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Sedation, Pain Management, and Pharmacology 

Sedation, Pain Management, and Pharmacology
Chapter:
Sedation, Pain Management, and Pharmacology
Source:
Anesthesiology Critical Care Board Review
Author(s):

Sophie Samuel

and Jennifer Cortes

DOI:
10.1093/med/9780190908041.003.0007

Questions

1. A 59-year-old female with no significant past medical history who presents to the emergency department (ED) with severe shortness of breath, tachypnea, and altered mental status is intubated for hypoxic respiratory failure. Chest radiograph is shown below. Vital signs while on fentanyl 100 mcg/hr, norepinephrine 0.75 mcg/kg per minute, and vasopressin 0.03 units/minute are as follows:

  • Heart rate (HR): 124 bpm

  • Blood pressure (BP): 129/84 mm Hg

  • Respiratory rate (RR): 26 breaths/minute (on mechanical ventilation)

  • Temperature: 102.1° F

The patient is admitted to the intensive care unit (ICU) with metabolic acidosis. During initial assessment of the patient, she is found to have a Behavioral Pain Score (BPS) score of 3 and a Richmond Agitation and Sedation Scale (RASS) score of +2. Which one of the following is the BEST sedative to initiate on admission?

Sedation, Pain Management, and Pharmacology

  1. A. Propofol

  2. B. Dexmedetomidine

  3. C. Hydromorphone

  4. D. Midazolam

2. On day 2 of hospitalization, the the same patient as in question 1 remains in septic shock and is now experiencing multiple-organ failure, including acute kidney injury and acute liver failure, and severe acute respiratory distress syndrome (ARDS), with a PaO2/FiO2 ratio of 99. The patient is made prone and needs to be paralyzed. What is the MOST appropriate paralytic to initiate?

  1. A. Succinylcholine

  2. B. Rocuronium

  3. C. Vecuronium

  4. D. Cisatracurium

3. On ICU day 13, in the same patient as in questions 1 and 2, the ARDS, septic shock, and multiple-organ failure have resolved. She cannot be extubated due to agitation. During rounds, she has a RASS score of +2 and BPS score of 4, and she nearly self-extubates despite orientation and encouragement from staff and family. The Confusion Assessment Method for the ICU (CAM-ICU) is positive, and she is deemed to have hyperactive delirium. Which of the following is the BEST intervention?

  1. A. Quetiapine

  2. B. Rivastigmine

  3. C. Midazolam

  4. D. Haloperidol

4. A 26-year-old male is transferred to the ICU from an outside hospital after ingestion of 30 sertraline 50-mg tablets approximately 6 hours ago. He is experiencing altered mental status with a Glasgow Coma Scale (GCS) score of 10, diaphoresis, and muscle rigidity. His vital signs are as follows:

  • HR: 92 beats/minute

  • BP: 168/89 mm Hg

  • RR: 18 breaths/minute

  • Temperature: 101.4° F

Which of the following are the MOST appropriate intervention?

  1. A. Activated charcoal

  2. B. Ampoule of sodium bicarbonate

  3. C. Cyproheptadine

  4. D. Lorazepam

5. A 19-year-old female is “found down” in her dorm room by her roommate with an empty bottle of amitriptyline next to her. She was transported to the ED by emergency medical services (EMS) and intubated en route. The roommate reports that she last saw the patient normal the previous night and doesn’t know how many pills were in the bottle. On physical examination, she has a GSC score of 5 with dry mucous membranes. Her vital signs are as follows:

  • HR: 114 bpm

  • BP: 111/68 mm Hg

  • RR: 16 breaths/minute (on mechanical ventilation)

  • Temperature: 100.8° F

ECG reveals sinus tachycardia with a QRS of 129 milliseconds. Which of the following is the MOST appropriate initial therapy?

  1. A. 0.9% sodium chloride bolus

  2. B. Sodium bicarbonate

  3. C. Magnesium sulfate

  4. D. Propafenone

6. A patient is transferred to the ICU from the ED with a diagnosis of bipolar disorder. He has been managed by his psychiatrist for 15 years, and his medication reconciliation form demonstrates compliance with his medications up to this point. Which of the following is the MOST likely lab finding?

  1. A. Leukocytopenia

  2. B. Hypernatremia

  3. C. Thrombocytosis

  4. D. Hypokalemia

7. A 44-year-old male with a past medical history of glucose-6-phosphate dehydrogenase (G6PD) deficiency presents to the ED with complaints of shortness of breath, hemoptysis, night sweats, and weight loss. He was released from prison 6 months ago and has a pattern of known drug abuse. On physical examination, he is found to have oral thrush and complains of difficulty swallowing that limits his ability to eat.

Which of the following is the MOST appropriate therapy for the treatment his dysphagia?

  1. A. Nystatin

  2. B. Micafungin

  3. C. Fluconazole

  4. D. Amphotericin B

8. In the same patient as question 7), the chest radiograph reveals a cavitary lesion, and sputum is sent for acid-fast bacilli smear microscopy along with a nucleic acid amplification test (NAAT-TB). In 48 hours, the microbiology lab calls with results of a positive NAAT. Which of the following medications is NOT part of the initial treatment of pulmonary Mycobacterium tuberculosis?

