Board Review Session V Saturday, August 20, 2011 Questions With Answers and Rationales 64 A 55-year-old woman receiving warfarin for atrial fibrillation is transferred to your ICU with a left thalamic bleed At an outside hospital she was awake and aphasic, with a right facial droop and right-sided weakness She had onset of somnolence and irregular breathing and was placed on invasive mechanical ventilation On arrival to the ICU, her pulse rate is 60/min and BP is 200/90 mm Hg She does not follow commands and has no eye opening Pupils are mm on the left and mm on the right with extensor posturing in all extremities Which of the following is the most appropriate next step in her management? a Antiepileptics b Mannitol c Corticosteroids d Reversal of coagulopathy 65 A 26-year-old woman taking oral contraceptives presents to the emergency department with a 1-day history of headache, nausea, and vomiting Two hours ago she had a generalized seizure lasting minutes On examination she is awake and alert, with BP of 120/70 mm Hg, HR of 72/min, RR of 18/min, and temperature of 39.2°C (102.5°F) Her fundoscopic examination shows papilledema The rest of the neurological exam is unremarkable Meningitis is suspected and a lumbar puncture is planned As the physician prepares to leave the room, the patient has a seizure Five minutes after onset, which of the following would be the most effective initial therapy in her management? a Phenytoin b Diazepam c Lorazepam d Phenobarbital 66 A 55-year-old woman with hypertension is admitted to the ICU with slurred speech and unsteadiness, with a tendency to fall to the left On examination her BP is 150/90 mm Hg and pulse rate is 96/min She has dysarthria, limited abduction of the left eye, leftsided weakness, and ataxia on finger-nose testing and knee-heel testing on the left side Brain CT reveals a 3.4-cm left cerebellar bleed, with compression of the ambient cistern and brainstem and hydrocephalus Which of the following therapies would help the patient the most? a Corticosteroids b Controlling blood pressure c Posterior fossa decompression d Conservative management 67 A 65-year-old man presents with ascending paralysis of his lower extremities The paralysis increases subacutely over several days, accompanied by only minor sensory defects A diagnosis of Guillain-Barre syndrome is made The patient has significant exertional angina despite coronary artery stenting and aggressive medical care Which of the following would be the best choice for management of his Guillain-Barre syndrome? a Observation b Plasma exchange c IV immunoglobulin d Prednisone e Cyclophosphamide 68 A previously healthy, 67-year-old man presents with a 2-day history of increasing dyspnea, tingling in the extremities, and difficulty arising from a chair or turning in bed His examination shows profound weakness, absent reflexes, and normal sensory examination findings The most likely diagnosis is: a Botulism b Syringomyelia c Guillain-Barré syndrome d Cervical cord metastasis from lung cancer e Myasthenia gravis 69 Which of the following patients is most likely to benefit from therapeutic hypothermia (temperature 32°C–34°C [89.6°F–93.2°F])? a.20-year-old man with blunt head injury secondary to car crash, diffuse axonal injury on CT, and Glasgow Coma Scale score of on ICU admission b 65-year-old woman with acute left hemiplegia, altered mental status, and acute ischemia in the right middle cerebral artery territory on CT c 55-year-old man with anterior acute myocardial infarct who was admitted to the ICU after percutaneous coronary intervention, intubated and in cardiogenic shock d 43-year-old woman with out-of-hospital cardiac arrest who arrives to the hospital with restored spontaneous circulation and has Glasgow Coma Scale score of 15 e 58-year-old man admitted to the hospital with pneumonia who has an in-hospital cardiac arrest from ventricular tachycardia and is transferred to the ICU with return of spontaneous circulation, intubated and unconscious 70 A 53-year-old woman is evaluated in the emergency department after day of severe right flank pain, fever, and mild nausea Urinalysis shows many leukocytes and leukocyte casts Gram stain of her urine shows gram-positive cocci, and therapy with vancomycin and gentamicin is started Despite therapy, the patient develops progressive hypoxemia and requires mechanical ventilation On examination, she appears very anxious but is not trying to remove the endotracheal tube or any other support devices Her temperature is 37.5°C (99.5°F), pulse rate is 130/min, and blood pressure is 120/60 mm Hg Electrocardiography shows sinus tachycardia Blood and