Q: Acute rejection of acute lung transplant is? 

A) lymphocyte predominant inflammatory response
B) neutrophil predominant inflammatory response 
C) monocyte predominant inflammatory response
D) eosinophil predominant inflammatory response
E)  basophil predominant inflammatory response


Answer: A

Transbronchial lung biopsy is important to watch in new post lung transplant patients  as acute rejection may be clinically asymptomatic. Hallmark of acute rejection is a lymphocyte predominant inflammatory response. It should be looked for with care in biopsy report.



References: 

1.  Martinu T, Chen DF, Palmer SM. Acute rejection and humoral sensitization in lung transplant recipients. Proc Am Thorac Soc 2009; 6:54. 

2. Martinu T, Pavlisko EN, Chen DF, Palmer SM. Acute allograft rejection: cellular and humoral processes. Clin Chest Med 2011; 32:295. 

3. Haque MA, Mizobuchi T, Yasufuku K, et al. Evidence for immune responses to a self-antigen in lung transplantation: role of type V collagen-specific T cells in the pathogenesis of lung allograft rejection. J Immunol 2002; 169:1542. 

A note on Serum procalcitonin (PCT) level and Small Bowel Obstruction (SBO)

 PCT has an interesting value in SBO management. A PCT value of 0.17 ng/mL has shown to be an 85% negative predictive value for failure of nonoperative management! And similarly, a PCT value of more than or equal to 0.57 ng/mL has an 83% of positive predictive value.

Famous ABOD (Acute Bowel Obstruction Diagnosis) study 1, showed that PCT value correlates well with medically managed group, patients who require surgery and patients who are found to have ischemia during surgery.

What is of more interesting in ABOD study, lactic acid and leucocytosis were not predictive of ischemia!!


References:

1. Cosse C, Regimbeau JM, Fuks D, et al. Serum procalcitonin for predicting the failure of conservative management and the need for bowel resection in patients with small bowel obstruction. J Am Coll Surg 2013; 216:997.

2. Markogiannakis H, Memos N, Messaris E, et al. Predictive value of procalcitonin for bowel ischemia and necrosis in bowel obstruction. Surgery 2011; 149:394.

Q: All of the following direct oral anticoagulants (DOACs) have partial excretion in hepatic insufficiency, and may cause bio-accumulation in severe liver insufficiency except? 

A) Dabigatran 
B) Rivaroxaban 
C) Apixaban 
D) Edoxaban
E) Warfarin


Answer: A

All of the DOACs have renal and hepatic excretion except Dabigatran which has no hepatic metabolism

Warfarin is not a DOAC.

Q: All of the following drugs can cause adrenal inhibition in ICU except? 

 A) ketoconazole 
B) metyrapone 
C) fluconazole 
D) etomidate 
E) hydrocortisone


Answer: E

All of the above choices except choice E (hydrocortisone) are adrenal enzyme inhibitors involved in endogenous cortisol making. In fact they are used as treatment in hypercorticolism 1,2, 3. Objective of above question is to highlight other drugs beside etomidate, which has already earned enough bad name in this regard! Fluconazole is widely and many times inappropriately used in ICU and should be suspected in such clinical scenarios 4, 5

Hydrocortisone is the treatment for adrenal insufficiency in ICU.


References:

1. Jeffcoate WJ, Rees LH, Tomlin S, et al. Metyrapone in long-term management of Cushing's disease. Br Med J 1977; 2:215.

2. Loli P, Berselli ME, Tagliaferri M. Use of ketoconazole in the treatment of Cushing's syndrome. J Clin Endocrinol Metab 1986; 63:1365. Schulte HM, Benker G, Reinwein D, et al.

3. Infusion of low dose etomidate: correction of hypercortisolemia in patients with Cushing's syndrome and dose-response relationship in normal subjects. J Clin Endocrinol Metab 1990; 70:1426.

4. Gordon J D, Sepkowitz D V. Fluconazole associated acute adrenal insufficiency. Postgrad Med J 1991671084–1085.1085

5. Michaelis G, Zeiler D, Biscoping J. et al Function of the adrenal cortex during therapy with fluconazole in intensive care patients. Mycoses 199336117–123.123

Q; What is 1 x 1 rule while inserting femoral venous central line catheter?