  1. A. Ethambutol

  2. B. Isoniazid

  3. C. Clarithromycin

  4. D. Pyrazinamide

9. The same patient as questions 7 and 8, is found to be HIV positive with a viral load of 88,000 copies/mL and an absolute CD4 count of 164. Which of the following medications is MOST appropriate for primary prevention of opportunistic infections?

  1. A. Sulfamethoxazole-trimethoprim

  2. B. Azithromycin

  3. C. Dapsone

  4. D. Atovaquone

Questions 10 to 12 pertain to the following case:

A 53-year-old woman with a history of hypertension and hyperlipidemia presents with sudden-onset headache and stupor. In the ED, she is minimally responsive to pain and has a flaccid left arm and increased tone in her lower extremities; she then requires intubation. Noncontrast head computed tomography (CT) is completed on admission and shown here.

Sedation, Pain Management, and Pharmacology

10. The patient is transferred to the ICU for further management and placement of an external ventricular drain (EVD). Which prophylactic antibiotic should be used before placing an EVD?

  1. A. Cefazolin

  2. B. Cefepime

  3. C. Ciprofloxacin

  4. D. Piperacillin-tazobactam

11. The same patient has now been hospitalized in the ICU for 3 days. Her EVD is still present, and in the intervening time she has required endotracheal intubation and mechanical ventilation because of a poor neurological exam. The chest radiograph is shown here. She has temperature of 38.4° C, white blood cell (WBC) count of 19 × 103 cells/mm3, and purulent sputum. You decide to perform bronchoalveolar lavage (BAL) of the lung to assess for ventilator-associated pneumonia (VAP).

Sedation, Pain Management, and Pharmacology

Which is the MOST likely causative pathogen of this patient’s VAP?

  1. A. Methicillin-resistant Staphylococcus aureus (MRSA)

  2. B.Pseudomonas aeruginosa

  3. C.Streptococcus pneumoniae

  4. D.Legionella pneumophila

12. Which empiric antibiotic regimen is BEST for the likely causative pathogen of the patient’s suspected VAP?

  1. A. Ceftriaxone

  2. B. Vancomycin

  3. C. Piperacillin-tazobactam

  4. D. Cefepime

Questions 13 and 14 pertain to the following case:

A 37-year-old man has a past medical history significant for quadriplegia since the age of 28 following injuries sustained in a motor vehicle collision. He has no known drug allergies. He reports foul odor from a sacral wound on dressing changes and overall feeling unwell. Vitals on admission include the following:

  • HR: 112 bpm

  • BP: 98/64 mm Hg

  • RR: 18 breaths/minute

  • Temperature: 38.7° C

Physical examination reveals a large foul-smelling sacral decubitus ulcer, and laboratory evaluation reveals WBC 18.7 × 103 cells/mm3. Chart review discloses a history of extended-spectrum beta-lactamase (ESBL)-producing Enterobacter aerogenes and MRSA from the wound.

13. Which one of the following combination regimens is BEST to administer at this time?

  1. A. Ceftriaxone and daptomycin

  2. B. Cefepime

  3. C. Piperacillin-tazobactam and vancomycin

  4. D. Meropenem and daptomycin

14. The patient is taken to the surgery for operative debridement. Culture results on postoperative day 3 are reported here:

Acinetobacter baumannii

Antibiotic

Minimum Inhibitory Concentration

Interpretation

Ampicillin-sulbactam

>32/16

R

Ceftriaxone

>64

R

Cefepime

>32

R

Gentamicin

>16

R

Levofloxacin

>8

R

Meropenem

4

I

Piperacillin-tazobactam

>128/4

R

Tobramycin

>16

R

Which one of the following is the BEST antibiotic strategy until additional susceptibility results are available?

  1. A. Continue with meropenem

  2. B. Change to amikacin

  3. C. Add colistin to meropenem

  4. D. Result is likely contamination

15. A 65-year-old woman admitted to the surgical ICU after being taken to an operating room emergently for partial bowel resection with primary anastomosis for mid to small bowel necrosis and perforation secondary to severe peripheral vascular disease. The surgical team reported significant peritoneal contamination with evidence of peritonitis. The patient received perioperative cefazolin and metronidazole. Which empiric antibiotic regimen would be MOST appropriate?

  1. A. Piperacillin-tazobactam

  2. B. Cefazolin

  3. C. Ertapenem

  4. D. Metronidazole

Question 16 and 17 pertain to the following case:

A 27-year-old 77-kg, 67-inch male presents to your hospital ED with headache, altered mental status, lethargy, and a temperature of 39° C. CT and magnetic resonance imaging (MRI) suggest encephalitis. Lumbar puncture (LP) is performed, and routine diagnostic lab tests are ordered on his cerebral spinal fluid (CSF). Complete blood count, basic metabolic panel, and blood cultures are pending.

16. What is the BEST regimen to initiate as empiric therapy?

  1. A. Ceftriaxone and linezolid

  2. B. Ceftriaxone, linezolid, and acyclovir

  3. C. Ceftriaxone, vancomycin, and acyclovir

  4. D. Cefepime, vancomycin, and acyclovir

17. The patient’s CSF panel is as follows:

  • Opening pressure: 43 mm Hg

  • WBC count: 3500 cells/mm3 (24% neutrophils)

  • Protein: 178 mg/dL

  • Glucose: 62 mg/dL (serum glucose 100 mg/dL)

  • Red blood cell (RBC) count: 1000 cells/mm3

Bacterial antigen and CSF Gram stain were negative. Results of the remaining lab tests came back normal except for elevated serum WBC count of 14 × 103 cells/mm3. A CSF herpes simplex virus (HSV) polymerase chain reaction (PCR) test is positive, and blood cultures are negative. Which of the following is the BEST treatment regimen?