urine cultures grow Enterococcus faecalis While the patient is on mechanical ventilation, which of the following is the most appropriate sedation strategy? a Sedation with intermittent paralytics as tolerated b Deep continuous sedation c Intermittent bolus dosing with daily awakening d No sedation 71 A 28-year-old man is admitted to the ICU after sustaining a large aneurysmal subarachnoid bleed and is intubated for airway protection and ventilatory support Because of increased intracranial pressure and patient-ventilator dyssynchrony, propofol infusion is started at 100 μg/kg/min The patient’s medical course is complicated by gram-positive sepsis and adrenal insufficiency on day in the ICU, for which he is treated with appropriate broad-spectrum antibiotic therapy, volume resuscitation, norepinephrine, and hydrocortisone with the goal of maintaining a mean arterial pressure greater than 65 mm Hg On day 4, the patient remains sedated on mechanical ventilation and appears to be improving On day 5, he develops acute kidney injury, hyperkalemia, metabolic acidosis, rhabdomyolysis, and jugular venous distension with cardiac failure ECG shows no signs of an acute myocardial infarction or ischemia, and no peaked T waves or conduction disturbances Which of the following is the most urgent next step in the management of this patient? a Noncontrast CT of the head b Discontinuation of propofol c Plasmapheresis d IV heparinization 72 A 75-year-old man comes to the ICU after surgical repair of an infected aortic graft He is still intubated and requires mechanical ventilation for poor oxygenation and ventilation He is febrile, agitated, hypertensive, and tachycardic He has a history of coronary artery disease and had a stroke in the distant past The nurse asks about choice of sedation in this patient The goals are to minimize the potential for delirium and optimize the ability to follow the patient’s neurologic status and maintain his blood pressure Minimizing the cost of the patient’s hospitalization is also important Which of the following medications is most appropriate? A Lorazepam B Midazolam C Propofol D Dexmedetomidine E Remifentanil 73 A 75-year-old man who is intubated and mechanically ventilated is breathing at a rate of 40/min despite IV sedation The physician decides to use a neuromuscular blocker The nurse hands the physician a drug and the physician administers it intravenously When the physician asks for the name of the drug, the nurse is not sure whether it was succinylcholine or rocuronium The physician can most accurately determine which drug it is by: A Evaluating the tetanic fade with a neuromuscular monitor B Timing the initiation of paralysis after drug administration C Evaluating the response of the diaphragm to the drugs D Evaluating the response to reversal agents immediately after the administration of the neuromuscular blocker 74 Intubation is required for an 80-year-old woman who is hypotensive, tachycardic, and still hypoxic despite wearing a 100% rebreathing mask for sepsis and adult respiratory distress syndrome Which of the following estimates of the likelihood of complications including cardiac arrest during intubation is most likely to be correct? A 100% B 75% C 50% D 30% E 5% 75 An 82-year-old woman enters the ICU with fever and hypotension She has a history of intermittent bowel obstruction from adhesions secondary to a ruptured appendix more than 10 years ago Ceftazidime, vancomycin, and clindamycin are begun, and L of fluid administration results in a BP of 70/40 mm Hg An arterial and pulmonary artery catheter are inserted Baseline and post-therapy hemodynamics are as follows: HR, per BP, mm Hg (systolic/diastolic/mean) Right atrial pressure, mm Hg (mean) Right ventricular pressure, mm Hg (systolic/diastolic) Baseline 82 70/40/50 Following Therapy 90 105/60/70 25/3 26/3 Pulmonary artery pressure, mm Hg (systolic/diastolic) Pulmonary artery occlusion pressure, mm Hg (mean) Cardiac output, L/min Urine output, mL/h Splanchnic blood flow Blood lactate concentrations, mg/dL 27/18 26/18 16 3.5 decreased 6.8 16 4.8 30 increased 2.7 Which of the following medications was most likely administered? a Vasopressin, high dose (0.1–0.4 U/min) b Vasopressin, low dose (0.01–0.03 U/min) c Dopamine d Norepinephrine 76 A 66-year-old man enters the ICU with severe dyspnea due to acute heart failure He has a long-standing history of coronary artery disease with coronary artery bypass graft surgeries, the first 15 years ago, and again years ago An echocardiography performed months ago showed multiple wall motion abnormalities with a left ventricular ejection fraction of 25% His