Answer: 

Ideal location foe central venous catheter via femoral approach is 1 cm below the inguinal ligament and 1 cm medial to the femoral arterial pulsation. Apply all 3 precautions decrease the chances of complications

1. Landmark identifications
2. Palpating arterial pulsation
3. confirmation and performing procedure under ultrasound

Q: Intraarticular antibiotics should be considered as first line of therapy in severe septic arthritis?

A) True
B) False


Answer: B (False)

Actually intraarticular antibiotics are contraindicated as they may mount severe inflammatory response, and make clinical situation worse. Parenteral/oral antibiotics are capable of invading joint fluid and induce therapeutic levels.



Reference: 

Goldenberg DL, Reed JI. Bacterial arthritis. N Engl J Med 1985; 312:764.

Q: Cryoprecipitate as name applied can be kept frozen for clinical use for how long?

Answer: About one year.

Fresh-Frozen -Plasma obtained from one unit of blood is thawed at 4°C for about 24 hours, which makes precipitates of cold-insoluble proteins, which are very rich in blood coagulation factors. It is re-frozen at -18°C. Total amount of cryoprecipitate obtained from one unit of blood is about 10-15 mL. This product can be kept frozen at -18°C for about one year to use for clinical transfusions. 

Q: Out of following which drug's IV infusion in ICU does not pose threat of propylene glycol toxicity?

A) Lorazepam 
B) Diazepam
C) Midazolam


Answer:  C

Propylene glycol is the solvent used as a carrier to deliver intravenous lorazepam or diazepam infusion. Threat of high an-ion gap metabolic acidosis is always potential on patients with long term or high dose infusions. Midazolam does not require propylene glycol  as a carrier.


References:

1. Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines: a case series and prospective, observational pilot study. Chest 2005; 128:1674. 

2. Wilson KC, Reardon C, Farber HW. Propylene glycol toxicity in a patient receiving intravenous diazepam. N Engl J Med 2000; 343:815.

Q: While reviewing ECHO report of a patient, you see the word 'Cor triatriatum'. What does it mean?


Answer:  Know to physicians for 150 years, Cor triatriatum as name applied is a heart with 3 atria. It is a congenital anomaly in which either the left or right atrium is divided into 2 compartments by a membrane (or tissue fold).

If left atrium is involved it is called cor triatriatum sinistrum, and if right atrium is involved, it is called cor triatriatum dextrum.

Picture Diagnosis

Answer:  Hollenhorst plaque

Hollenhorst plaques are bright, refractile lesions in the retina.They are emboli from plaque ulceration in the internal carotid artery. Though they represent "eye stroke" but often asymptomatic and found in older individuals on routine exam.

Q: What is the FLUSH test after femoral central line insertion?



Answer:  FLUSH is an abbreviation of "Flush the Line and Ultra-Sound the Heart".

It can be used after femoral central venous line insertion to confirm intravenous placement. It can be particularly helpful in code situation where it becomes hard to distinguish between arterial and venous blood due to absence of pulsatility and absence of difference of color. 

In the test, the distal port of central venous catheter is flushed with agitated saline and the heart is visualized at a subxiphoid location via bedside ultrasound or echo machine.


Reference:

Horowitz R, Gossett JG, Bailitz J, Wax D, Pierce MC. The FLUSH study--flush the line and ultrasound the heart: ultrasonographic confirmation of central femoral venous line placement. Ann Emerg Med. 2014 Jun. 63(6):678-83.

Q: Nebulized Tobramycin has high systemic absorption, so it should be used with caution in ICU as a nebulizer treatment, and should be discontinued if creatinine goes up?

A) True
B) False


Answer:  False 

 Tobramycin except for intravenous or intramuscular route has negligible systemic absorption. There is no oral formulation available as it does not get absorb via GI tract. It is very safe to use as ophthalmic drops or as nebulised treatments.

Bonus pearls:

• Tobramycin works very well in life-threatening Yersinia pestis (plague).
• Tobramycin has better penetration in lungs over gentamicin for pseudomonas pneumonia.

.Q: At what level of creatinine, renal adjustment of apixaban (Eliquis) should be considered?



Answer: Serum creatinine more than or equal to 1.5 mg/dL

Three main category advised for dose reduction of apixaban are

• age  at 80 years or above
• body weight at 60 kg or less
• Serum creatinine 1.5 mg/dL or more

When two or more of the above present simultaneously, it became more compelling to reduce the dose. Pharmacy should be consulted for dose management to avoid undue bleeding as apixaban has no reversal available yet (still under development with name of Andexanet alfa).

