversing rocuronium‐ and vecuronium‐induced paralysis than both neostigmine and edrophonium (Answer D) while having similar adverse event profiles as the traditional cholinesterase inhibitors. Atropine and glycopyrrolate (Answer A) are both anticholinergic drugs that are often used in conjunction with cholinesterase inhibitors (neostigmine and edrophonium) to help offset their cholinergic effects such as bradycardia and excessive salivation. They have no role in NMBA reversal when used by themselves.Answer: CAbrishami A, Ho J, Wong J, et al. Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade. The Cochrane Library. 2009 Oct; 7(4):CD007362.Welliver, M, McDonough J, Kalynych N, et al. Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent. Drug Des Devel Ther. 2008; 2 : 49–59.Keating, GM Sugammadex: a review of neuromuscular blockade reversal. Drugs. 2016; 76 (10):1041–1052.

21 A 42‐year‐old man with no past medical history was in a motor vehicle crash and sustained a large subdural hematoma. The patient is intubated and taken to the operating room for a decompressive craniotomy. On postoperative day 6 while still intubated, the patient develops thick purulent‐looking secretions, has a WBC 13 000, and a fever to 38.4°C. Blood cultures, urine cultures, and bronchial alveolar lavage are obtained. What should be the empiric therapy for his suspected ventilator‐associated pneumonia?Vancomycin and ciprofloxacinVancomycin and gentamicinVancomycin and cefepimeCeftriaxone and azithromycinAmpicillin‐sulbactam and doxycyclinePer 2016 guidelines, antibiotic coverage for ventilator‐associated pneumonia (VAP) should include an active agent against MRSA when risk factors for antimicrobial resistance is present (prior IV antibiotics within 90 days, septic shock at time of VAP, ARDS preceding VAP, 5 or more days of hospitalization prior to VAP, acute renal replacement therapy). This patient most likely received antibiotics prior to his craniotomy and has been in the hospital > 5 days, and therefore needs both MRSA and gram‐negative coverage. This patient does not require double Pseudomonas coverage assuming he is in an intensive care unit that has antimicrobial resistance defined as < 10% of gram‐negative isolates resistant to an agent considered for monotherapy. Fluoroquinolones and aminoglycosides (Answers A & B) should not be used as monotherapy for gram‐negative coverage for ventilator‐associated pneumonia. Answers D and E are both reasonable treatments for community‐acquired pneumonia but are not appropriate for ventilator‐associated pneumonia. In this case, cefepime would be preferred to piperacillin‐tazobactam for gram‐negative coverage as cefepime has CNS penetration and this patient has had neurosurgical intervention.Answer: CKalil AC, Metersky ML, Klompas M,et al. Management of adults with hospital‐acquired and ventilator‐associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016; 63 (5): e61–e111.Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital‐acquired pneumonia and ventilator‐associated pneumonia: guidelines for the management of hospital‐acquired pneumonia (HAP)/ventilator‐associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J. 2017; 50 (3):1–26. PMID: 28890434.

22 A 33‐year‐old man, otherwise healthy, has acute appendicitis and will be undergoing a laparoscopic appendectomy. He mentions both his father and brother have been diagnosed with malignant hyperthermia. The patient has never had surgery before and has not been tested for the gene. Which is the best plan for anesthesia?Succinylcholine followed by isofluraneSuccinylcholine followed by desfluraneRocuronium followed by sevofluraneRocuronium followed by propofolRocuronium followed by nitrous oxideMalignant hyperthermia is a rare autosomal dominant disorder which is characterized by skeletal muscle hypermetabolism following exposure to halogenated anesthetics, succinylcholine, or rarely, physiologic stress. The mutation is often found on the RYR1 gene. Exposure to halogenated gasses or succinylcholine causes uncontrolled release of calcium from the sarcoplasmic reticulum leading to sustained muscle contraction. Signs and symptoms are tachycardia, tachypnea, hypoxemia, hypercarbia, metabolic acidosis, hyperkalemia, cardiac dysrhythmias, hypotension, skeletal muscle rigidity, and hyperthermia. Earliest signs are often hypercarbia and tachypnea followed by hyperthermia. Treatment is to stop the inciting agent, call for help, administer dantrolene 2.5 mg/kg until the reaction subsides, increase tidal volume, start aggressive cooling measures, treat arrythmias (avoid calcium channel blockers), check electrolytes, and continue dantrolene 1 mg/kg every 4 hours for 24 to 48 hours. The gold standard test is the caffeine halothane contracture test. As this requires a muscle biopsy, genetic testing is becoming more common.Succinylcholine and the halogenated gasses (isoflurane, desflurane, and sevoflurane) are known triggers for malignant hyperthermia, and should be avoided in this patient (Answers A, B, C). While nitrous oxide (Answer E) is not a halogenated gas, it is not typically used with laparoscopic surgeries as there is concern for bowel distension.Answer: DWatt S, McAllister RK . Malignant Hyperthermia. Stat Pearls Publishing . 2020Ruffert H, Bastian B, Bendixen D, et al. Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia group. Br J Anaesth. 2021; 126(1):120–130. doi: https://doi.org/10.1016/j.bja.2020.09.029. Epub 2020 Oct 31. PMID: 33131754