dyspnea continues despite high doses of IV furosemide, and a pulmonary artery catheter is placed with baseline and post-therapy values shown below: Hemodynamic profile Heart rate, beats/min Blood pressure, mm Hg (systolic/diastolic/mean) Right atrial pressure, mm Hg (mean) Right ventricular pressure, mm Hg (systolic/diastolic) Pulmonary artery pressure, mm Hg (systolic/diastolic/mean) Pulmonary artery occlusion pressure, mm Hg (mean) Cardiac output, L/min Urine output, mL/min Baseline 84 98/60/70 18 50/20 Following Therapy 86 95/60/68 40/10 50/28/30 40/18/20 28 2.8 10 16 2.9 40 Which of the following medications were administered to this patient?” a Nitroglycerin b Nitroprusside c Milrinone d Dobutamine Formatted: Italian (Italy) Formatted: Italian (Italy) Formatted: Italian (Italy) Formatted: English (U.S.) Formatted: English (U.S.) Formatted: English (U.S.) 77 A 69-year-old man with HIV infection was evaluated one year ago with a CD4 cell count of 30/µL and a viral load of 100,000 RNA copies per microliter He was treated with lopinavir/ritonavir and lamivudine/zidovudine, and month ago his CD4 cell count was 210/µL and his viral load was less than 50 RNA copies per microliter This morning, he had a seizure and was brought to the emergency department CT of his head shows a single 4-cm mass with surrounding edema in his right frontal lobe He is transferred comatose to the ICU His laboratory results are as follows: WBCs, 500/µL (90% neutrophils); bilirubin, 2.1 mg/dL; alkaline phosphatase, 310 U/L; aspartate aminotransferase and alanine aminotransferase, twice the normal range Which of the following is the most likely diagnosis of this lesion? a Toxoplasmosis b Lymphoma c Mycobacterium tuberculosis d Malignant glioblastoma e Cytomegalovirus 78 A patient with a stool toxin assay positive for Clostridium difficile colitis is treated with IV metronidazole The patient improves during 10 days of therapy, but week after completing therapy, the diarrhea recurs Which of the following is the most appropriate next step? a Treatment with oral vancomycin b Treatment with IV vancomycin c Treatment with oral Saccharomyces boulardii d Treatment with nitazoxanide e Antibiotic susceptibility testing of a stool isolate of Clostridium difficile Responses and Rationales: 64 Correct Answer: B Mannitol Rationale: The patient has warfarin-associated intracranial hemorrhage She is manifesting signs of herniation with left third nerve palsy and Cushing triad (bradycardia, irregular respiratory pattern, and systemic hypertension) from increased intracranial pressure (ICP) These findings should prompt the physician to immediately take steps to reduce the ICP Mannitol is an osmotic diuretic, used emergently to reduce ICP It reduces the rate of cerebrospinal fluid formation and blood viscosity by making red blood cells more flexible Other measures which can be used to reduce ICP are elevation of the head of the bed, hyperventilation, hypertonic saline (3%, 23.4%), and paralytics Emergent reversal of coagulopathy is indicated, but she needs immediate management of elevated ICP, so option D is incorrect Prophylactic antiepileptics have been shown to have worse outcomes following intracerebral hemorrhage, so option A is incorrect However, patients who develop clinical or electrographic seizures need to be treated with antiepileptics Corticosteroids are beneficial in vasogenic edema from intracranial tumors (primary and metastatic) Steroids have not been shown to be beneficial in intracerebral hemorrhage Thus option C is incorrect 65 Correct Answer: C Lorazepam Rationale: A double-blind study conducted by Veterans Affairs of 384 patients with generalized status epilepticus showed that initial treatment with lorazepam was more effective than phenytoin in controlling seizures It was not more efficacious than phenobarbital or diazepam, but was easier to use Another trial comparing lorazepam to diazepam showed that lorazepam was a better therapy than diazepam with regard to rate of termination of status epilepticus 66 Correct Answer: C Posterior fossa decompression Rationale: The patient is having signs of brainstem compression (left sixth nerve palsy) from a cerebellar bleed Patients with large cerebellar hemorrhages (>3 cm) who are deteriorating neurologically or having signs of brainstem compression or hydrocephalus should undergo surgical decompression (option C) Corticosteroids (option A) have not been shown to benefit patients with hematoma The patient’s blood pressure is fairly controlled, so option B is incorrect Conservative management would lead to worsening of brainstem compression and poor outcome, so