  1. A. Oral (PO) acyclovir for 14 days

  2. B. Intravenous (IV) acyclovir for 7 days

  3. C. IV acyclovir for 14 days

  4. D. Continue antibiotics with acyclovir

18. Following a business trip to Idaho, a middle-aged man with past medical history of obesity, type 2 diabetes (controlled with diet), and reflux disease presents with hyperglycemia, fever, confusion, abdominal pain, and rash. He takes pantoprazole daily; otherwise, his family denies any other chronic pharmacotherapy. On physical examination, a papule (shown here; image courtesy of Richard Jahan-Tigh, MD, MS) is noted on his right thigh.

Sedation, Pain Management, and Pharmacology

Which of the following is the MOST appropriate treatment?

  1. A. Linezolid

  2. B. Doxycycline

  3. C. Amoxicillin

  4. D. Discontinue pantoprazole

19. A 28-year-old female G1P1001 is involved as a passenger in a motor vehicle collision with rollover. She is found to have a fractured humerus and left lung contusion and is admitted to the ICU for management. Abdominal CT shows no acute abnormalities, and FAST examination is negative. The bedside nurse reports that she complains of pruritis ani, abdominal pain, and nausea and had been intending to see her primary physician for her abdominal symptoms. Which of the following would be the MOST appropriate initial treatment?

  1. A. Mebendazole

  2. B. Ciprofloxacin

  3. C. Cefazolin

  4. D. Vancomycin

Answers

1. Answer: D

Although the 2013 Pain, Sedation, Delirium guidelines recommend non–benzodiazepine-based sedation as the preferred type of sedation, this patient should not receive propofol or dexmedetomidine because she is in septic shock and both medications have a high incidence of hypotension and can increase vasopressor requirements. Hydromorphone is not appropriate because the patient is already receiving analgosedation, and her current BPS score is 3, which is indicative of no pain. Additionally, while hydromorphone may be used as a sedative agent, it is not a hypnotic agent, which may prevent a patient with pulmonary disease from tolerating mechanical ventilation. Additionally, because the duration of action of hydromorphone is 3 to 4 hours, the pharmacokinetics of such a drug lend it to accumulation. The BPS was first described in 2001 and includes a summative score of the following factors, with a total score range of 3 to 12:

Item

Description

Score

Facial expression

Relaxed

1

Partially tightened (e.g., brow lowering)

2

Fully tightened (e.g., eyelid closing)

3

Grimacing

4

Upper limbs

No movement

1

Partially bent

2

Fully bent with finger flexion

3

Permanently retracted

4

Compliance with ventilation

Tolerating movement

1

Coughing but tolerating ventilation for most of the time

2

Fighting ventilator

3

Unable to control ventilation

4

Midazolam is a benzodiazepine, and benzodiazepine-based sedation, compared with non–benzodiazepine-based sedation, is associated with a shorter ICU length of stay and duration of mechanical ventilation. However, a landmark trial by Riker et al. failed to demonstrate a statistically significant increase in ICU length of stay when midazolam sedation was compared with dexmedetomidine sedation, but there was decrease in time to extubation. Midazolam remains an option for the acute treatment of agitation in mechanically ventilated patients given its clinical efficacy and hemodynamic profile. If a benzodiazepine is required, the smallest possible dose should be administered that will achieve the intended clinical outcome.

Midazolam has a benzepine ring that is commonly suspended in the preservative benzyl alcohol. In an acidic environment, the benzepine ring opens, facilitating solvency in water. As soon as parenteral midazolam encounters a neutral pH, the benzepine ring closes, and midazolam becomes lipid soluble. Parenteral midazolam is prepared with hydrochloric acid to achieve appropriate solubility. Benzyl alcohol toxicity has been associated with anion gap metabolic acidosis, but this is not frequently seen in adults receiving midazolam. The benzodiazepines diazepam and lorazepam, when administered as an IV infusion, may lead to an anion gap metabolic acidosis because they have significant quantities (50–80% volume) of propylene glycol as a diluent; propylene glycol toxicity is commonly manifested by seizures, renal failure, and central nervous system depression.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Sedative-hypnotics

References

Barr J, Fraser GL, Puntillo K et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263–306.Find this resource:

Fraser GL, Devlin JW, Worby CP et al. Benzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Crit Care Med 2013;41:S30–S38.Find this resource:

Payen JF, Bru O, Bosson JL et al. Assessing pain in critically ill sedated patients by using a behavioral pain scale. Crit Care Med 2001;29(12):2258–2263.Find this resource:

Riker RR, Shehabi Y, Bokesch PM et al.; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009;301(5):489–499.Find this resource:

Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med 2009;10(2):256–259.Find this resource:

2. Answer: D

Succinylcholine is a depolarizing paralytic that is used in single doses as part of rapid-sequence intubation or as intermittent administration. Additionally, succinylcholine may cause vagal stimulation and therefore lead to bradycardia, though infrequently. Rocuronium (aminosteroid), vecuronium (aminosteroid), and cisatracurium (benzylisoquinoline) are non-depolarizing paralytics that can be administered as continuous infusions. Vecuronium and rocuronium undergo renal or hepatic elimination and therefore are affected by acute renal and hepatic failure. Because this patient is in multiple-organ failure, cisatracurium would be the most appropriate paralytic agent because elimination is dependent on Hoffman elimination.