Q: What does SQI means on bedside monitor while collecting hemodynamic monitoring data? 

Answer: Signal Quality Indicator 

Signal Quality Indicator as name indicates signifies the quality of electrical signal of transducers while calibrating Pulmonary Artery Catheter, particularly for SVO2 (Mixed Venous Oxygen saturation.  SQI runs from number one to number four (SQI1, SQI2, SQI3, SQI4), been SQI1 most reliable.

Calibration should not be relied on if SQI is equal to or greater than three. Some experts even take SQI2 as questionable.

Q: What are the six requisite of pathophysiology of cholesterol emboli?

Answer:

1. Presence of a plaque in a proximal, large-caliber artery (such as the internal carotid artery, the iliac arteries, or the aorta) 
2. Plaque rupture (spontaneous, traumatic, or iatrogenic) 
3.  Embolization of plaque debris (containing cholesterol crystals, platelets, fibrin, and calcified detritus) 
4.  Lodging of the emboli in small to medium arteries with a diameter of 100 to 200 μm, leading to mechanical occlusion 
5.  Foreign-body inflammatory response to cholesterol emboli 
6.  End-organ damage due to a combined effect of mechanical plugging and inflammation

Reference: 

Itzhak Kronzon, Muhamed Saric - Cholesterol Embolization Syndrome, Circulation. 2010;122:631-641 Originally published August 9, 2010

Q: Is mobilization of patients while on Continuous Renal Replacement Therapy (CRRT) is absolute contraindication?


Answer:  No

Actually, there is now literature emerging to show that early mobilization of patients while on active CRRT can be beneficial, and may improve efficacy of CRRT by increasing the filter life.


References:

1. Wang YT, Haines TP, Ritchie P, Walker C, Ansell TA, Ryan DT, et al. Early mobilization on continuous renal replacement therapy is safe and may improve filter life. Crit Care Lond Engl. 2014;18:R161. 

2.  Toonstra AL, Zanni JM, Sperati CJ, Nelliot A, Mantheiy E, Skinner EH, et al. Feasibility and safety of physical therapy during continuous renal replacement therapy in the intensive care unit. Ann Am Thorac Soc. 2016;699–704.

Q: What is Solvent/Detergent-Treated Plasma (SD Plasma)? 

 Answer: Fresh frozen plasma (FFP) despite all precautions still carry minor risk of viral transmission. The solvent/detergent (SD) is a special process by which plasma get safely inactivated all lipid-enveloped viruses. 

Clinical significance: SD plasma found to have lesser incidence of TRALI (Transfusion Related Acute Lung Injury) over FFP, as well as lower incidence of allergic reactions. It has been increasingly used in liver transplant cases.


References:

1.  Krusius T, Auvinen M-K, Tuimala Introduction of Octaplas® in clinical use decreased the rate of serious adverse reactions. Vox Sang. 2010;99(suppl 1):P-1018. 

2. Solheim BG, Bergan A, Brosstad F, Innes R, Svennevig JL. Fibrinolysis during liver transplant is enhanced by using solvent/detergent virus inactivated plasma (ESDEP/Ocatplas®) (Letter) Anesth Analg. 2003;96:1230–1231. 

3. Peter Hellsterna, and Bjarte G. Solheimb - The Use of Solvent/Detergent Treatment in Pathogen Reduction of Plasma - Transfus Med Hemother. 2011 Feb; 38(1): 65–70. Published online 2011 Jan 17.

4. Horowitz B1, Bonomo R, Prince AM, Chin SN, Brotman B, Shulman RW. - Solvent/detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma. - Blood. 1992 Feb 1;79(3):826-31. 

Q: What is the formula to anticipate excess citrate in Continuous Renal Replacement Therapy (CRRT) patient? 


Answer: Total Ca/iCa concentration

 Sodium citrate has a complex effect while CRRT. Citrate is not only an anticoagulant but a buffer generator as well as citric acid.

Na3 citrate + 3H2CO3 → citric acid (C6H8O7) + 3NaHCO3

Secreted citric acid mostly get metabolized in liver's mitochondria which may decreased in liver insufficiency. If citrate accumulates,  Ionized calcium (iCa) decreases and metabolic acidosis ensues (because bicarbonate continues to be removed by CRRT). Accumulation of citrate due to decreased metabolism can be predicted by ratio

 Total Ca/iCa concentration

A ratio of more than 2.1 or 2.5 is c/w a citrate concentration of greater than 1 mmol/l.