option D is incorrect 67 Correct Answer: B Plasma exchange Rationale: Plasma exchange and IV immunoglobulin (Ig) are equivalently effective in randomized trials IV Ig is usually chosen for children because of venous access problems Patients with coronary artery or carotid artery disease tolerate plasma exchange better than the hyperviscosity of IV Ig Autonomic instability is not a contraindication to plasma exchange 68 Correct Answer: C Guillain-Barré syndrome Rationale: Guillain-Barré syndrome fits all of the points here Sensory complaints are common, but objective sensory findings very rare Botulism usually has prominent cranial nerve findings on presentation Syringomyelia would have sensory loss A cervical cord metastasis would produce a sensory level and hyperreflexia Myasthenia does not affect reflexes and lacks sensory concerns 69 Correct Answer: E 58-year-old man admitted to the hospital with pneumonia who has an in-hospital cardiac arrest from ventricular tachycardia and is transferred to the ICU with return of spontaneous circulation, intubated and unconscious Rationale: Based on results from clinical trials, the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association have recommended the use of therapeutic hypothermia after cardiac arrest Unconscious patients with return of spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32º-34°C (89.6°-93.2°F) for 12-24 hours (class IIa reccomendation) Similar therapy may be beneficial in patients with non-ventricular tachycardia arrest (out-of-hospital) or for in-hospital arrest (class IIb recomendation) Clinical trials in other areas such as traumatic brain injury, ischemic stroke, and myocardial infarct have been disappointing Current available literature does not support the routine use of therapeutic hypothermia in these clinical scenarios Based on these recommendations, patients in options D and E are the most likely to benefit The patient in option D is awake with a Glasgow Coma Scale score of 15 and therefore would not be considered a candidate for therapeutic hypothermia Hence, the patient in option E is the most likely to benefit from therapeutic hypothermia (intrahospital, ventriculartachycardia arrest, unconscious with return of spontaneous circulation) 70 Correct Answer: C Intermittent bolus dosing with daily awakening Rationale: A randomized, controlled trial by Girard et al in critically ill patients showed that intermittent bolus dosing of sedatives titrated against a validated sedation scale and with a daily spontaneous awakening trial with total cessation of sedatives yielded a 4-day reduction in ICU and hospital length-of-stay and an improvement in 1-year survival In critically ill patients, this method allows enough drug for comfort and reduces the likelihood of excess use of these potent psychoactive medications such as lorazepam A sedative drip with propofol would also be a consideration, as long as daily interruption of sedation was undertaken The newer-generation sedation scales are being widely adopted by ICUs to aid in drug titration and ease of communication The use of sedation with intermittent paralytics as tolerated has the potential for harming the patient via use of an agent (paralytics) that will increase risk of ICU-acquired weakness or paralysis without adequate sedation, and is generally reserved for patients demonstrating severe ventilator dyssynchrony (which is not mentioned as a current issue) Deep sedation until the patient is extubated would lead to unnecessarily prolonged and pronounced sedation The notion of trying to “eliminate” memories from the ICU appears to be a risk factor for posttraumatic stress disorder, which occurs in about 15% to 20% of ICU survivors Neuromuscular blockade with paralytic agents should be avoided unless absolutely necessary because of problems such as myopathy and prolonged paralysis 71 Correct Answer: B Discontinuation of propofol Rationale: This patient has the propofol infusion syndrome, and the drug should be discontinued and replaced by fentanyl and midazolam The propofol infusion syndrome is a rare and often fatal syndrome originally described in critically ill children undergoing long-term propofol infusion at high doses Recently, several cases have been reported in adults, mostly in patients with acute neurologic illnesses or acute inflammatory diseases complicated by severe infections or even sepsis, and receiving catecholamines and/or corticosteroids in addition to propofol The main features of the syndrome consist of cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure associated with hyperkalemia Central nervous system activation with