Chiari I malformation (CIM) is a source of significant morbidity in the ICU population, and while neuromuscular blockade administration (aminosteroid or benzylisoquinoline type) is a risk factor, there are no studies evaluating a difference in bolus versus infusion therapy for developing CIM. Other risk factors for developing CIM include hyperglycemia, corticosteroids, catecholamines, aminoglycoside antibiotics, parenteral nutrition, vasopressors, and advanced age.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Neuromuscular blocking drugs

References

Lacomis D, Petrella JT, Giuliani MJ. Causes of neuromuscular weakness in the intensive care unit: a study of ninety-two patients. Muscle Nerve 1998;21(5):610–617.Find this resource:

Murray M, DeBlock H, Erstad B et al. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 2016;44:2079–2103.Find this resource:

Papazian L, Forel JM, Gacouin A et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107–1116.Find this resource:

3. Answer: A

There is no definitive pharmacologic therapy for the treatment of ICU delirium, although it occurs in up to 30% of hospitalized patients and is associated with increased morbidity and mortality. Atypical antipsychotics have been evaluated in a few studies, but only one study comparing quetiapine to placebo showed a difference in the duration of delirium. The Society of Critical Care Medicine guidelines suggest that atypical antipsychotics may reduce the duration of delirium, but this is a recommendation with low or very low evidence. Despite weak evidence, atypical antipsychotics may be administered to patients with hyperactive delirium but should be avoided in patients with risk for significant adverse events (e.g., torsades de pointes).

Impaired cholinergic neurotransmission has been demonstrated to have an important role in the development of delirium, and serum anticholinergic activity has been found to be elevated in patients with delirium. Additionally, drugs with anticholinergic effects (e.g., glycopyrrolate) have been known to cause delirium, especially in elderly patients. Nonetheless, rivastigmine is not an appropriate therapy for the treatment of delirium because it has been demonstrated to trend toward a longer duration of delirium; in fact, the trial evaluating this application of rivastigmine was terminated early because of an association with higher mortality. Benzodiazepines should be avoided unless patients are experiencing alcohol or benzodiazepine withdrawal due to increased duration of mechanical ventilation and are associated with precipitating more delirium.

While there is no published evidence showing a benefit of haloperidol for the treatment of delirium above other pharmacologic agents, it is the most frequently prescribed neuroleptic agent in the ICU. Haloperidol must be used with caution because it has a variety of adverse effects, including dystonias, neuroleptic malignant syndrome, extrapyramidal effects, and the most worrisome—torsades de pointes. It should not be given to patients with electrocardiographic evidence of prolonged QT interval. QT interval daily measurements are recommended when haloperidol is initiated.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antipsychotics

References

Barr J, Fraser GL, Puntillo K et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:263–306.Find this resource:

Devlin JW, Roberts RJ, Fong JJ et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010;38:419–427.Find this resource:

van Ejik MM, Roes KC, Honing ML et al. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicenter, double-blind, placebo-controlled randomized trial. Lancet 2010;376:1829–1837.Find this resource:

4. Answer: D

Serotonin syndrome, seizures, and cardiac conduction abnormalities are serious adverse effects of selective serotonin reuptake inhibitor (SSRI) overdose; while rare, these clinical findings are more associate with venlafaxine or citalopram. More severe complications following SSRI overdose may include a constellation of symptoms and signs referred to as serotonin syndrome; this may follow SSRI or selective serotonin-norepinephrine reuptake inhibitor (SNRI) overdose. This disorder results from excessive stimulation of central and peripheral serotonin receptors and is depicted by a triad of altered mentation, autonomic dysfunction, and neuromuscular hyperactivity. Signs and symptoms range from mild to very severe and include delirium, diaphoresis, diarrhea, hyperthermia, tremor, hyperreflexia, muscular rigidity, and clonus. Laboratory findings are generally nonspecific, including findings such as elevated white blood cell count, creatine phosphokinase, and hepatic transaminases. Serotonin syndrome tends to develop within 6 hours of the poisoning event.

Therapy for SSRI (and incidentally SNRI) overdose is primarily supportive, with the first and most accessible therapy being the discontinuation of the offending drugs. Benzodiazepines are administered as first-line agents for agitation and muscle rigidity. Activated charcoal is effective only when administered within 1 hour of ingestion and is excluded as an option here given the timing of the patient’s admission. Since the patient presented 6 hours after ingestion, he may actually be harmed because he is experiencing altered mental status and at increased risk for aspiration. Sodium bicarbonate should not be administered at this time because the patient is not experiencing QRS or QT prolongation. However, in the setting of tricyclic antidepressant (TCA) overdose, sodium bicarbonate may be useful in treating QRS or QT prolongation.