Also clinically, Citric acid accumulation cause increased anion gap metabolic acidosis.

Same formula can be applied in patients receiving a massive transfusion, as blood products contain substantial amount of sodium citrate.



References: 

1.  Bakker AJ, Boerma EC, Keidel H, Kingma P, van der Voort PH. Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium. Clin Chem Lab Med. 2006;44:962–966. 

2. Meier-Kriesche HU, Gitomer J, Finkel K, DuBose T. Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation. Crit Care Med. 2001;29:748–752

Q: In necrotising fasciitis/myositis, which of the following is most reliable/sensitive? 

A) Plain x-ray 
B) CT scan without contrast 
C) MRI 
D) Ultrasound 
E) PET scan


Answer: B

Contrary to expectation, MRI is not as useful as CT scan without contrast in the diagnosis of necrotising fasciitis/myositis as MRI's over sensitivity overestimates deep tissue involvement and cannot provide demarcation between necrotizing cellulitis and deeper infection!

Ultrasound lacks sensitivity as soft tissue swelling from any cause is hard to distinguish from necrotising etiology.

PET scan has no role in the diagnosis of necrotising fasciitis/myositis, and is used by autor of this MCQ to fill up five choices :)

Clinical exam and surgical approach is still the gold standard in the diagnosis of necrotising fasciitis/myositis.



References:

1. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis 2007; 44:705.

2. Zacharias N, Velmahos GC, Salama A, et al. Diagnosis of necrotizing soft tissue infections by computed tomography. Arch Surg 2010; 145:452. 

3. Schmid MR, Kossmann T, Duewell S. Differentiation of necrotizing fasciitis and cellulitis using MR imaging. AJR Am J Roentgenol 1998; 170:615.

Q: How much change in level of hemoglobin should necessitate adjustment on bedside monitor to obtain accurate hemodynamic data from Pulmonary Artery Catheter (PAC/Swan-Ganz Catheter)?


Answer: A change in hemoglobin of 1.8 g/dL or greater should compel change/update  in the record of hemoglobin on the bedside monitor. In any case, by default a calibration of transducers/monitor/PAC should be performed at least once every 24 hours.

Q: What is the pitfall in diagnosing abdominal compartment syndrome in postpartum hemorrhage patients? 


 Answer: Post C-section, the normal postpartum patient may have an intra-abdominal pressure (bladder pressure) as equal to pregnant patients with true intra-abdominal hypertension (IAH), also known as intra-abdominal compartment syndrome. This may lead to ignore or misdiagnosed IAH secondary to postpartum hemorrhage.


Reference: 

 Abdel-Razeq SS, Campbell K, Funai EF, et al. Normative postpartum intraabdominal pressure: potential implications in the diagnosis of abdominal compartment syndrome. Am J Obstet Gynecol 2010; 203:149.e1.

Q: To diagnose perforated peptic ulcer disease PUD), if water soluble oral contrast is given 

 A) Patient should be rotated 360 degrees and placed on the right side 
B) Patient should be rotated 360 degrees and placed on the left side 
C) Patient should be rotated 180 degrees and placed on the right side 
D) Patient should be rotated 180 degrees and placed on the left side 
E) KUB should be obtained 30 minutes after oral contrast in lordotic position 


 Answer: A

In this era of rapid CT scan, many old previous techniques have been forgotten, but they are cost effective, or at least academically should be known to a physician. In perforated PUD, free air in KUB is very diagnostic but it may be missing in one fifth of the cases. One other technique to confirm perforated PUD is to find  leakage of water soluble oral contrast. After administrating water soluble oral contrast, patient should be rotated 360 degrees and placed on the right side to fill the antrum and duodenum, and to document leakage.


References:

1. Wong CH, Chow PK. Posterior perforation of gastric ulcer. Dig Dis Sci 2004; 49:1882. 

2. Grassi R, Romano S, Pinto A, Romano L. Gastro-duodenal perforations: conventional plain film, US and CT findings in 166 consecutive patients. Eur J Radiol 2004; 50:30. 