production of catecholamines and corticosteroids, and systemic inflammation with cytokine production are priming factors for cardiac and peripheral muscle dysfunction High-dose propofol, but also supportive treatments with catecholamines and corticosteroids, act as triggering factors At the subcellular level, propofol impairs free fatty acid utilization and mitochondrial activity Imbalance between energy demand and utilization is a key pathogenetic mechanism, which may lead to cardiac and peripheral muscle necrosis The syndrome can be lethal if not identified early, and caution should be exercised when using prolonged (>48 hours) propofol sedation at doses higher than 75 μg/kg/min, particularly in patients with acute neurologic or inflammatory illnesses In these cases, alternative sedative agents should be considered immediately and monitoring of the plasma levels of troponin I, creatine kinase, and myoglobin should be undertaken There is no need to obtain a CT of the head, which would pose added risk of transport for the patient Beyond immediate discontinuation of the drug, the treatment of propofol infusion syndrome is supportive Supportive treatment may ultimately include bicarbonate infusion, hemodialysis, treatment of heart failure, and cardiac pacing for profound bradycardia There is no indication for IV heparin at this time Plasmapheresis has no role in managing the propofol infusion syndrome 72 Correct Answer: D Dexmedetomidine Rationale: An infusion of dexmedetomidine would meet most of the stated goals Data regarding dexmedetomidine as a sedative in critical care patients suggests it might decrease length of ICU stay Continuous sedation with dexmedetomidine results in significantly lower total ICU costs than midazolam infusions by decreasing length of ICU stay and duration of mechanical ventilation Dexmedetomidine appears to allow more normal cognition in patients, whereas infusions of propofol (option C) or benzodiazepines (options A and B) decrease cognition Infusions of dexmedetomidine have also been shown to be associated with decreased time in coma, allowing more neurologic status checks Dexmedetomidine does not affect respiratory rate but can cause bradycardia when given as a large bolus or in a large quantity during maintenance therapy Dexmedetomidine was shown to be particularly beneficial in improving brain dysfunction in patients with sepsis Lorazepam is an independent risk factor for the development of delirium in the ICU Thus, option A is incorrect When patients who were given midazolam were compared to those who had received dexmedetomidine, dexmedetomidine patients were extubated earlier by about days, with significantly less delirium and fewer infections Therefore, option B is incorrect Increased infections have been found in patients receiving remifentanil infusions (option E) There is no advantage to this type of sedation in terms of delirium, and it may be less advantageous given the issues of cost and possible immunomodulation 73 Correct Answer: A Evaluating the tetanic fade with a neuromuscular monitor Rationale: “A more accurate description of the effects of relaxants recognizes that the neuromuscular junction is a complex and dynamic system in which the phenomena produced by drugs are composites of actions that vary with drug, dose, activity in the junction and muscle, time after administration and presence of anesthetics or other drugs, and the age and condition of the patient.” It is now appreciated that there are nicotinic acetylcholine receptors [nAChRs] in the carotid body and on macrophages; thus, it is clear that the administration of these drugs can cause more effects than muscle paralysis Finally, neuromuscular function can also be affected by drugs that affect the conformational state of the nAChR, such as volatile anesthetics, cocaine, neostigmine, succinylcholine, calcium-channel blockers, phenothiazines, alcohol, and barbiturates These can cause desensitization of the receptors in that they bind to the receptors, but the sodium channel does not open and fewer receptor-channel units are available to carry transmembrane current Nicotinic autoreceptors are localized at the presynaptic nerve terminal and are responsible for the release of acetylcholine [ACh] into the synaptic cleft during highfrequency stimulation of the presynaptic nerve terminal These presynaptic cholinergic receptors are only inhibited by nondepolarizing neuromuscular blockers such as rocuronium and hexamethonium, and are nAChRs with alpha3-beta2 subunits Pharmacologic inhibition of these presynaptic alpha3-beta2 subunits during highfrequency, repetitive, tetanic stimulation