Cyproheptadine is administered as an adjunct to benzodiazepines for agitation and muscle rigidity, but a loading dose of 12 mg should be administered. Use of cyproheptadine, a serotonin receptor antagonist, is normally reserved for serotonin syndrome or severe cases of overdose. Given the rarity of its necessity for administration, there are limited data on the use of cyproheptadine.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antidepressants; SSRIs

References

Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112–1120.Find this resource:

Reilly TH, Kirk MA. Atypical antipsychotics and newer antidepressants. Emerg Med Clin North Am 2007;25:477–497.Find this resource:

Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf 2008;7:587–596.Find this resource:

5. Answer: B

Impaired cardiac conduction as a result of sodium channel blockade is a manifestation of TCA overdose. Sodium bicarbonate should be administered in patients with a QRS great than 100 or impaired cardiac conduction who present following TCA overdose. The sodium load can overcome the TCA blockade of the sodium channels by increasing the electrochemical gradient. In addition, alkalization of the blood may increase protein binding of the TCA, therefore decreasing the amount of free drug. Additionally, by causing drug ionization, the alkalization process may serve to reduce the affinity of TCAs for the myocardial sodium channel receptor. Finally, by increasing the serum sodium concentration, sodium channel blockade may be overcome.

The patient is currently not hypotensive or in shock; therefore, a bolus of IV fluids is not indicated at this time. Furthermore, sodium chloride will not serve to alkalinize the blood given its pH of 5.5 and would therefore inhibit the process described previously.

Propafenone is a class 1C antiarrhythmic drug and primarily serves to block open sodium channels and slow conduction; it has a role, as dose flecainide, in treating widened QRS complex tachyarrhythmias because it slowly dissociates from the sodium receptor during diastole, thereby making it more effective at higher rates of tachycardia. In this case, because the patient experiencing TCA overdose, it would not be an appropriate therapy.

Hyperthermia is a manifestation of the anticholinergic effects of TCAs; therefore, magnesium is not the appropriate initial therapy. While it cannot be used to treat pyrexia, magnesium sulfate is commonly used to facilitate hypothermia. The proposed mechanism for supporting hypothermia is inhibition of shivering and increased vasodilation; additionally, improved post-hypothermia neurological outcomes after magnesium administration have been observed in clinical trials.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antidepressants; Tricyclic antidepressants

References

Alapat PM, Zimmerman JL. Chest 2008;133:1006–1013.Find this resource:

Blackman K, Brown SG, Wilkes GJ. Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. Emerg Med 2001;13:204–210.Find this resource:

Pimentel L, Trommer L. Cyclic antidepressant overdoses. Emerg Clin North Am 2007;25:477–497.Find this resource:

Zweifler RM, Voorhees ME, Mahmood MA, Parnell M. Magnesium sulfate increases the rate of hypothermia via surface cooling and improves comfort. Stroke 2004;35(10):2331–2334.Find this resource:

6. Answer: B

As a second-line agent, lithium use can result in many adverse effects, with the most common including nausea, tremor, thirst, polyuria, weight gain, loose stools, and cognitive impairment. Acute worsening of these symptoms may indicate lithium toxicity. Over the long term, lithium can adversely affect the kidneys and thyroid gland. Chronic lithium ingestion can cause resistance to antidiuretic hormone (ADH) by accumulating in the principal cells of the collecting duct. The accumulation interferes with the ability of ADH to increase water permeability, leading to nephrogenic diabetes insipidus. A potential mechanism for this is that lithium may increase expression of cyclo-oxyenase-2 and increase urinary prostaglandin excretion. Prostaglandin E2 induces lysosomal degradation of aquaporin-2 water channels and decreases the ability to concentrate the urine. In addition, cardiac rhythm disturbances have been described; these almost always occur in patients with preexisting cardiac disease. By extension, hypernatremia would be the expected laboratory abnormality in this presentation.

Lithium is known to been associated with leukocytosis with a reversible 2 × 109/L increase in WBC count at the initiation of therapy. In this case, diabetes insipidus is more likely given the chronic nature of this patient’s presentation. While lithium does not cause changes in platelet count, escitalopram (and SSRIs in general) has been shown to mildly decrease platelet count. Depression and antidepressants are thought to affect platelets because neurons and platelets share similar serotonin profiles, and changes in 5-HT2A receptor and the 5-HT transporter (5-HTT) of platelets can act as a surrogate biomarker to indicate depression. SSRIs have inhibitory effects on 5-HTT and serotonin receptors of platelets, thereby diminishing platelet aggregation. Because this patient has bipolar disorder, there is not an indication for SSRIs, making this answer a distractor.

Although checking serum chemistries is common when lithium therapy is initiated, it is not indicated after the patient is stabilized or after the first year of therapy. These labs are primarily used to assess creatinine and blood urea nitrogen. There are not expected potassium changes with lithium therapy.

Keywords: Specialized areas, Pharmacology (indications, contraindications, and complications); Antidepressants; Lithium

References

Behl Tapan, Kotwani A, Kaur, I, Goel H. Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus. Eur J Pharmacol 2015;755:27–33.Find this resource:

Lithium: a review of pharmacology, clinical uses, and toxicity. Eur J Pharmacol 2014;740:464–473.Find this resource:

Song HR, Jung YE, Wang HR et al. Platelet count alterations associated with escitalopram, venlafaxine and bupropion in depressive patients. Psychiatry Clin Neurosci 2012;66(5):457–459.Find this resource:

7. Answer: C

Oropharyngeal candidiasis with dysphagia is an indicator of esophageal candidiasis. Esophageal candidiasis should be treated with systemic therapy; therefore, nystatin is not an appropriate treatment option. Of note, because nystatin contains sucrose, its prolonged use can lead to dental caries. The treatment of choice for esophageal candidiasis is fluconazole. Fluconazole has an 80 to 90% effectiveness rate and was demonstrated to be superior to other azole derivatives by three randomized control trials. Echinocandins (caspofungin, micafungin, and anidulafungin) are associated with higher esophageal disease relapse rates compared with fluconazole. As a class of antifungals, echinocandins are notable in that they were the first antifungals to target the cell wall. Amphotericin is an effective treatment for esophageal candidiasis but should be used as an alternative agent secondary to its potential for nephrotoxicity.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antifungal

Reference

Pappas PG, Kaufman CA, Andes DR et al. Clinical practice guidelines for the management of candidiasis. Clin Infect Dis 2016;62:e1–e50.Find this resource:

8. Answer: C

The preferred regimen for tuberculosis that is not known to be drug resistant is 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4 months of isoniazid and rifampin. Clarithromycin is included in the treatment regimen for Mycobacterium avium complex but not M. tuberculosis.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antibiotics; tuberculosis

References

Nahid P, Dorman, SE, Alipanah N et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. CID 2016;63:e147–e195.Find this resource:

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed December 10, 2017.

9. Answer: D

Atovaquone is the appropriate prophylactic agent to start because this patient is at increased risk for developing Pneumocystis pneumonia with a CD4 count of less than 200. Azithromycin is initiated for prophylaxis against M. avium complex when the absolute CD4 count is less than 50. Drugs such as dapsone and sulfamethoxazole increase the likelihood of cell hemolysis in patients with G6PD deficiency. Recall that G6PD is an important enzyme for maintaining red cell wall structural integrity. This is related to the fact that blood cells contain relatively high concentrations of reduced glutathione; glutathione functions as an intracellular reducing agent, thereby protecting the cell against oxidant injury. In patients with G6PD deficiency, acute hemolysis can occur with oxidant injury from medications, acute illnesses, and certain foods. Drugs that lead to hemolysis in this condition interact with hemoglobin and oxygen, leading to the formation of H2O2, among other oxidizing radicals, within RBCs. When these oxidants accumulate inside of these RBCs, hemoglobin and other proteins are oxidized because there is insufficient glutathione, leading to cell lysis. A comprehensive list of common medications that may lead to hemolysis in G6PD deficiency is lengthy and can be found at https://www.g6pd.org/en/G6PDDeficiency/SafeUnsafe/DaEvitare_ISS-it.

Antibiotics that are contraindicated in G6PD deficiency include dapsone, nitrofurantoin (and related drugs), and primaquine. Common antibiotics that have been considered unsafe by at least one source but could be safe at therapeutic doses based on an updated review of the literature include the following:

Antimalarials

Chloroquine, mepacrine, quinine

Fluoroquinolones

Ciprofloxacin, levofloxacin, ofloxacin

Sulfonamides

Co-trimoxazole, trimethoprim-sulfamethoxazole

Antimicrobials

Chloramphenicol, furazolidone, isoniazid, mepacrine

Therefore, administration of dapsone and sulfamethoxazole should be avoided in this patient because of his history of G6PD deficiency.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antibiotics; Other

References

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed on December 10, 2017.

Youngster I, Arcavi L, Schechmaster R et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence based review. Drug Saf 2010;33:713–726.Find this resource:

10. Answer: A

This patient is presenting with subarachnoid hemorrhage, as evidenced by the CT scan presented, as well as hydrocephalus, as evidenced by the plan to place an EVD. Surgical site infections (SSIs) are a common cause of healthcare-associated infections. Depending on the type of procedure performed, the Centers for Disease Control and Prevention (CDC) established criteria that define surgical site infection as infection related to an operative procedure that arises at or near the surgical incision within 30 to 90 days of the procedure. EVDs are used as a method of diverting CSF out of the cranium. Soft tissue infections and ventriculitis are the most common ventriculostomy-related infections. Reported EVD infection rates range from 0 to 32%, but an average of about 10% or less is the general consensus for the underlying rate. Before placement of the EVD, it has been routine to initiate antibiotics. However, data regarding the use of prophylactic antibiotics throughout the duration of insertion of EVDs are inconclusive at present. Gram-positive organisms are classically associated with ventriculitis, as are some reported gram-negative bacteria, but these were probably related to a nosocomial colonization caused by prolonged hospital stay. Cefazolin is an appropriate choice for prevention of drain-related infections given its narrow-spectrum coverage of specific organisms.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antibiotics; Gram-negative organisms

References

See question 12.