causes a tetanic fade These receptors are not inhibited by succinylcholine, so a train-of-4 fade is not seen during the depolarizing block associated with the administration of succinylcholine Succinylcholine is like two molecules of ACh and it binds to the AChRs, opens the channel, passes current, and depolarizes the end plate; hence, it is a depolarizing neuromuscular blocker Increasing the dose of rocuronium from 0.6 mg/kg to 1.2 mg/kg shortens the onset time of complete neuromuscular blockade from 89 seconds to about 55 seconds This is a very similar amount of time for the initiation of complete blockade from an intubating dose of succinylcholine Thus, option B is incorrect Neuromuscular blockade, from both depolarizing and nondepolarizing neuromuscular blockers, develops more quickly in centrally located muscles, including the laryngeal muscles, the jaw muscles, and the diaphragm (option C), but the blockade also recovers more quickly Although it is true that reversal agents would typically have no effect after a depolarizing agent, whereas they should reverse a block from a nondepolarizing agent, timing is everything Reversal agents are usually administered when nondepolarizing neuromuscular agents have been given and there has been a recovery of the train of to a ratio of about 0.7 Reversal of neuromuscular blockade cannot be achieved immediately after the administration of neuromuscular blockers because the high doses of nondepolarizing neuromuscular blockers prevent the action of the reversal agent at the receptors Therefore, administration of a reversal agent immediately after the administration of the neuromuscular blocking drug would not help one discern whether a depolarizing or nondepolarizing agent was given, as it would have no effect Thus, option E is incorrect 74 Correct Answer: D 30% Rationale: This patient is at very high risk for complications during an emergent intubation She is elderly, she has severe underlying disease, she is unstable hemodynamically, and she is severely hypoxic despite receiving maximal supplemental oxygen Her chances of complications, according to the literature on this subject, are about 30%, and if she has complications, she has an increased chance of dying Longterm survival in patients who require emergent intubations is about 45-55% Furthermore, if the intubation is not achieved after one attempt, there is an increased rate of complications and mortality Therefore, to optimize the outcomes of emergent intubations in this high-risk population, paralytic agents should be utilized, skilled personnel (third-year anesthesia residents and/or anesthesia faculty) should be in attendance, and attempts at laryngoscopic intubation should be minimized prior to utilizing different devices or a surgical airway 75 Correct Answer: C Dopamine Rationale: This patient has septic shock from a probable abdominal source The therapeutic intervention produces an increase in heart rate, blood pressure, cardiac output, urine output, and splanchnic blood flow; a decrease in blood lactate; and no change in right atrial, right ventricular, pulmonary artery, and pulmonary artery occlusion pressures This pattern of hemodynamic effects is most consistent with dopamine administration, so choice C is correct Dopamine is a common choice for an initial vasopressor in circulatory shock A central and peripheral nervous system neurotransmitter and the biological precursor of norepinephrine, dopamine stimulates three different receptors: vascular dopaminergic, cardiac beta1-adrenergic, and vascular alpha-adrenergic At infusion rates of 1-3 µg/kg/min, dopaminergic effects usually dominate with vasodilation of renal, mesenteric, myocardial, and cerebral vascular beds At infusion rates of 5-10 µg/kg/min, cardiac output is preferentially augmented by increased cardiac contractility via cardiac beta1 stimulation At doses higher than 10 µg/kg/min, vascular alpha-adrenoreceptor effects become most pronounced, with increasing blood pressure If an adequate blood pressure is not achieved with up to 20 µg/kg/min of dopamine, norepinephrine should be initiated There is substantial interindividual response to dopamine, and all three effects — dopaminergic, cardiac beta1-adrenergic, and vascular alpha-adrenergic—commonly all exist at all dose levels of the drug Dopamine produces an increase in splanchnic flow and urine output via its dopaminergic effects, increase in cardiac output and heart rate via its cardiac beta1-adrenergic effects, and increase in blood pressure and decrease in lactate (due to increased tissue perfusion) via both its vascular alpha-adrenergic and its cardiac