11. Answer: C

This patient has early-onset VAP. She does not have risk factors for infection with multidrug-resistant organisms (MDROs). VAP is defined as hospital-acquired pneumonia arising more than 48 hours after endotracheal intubation. It is further classified by the CDC as a ventilator-associated event and an infection-related ventilator-associated complication. VAP is usually caused by bacterial pathogens; the infection can be monomicrobial or polymicrobial in nature but is seldom caused by viral or fungal pathogens. The diagnosis of VAP is classified into two categories: early onset (less than 5 days from hospitalization) or late onset (5 days or more from hospitalization). Early-onset hospital-acquired pneumonia and VAP are usually community-associated organisms, including Haemophilus influenzae, methicillin-sensitive S. aureus (MSSA), S. pneumoniae, and enteric gram-negative bacilli. Atypical bacteria, such as L. pneumophila, do not commonly cause VAP, and it is not necessary to add antibiotic coverage for this class of organisms, although consideration should be given if there is a poor response to initial therapy. Late-onset VAP is often associated with MDRO infection. Patients with early-onset VAP and risk factors for MDRO should be managed similarly to patients with late-onset VAP (Box 7.1).

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antimicrobial resistance

References

See question 12.

12. Answer: A

Ceftriaxone is a reasonable agent for empiric management of early-onset VAP because it has activity against common pathogens. Broad-spectrum antibiotics, such as piperacillin-tazobactam and cefepime, would provide adequate coverage but would result in an unnecessary breadth of antibiotic exposure. In patients with suspected VAP, empiric antibiotic therapy should be initiated. To reduce the incidence of mortality, appropriate selection of antibiotic is critical. To decrease the likelihood of inappropriate therapy, empiric antibiotic selection should be based on multiple factors. First, timing of pneumonia from hospital admission can differentiate between early-onset and late-onset VAP because the pathogens involved in the disease process are not the same. Regardless VAP onset, patients should be carefully evaluated for risk factors for MDROs. Despite current recommendations, it is strongly advised to select the antibiotic based on local antibiotic susceptibility patterns because of growing concern about antibiotic resistance. Antibiotic selection should include IV agents to achieve relevant lung concentrations related to pathogen minimum inhibitory concentration (MIC) and should be dosed optimally using evidence-based pharmacokinetic and pharmacodynamic principles.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antimicrobial resistance

References

American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388–416.Find this resource:

Arabi Y, Memish ZA, Balkhy HH et al. Ventriculostomy-associated infections: incidence and risk factors. Am J Infect Control 2005;33(3):137–143.Find this resource:

Berríos-Torres SI, Umscheid CA, Bratzler DW et al. Centers for Disease Control and Prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg 2017;152(8):784.Find this resource:

Blomstedt GC. Results of trimethoprim-sulfamethoxazole prophylaxis in ventriculostomy and shunting procedures. J Neurosurg 1985;62(5):694–697.Find this resource:

Dettenkofer M, Ebner W, Els T et al. Surveillance of nosocomial infections in a neurology intensive care unit. J Neurol 2001;248(11):959–64.Find this resource:

Dey M, Stadnik A, Riad F et al. Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial. Neurosurgery 2015;76(3):291–300.Find this resource:

Klompas M, Branson R, Eichenwald EC et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35:915–936.Find this resource:

Lyke KE, Obasanjo OO, Williams MA et al. Ventriculitis complicating use of intraventricular catheters in adult neurosurgical patients. Clin Infect Dis 2001;33(12):2028–2033.Find this resource:

Zabramski JM, Whiting D, Darouiche RO et al. Efficacy of antimicrobial-impregnated external ventricular drain catheters: a prospective, randomized, controlled trial. J Neurosurg 2003;98(4):725–730.Find this resource:

13. Answer: D

Because of the history of ESBL-producing Enterobacteriaceae, the drug of choice would be meropenem. Ceftriaxone, cefepime, and piperacillin-tazobactam would not be good choices to treat the ESBL-producing organism because of resistance and reports of clinical failure. Daptomycin and vancomycin both have activity against MRSA.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antibiotics; Gram-negative organisms

References

See question 14.

14. Answer: C

The susceptibility panel reveals only intermediate susceptibility to meropenem; this alone is not a viable treatment option to avoid treatment failure. Treatment options for multidrug-resistant Acinetobacter baumannii are limited to tigecycline and polymyxins (i.e., colistin). Amikacin susceptibility is unknown in the case and therefore should not be included until further results are revealed.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antimicrobial resistance

References

Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multi-drug-resistant Pseudomonas aeruginosa. Mayo Clin Proc 2011;86:250–259.Find this resource:

Manchanda V, Sanchaita S, Singh NP. Multidrug resistant Acinetobacter. J Glob Infect Dis 2010;2:291–304.Find this resource:

Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Micro Rev 2005;18:657–686.Find this resource:

Pogue JM, Mann T, Barber KE et al. Carbapenem-resistant Acinetobacter baumannii: epidemiology, surveillance and management. Expert Rev of Anti-infect Ther 2013;11:383–393.Find this resource:

15. Answer: A

The patient presented with community acquired complicated intra-abdominal infection involving the middle small intestine. The common organisms involved with these complications include Escherichia coli and Klebsiella spp. A patient with severe disease should be broadly covered for presence of P. aeruginosa and enterococci. Piperacillin-tazobactam has empiric activity against these organisms. Anaerobic coverage is warranted if the distal small bowel and the large bowel are the sites of infection. This region is populated with anaerobic gram-negative and gram-positive organisms. Answers B and C do not have sufficiently broad coverage to include enterococci. and need for solely anaerobic coverage (with metronidazole) is not indicated in this case.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antibiotics,;Anaerobes

References

Marshall JC, Innes M. Intensive care unit management of intra-abdominal infection. Crit Care Med 2003;31:2228–2237. (In-depth descriptive review of pathophysiology and management strategies of complicated intra-abdominal infection in critically ill patients.)Find this resource:

Solomkin JS, Mazuski JE, Bradley JS et al. Diagnosis and management of complicated intraabdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010;50:133–164.Find this resource:

16. Answer: C

While results are pending, empiric therapy for both bacterial and viral encephalitis should be initiated because of the MRI results. This patient is at risk for Neisseria meningitidis and S. pneumoniae. IV acyclovir should be started for management of the most likely cause of viral encephalitis, HSV. HSV-1 is the most common virus to cause sporadic encephalitis in the United State; it is responsible for about 90% of HSV encephalitis in adults and children; HSV-2 is the etiology for the other 10%. With a mortality rate of 70% when untreated, timely administration of acyclovir improves survival and outcomes, especially when introduced early in infection. Broad-spectrum antibiotics, such as linezolid and cefepime, would provide adequate coverage but would result in an unnecessary breadth of antibiotic exposure. Cefepime in particular would be reasonable for nosocomial infection, but not for community-acquired infection, which is implied in the stem.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antibiotics; Other

References

See question 17.

17. Answer: C

HSV PCR, LP results, and radiologic evidence strongly confirm the diagnosis of HSV encephalitis. Because there is no strong indication of bacterial infection, antibiotics should be discontinued at this time. A 14-day course of acyclovir therapy is suggested in confirmed cased of HSV encephalitis. Dosing should be 10 mg/kg IV every 8 hours in the setting of good renal function. The patient should also be well hydrated while on acyclovir to prevent renal damage unless contraindicated.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antiviral

References

Mailles A, Stahl JP. Infectious encephalitis in France: a national prospective study. Clin Infect Dis 2009;49:1838–1847.Find this resource:

Tunkel AR, Glaser CA, Bloch KC et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008;47:303–327.Find this resource:

Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267–1284.Find this resource:

Whitley RJ, Kimberlin DW. Herpes simplex encephalitis: children and adolescents. Semin Pediatr Infect Dis 2005;16:17–23.Find this resource:

18. Answer: B

Doxycycline is an agent used for coverage of suspected spirochetal and rickettsial infection. Rickettsial infection is typically acquired from tick or mite bites and can be acquired anywhere in the United States, Canada, Mexico, Central America, or South America. Rocky Mountain spotted fever (RMSF) was first reported in Idaho and is the most common cause of rickettsial infection in the United States, with nearly 5000 cases reported in 2012. Linezolid and amoxicillin are distracters in this stem. The history of reflux disease with a chronic proton pump inhibitor (PPI) may appear to be related to the patient’s complaint of rash, and PPIs are associated with a mild rash following chronic treatment. Normally, withdrawal of the PPI will result in resolution of the patient’s rash within a few weeks, although this does not explain the patient’s fever, confusion, or abdominal pain.

The image in the question of a lesion (erythema and perifollicular petechiae) on the left medial upper ankle/lower calf of a patient with tick-borne spotted fever caused by Rickettsia parkeri. The earliest rash of RMSF looks similarly subtle if the clinician is fortunate enough to see the rash before the patient begins to deteriorate clinically.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antibiotics; Spirochetal and rickettsial

References

Biggs HM, Behravesh CB, Bradley KK et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis—United States. MMWR Recomm Rep 2016;65(2):1.Find this resource:

Tubiana S, Mikulski M, Becam J et al. Risk factors and predictors of severe leptospirosis in New Caledonia. PLoS Negl Trop Dis 2013;7(1):e1991.Find this resource:

Walker DH. Rickettsiae and rickettsial infections: the current state of knowledge. Clin Infect Dis 2007;45(Suppl 1):S39.Find this resource:

19. Answer: A

Although this patient has been admitted to the hospital with a trauma diagnosis, her workup to this point does not indicate an acute abdominal process. The complaint of anal itching in the setting of abdominal pain and nausea is consistent with a severe pinworm infection. The two most common nematode infections worldwide are Enterobius vermicularis (pinworm) and Trichuris trichiura (whipworm). Humans are the only natural host for Enterobius, and infection can occur in temperate and tropical climates. Enterobius is the most common helminthic infection in the United States and Western Europe, and it is believed that there are 40 million individuals infected in the United States. Trichuriasis occurs most commonly in tropical climates. The drug of choice for treating these infections is mebendazole. When mebendazole is given once initially and then again at the end of 2 weeks, the cure rate is nearly 100%. The “paddle test,” in which a spatula or something similar with adhesive is applied to the perianal area and then placed against a slide that is then examined under a microscope, is a common and easy technique for diagnosis. This patient’s presentation, consisting of nausea and abdominal pain, is particularly severe.

Keywords: Specialized areas; Pharmacology (indications, contraindications, and complications); Antimicrobials; Antiparasitic

References

Centers for Disease Control and Prevention. Enterobiasis (Enterobius vermicularis). Available at www.dpd.cdc.gov/DPDx/HTML/Enterobiasis.htm. Accessed on March 3, 2018.Find this resource:

Moore TA, McCarthy JS. Enterobiasis. In: Guerrant R, Walker DH, Weller PF, eds. Tropical infectious diseases: principles, pathogens and practice, 3rd edition. Philadelphia: Saunders Elsevier; 2011, p. 788.Find this resource:

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