beta1-adrenergic effects Norepinephrine, another endogenous catecholamine, exerts powerful peripheral vasoconstrictive (via alpha-adrenergic receptors) and moderate inotropic cardiac effects (via cardiac beta1-adrenoreceptors) It causes an increase in blood pressure and (usually) a decrease in heart rate and cardiac output due to its predominant ability to increase afterload and blood pressure out of proportion to its ability to increase cardiac output via the cardiac beta-adrenoreceptors Norepinephrine administration in septic shock commonly results in increased urine output and decreased blood lactate due to improvement in blood pressure and tissue perfusion Norepinephrine does not cause an increase in splanchnic blood flow, so choice D is incorrect Vasopressin has vasoconstrictive and antidiuretic properties Vasopressin constricts vascular smooth muscle directly via V1 receptors In septic shock, vasopressin levels are reduced, and administration of exogenous vasopressin can produce a substantial vasopressor effect Prior to 10 years ago, vasopressin was used therapeutically at doses of 0.2 to 0.4 U/min to treat gastrointestinal hemorrhage from varices and other sources At this high dose, vasopressin produced profound systemic vasoconstriction with particularly profound constriction seen in the splanchnic, coronary, and peripheral vasculature This dose of vasopressin was frequently associated with mesenteric, coronary, and digital ischemia and infarction (choice A is incorrect) More recently, vasopressin has been used in a lower dose of 0.01 to 0.03 U/min, and at this dose it produces substantial generalized systemic vasoconstriction It results in increased blood pressure, and the increased afterload usually leads to decreased cardiac output and heart rate; thus, choice B is incorrect Because of an increase in blood pressure and tissue perfusion, urine output may increase and lactate may decrease Vasopressin does not increase splanchnic blood flow 76 Correct Answer: A Nitroglycerin Rationale: The hemodynamic effects involve little or no changes in heart rate, blood pressure, cardiac output, and urine output Substantial decreases are seen in right heart filling pressures with a decrease in right atrial, right ventricular, pulmonary artery, and pulmonary artery occlusion pressures This hemodynamic pattern is most typical of a predominantly venous vasodilator, and nitroglycerin is the agent most likely to produce such an effect Therefore, option A is correct Nitroglycerin has major vasodilating effects on the systemic venous circulation and the coronary circulation, acting directly on vascular smooth muscle cells to produce relaxation Although in high doses it may have some effect on the systemic circulation, its actions are predominantly on the venous circuit, producing a large decrease in preload and filling pressures Nitroglycerin has the ability to improve coronary blood flow and reduce ischemia in patients with coronary artery disease, even when coronary atherosclerosis is severe Because of its favorable effects on coronary ischemia, nitroglycerin is favored as a drug of first choice by cardiovascular physicians when dealing with severe coronary artery disease Dosages used intravenously usually range from to 200 µg/min A significant limitation of nitroglycerin therapy is the development of drug tolerance after about 24 hours of administration Nitroglycerin dosage will need to be increased to maintain the same therapeutic hemodynamic effect Therefore, nitroglycerin is only used for a short duration intravenously (24-48 hours), and when used chronically, a 6-hour nitrate-free period every 24 hours is necessary in order to prevent the development of nitrate tolerance Nitroprusside is a powerful venous and arterial vasodilator, and it produces a significant reduction of preload and afterload Nitroprusside infusions lead to decreases in right heart and pulmonary artery filling pressures, but they also result in decreased blood pressures and increased cardiac output in patients with a low cardiac output due to heart failure Thus, option B is incorrect Dosage range is usually 0.3 to 5.0 µg/kg/min Limitations of nitroprusside include potentially causing a “coronary steal” syndrome, in which blood flow may be directed away from ischemic myocardium Prolonged nitroprusside infusions in the setting of renal insufficiency may lead to accumulation of thiocyanate and cyanide toxicity This possible toxicity needs to be monitored when prolonged infusions are used Milrinone is a phosphodiesterase inhibitor that works downstream from the betaadrenergic receptor Milrinone has inotropic and vasodilator properties In addition to a decrease in filling pressures, it produces a significant increase in cardiac output (making option C incorrect) with minimal changes in heart rate and either no change or a small decrease in blood pressure In severe acute heart failure, milrinone is commonly used if dobutamine has failed to bring filling pressures and/or cardiac output into adequate range A major limitation of milrinone is its ability to cause hypotension, and with a relatively long elimination half-life of 2.3 hours, this hypotension can represent a prolonged problem Dobutamine is a potent beta1-adrenergic agonist with some beta2-adrenergic and alphaadrenergic agonist properties Its major effect is to increase myocardial contractility; it also causes an increase in cardiac output (making option D incorrect) and usually a mild increase in heart rate Because a decrease in systemic vascular resistance accompanies the increase in inotropy, dobutamine does not have a predictable effect on blood pressure: blood pressure may increase, decrease, or remain unchanged A major advantage of dobutamine is that its effective half-life is only a few minutes, so any drug-induced hypotensive episodes are brief A major limitation in heart failure is that beta-adrenergic receptors may be chronically down-regulated, limiting the hemodynamic effects of a beta1 agonist Also, many heart failure patients are now receiving long-term betablockade therapy, and this may reduce dobutamine’s effectiveness In such patients, milrinone may be a good alternative Dobutamine’s negatives also include a ventricular arrhythmia risk and tolerance to the drug, which has been demonstrated with infusions lasting >24 hours 77 Correct Answer: B Lymphoma Rationale: The differential diagnosis of a central nervous system mass lesion in a patient with HIV infection is primarily lymphoma versus toxoplasmosis Many other infections such as endemic fungi (Cryptococcus in particular) or Mycobacterium tuberculosis could cause this lesion, but they are less common The current CD4 cell count is an excellent indicator of susceptibility to infection A recent CD4 cell count of 210/µL makes toxoplasmosis unlikely This patient could have a glioblastoma, but lymphoma is more likely A polymerase chain reaction test of cerebrospinal fluid for Epstein-Barr virus would strongly support this diagnosis 78 Correct Answer: A Treatment with oral vancomycin Rationale: Therapy for Clostridium difficile colitis fails in 5-25% of cases Some patients fail to improve and some relapse Relapses are due either to failure to eradicate spores from the stool or to reacquisition of C difficile from the environment Retreatment could be approached with oral metronidazole, oral vancomycin, or a combination of both Nitazoxanide is active against C difficile, but its role in initial therapy or retreatment has not been clearly defined, so it is not the best option More than 95% of oral metronidazole is absorbed in the proximal small bowel, so there is no real pharmacologic difference between oral and IV routes of administration: both depend on bloodstream delivery to inflamed gastrointestinal mucosa Vancomycin is effective orally, but IV therapy does not attain high gastrointestinal levels and is not recommended The literature is filled with accounts of treatment failures If vancomycin must be given, and oral therapy is not feasible, a retention enema is more likely to be effective, but mechanical complications are a major concern with inflamed colonic mucosa Such enemas are rarely used in ICUs Gut recolonization with Saccharomyces has been shown to reduce the incidence of relapses, but recolonization should not be done without a course of oral or IV therapy The controlled study that showed efficacy in preventing relapses compared standard oral or IV antibiotic therapy plus Saccharomyces to antibiotic therapy alone Testing stool for fecal leukocytes provides data but is not a sensitive test Testing of stool by the lactoferrin test is more sensitive but not specific Testing stool for toxin after an initial positive result is not helpful Even in successfully treated patients, toxin may persist for many days or weeks and its presence does not distinguish why patients are failing Almost no laboratories routinely perform C difficile susceptibility testing Metronidazole resistance does occur in about 7% of cases, but the clinical significance of this resistance is uncertain given the high levels of drug that are attained in stool, particularly when the colon is inflamed Thus, the almost universal approach is to retreat the patient with oral or IV metronidazole or oral vancomycin