3. Donovan AJ, Berne TV, Donovan JA. Perforated duodenal ulcer: an alternative therapeutic plan. Arch Surg 1998; 133:1166.

Q: In ICU, out of the following, which ethnic group may be seen with higher than usual doses of antidepressants?

A) African Americans 
B) Asian Americans 
C) Ethiopians (blacks) 
D) Saudi Arabians 
E) Whites Americans


Answer: C

Pharmacogenetics plays an important role in obtaining therapeutic level in patients. Ethnic/genetic origin plays a crucial role as some groups may require higher than normal doses to reach therapeutic level . When it comes to antidepressants, Ethiopians (blacks) can have up to 29 percent of increased CYP2D6 metabolism. In contrast, African Americans have only 5 percent and White Americans have about 4 percent of increased CYP2D6 metabolism. People originating from Saudi Arabia can also have very high increased CYP2D6 metabolism, up to 20 percent. Interestingly, Asian Americans are rarely seen to have increased CYP2D6 metabolism.


References: 

D'Empaire I, Guico-Pabia CJ, Preskorn SH. Antidepressant treatment and altered CYP2D6 activity: are pharmacokinetic variations clinically relevant? J Psychiatr Pract 2011; 17:330.

Q: In case of  overdose or bleeding secondary to Dabigatran, all of the following can be parts of management except? 

 A) tranexamic acid (antifibrinolytics) 
B) activated charcoal 
C) hemodialysis 
D) idarucizumab 
E) prothrombin complex concentrate (aPCC) 
F) idarucizumab + aPCC


Answer: F


Dabigatran is the only out of all direct oral anticoagulants (DOACs) which has reversal available, as well as it is dialysable (choice C). 

Idarucizumab (choice D) consists of humanized dabigatran-specific (Fab) antibody fragments (kind of Digibind!!). 

All other choices (A, B, E) are standards of treatment in life-threatening bleeding or overdoses secondary to DOACs. 

As idarucizumab is so new, data on its prothrombic property is extremely limited, and  aPCCs itself is very prothrombotic. Combining both of these can itself be very life threatening (Choice F) on the other end of the spectrum.


References:

1. Schiele F, van Ryn J, Canada K, et al. A specific antidote for dabigatran: functional and structural characterization. Blood 2013; 121:3554.

2. Chai-Adisaksopha C, Hillis C, Lim W, et al. Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review. J Thromb Haemost 2015; 13:1790.

Q: Ketoconazole is considered as first line of medical treatment for Cushing's syndrome. In ICUs what could be the biggest pitfall which may make this therapy ineffective? 


 Answer: Most ICU patients are by default on Gastrointestinal(GI) prophylaxis. Ketoconazole requires an acidic environment for absorption after oral intake. With the use of proton pump inhibitors (PPIs), antacids and H2 blockers, ketoconazole may become ineffective. All GI prophylaxis should be preferably discontinued if ketoconazole get used for the treatment of Cushing's syndrome. Usual dose of ketoconazole is 400-600 mg daily in divided doses, but can be used up to 1200 mg in divided doses daily. Ideally, all such therapies should be performed under the guidance of endocrinologists. 


Reference: 

Ogawa R, Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet 2010; 49:509.

Q: If bacterial/Septic arthritis is the presenting sign of infective endocarditis, what should be ruled out first?


 Answer: History of IV drug abuse

If septic arthritis is the presenting sign of infective endocarditis (IE), it is most likely due to IV drug abuse (IVDA), proved otherwise. In other words, if a patient known with IVDA, presents with bacterial arthrtis, it is mandatory to rule out IE. Most likely bugs in this scenario are staphylococcus aureus, enterococci, or streptococci. Again, any patient, who grew these bugs should be ruled out for IE.



Reference: 

 Sapico FL, Liquete JA, Sarma RJ. Bone and joint infections in patients with infective endocarditis: review of a 4-year experience. Clin Infect Dis 1996; 22:783.

Q; Ceftaroline fosamil is relatively a new cephalosporin antibiotic. It targets which resistant bacteria? 


Answer: Methicillin-resistant Staphylococcus aureus (MRSA)

Ceftaroline is relatively a new cephalosporin with particular target activity against MRSA, ansd is recommended for use in complicated skin and skin structure infections. Also, it can be used in community-acquired bacterial pneumonia. It continue to retain the broad-spectrum activity against Gram-negative bacteria.

Clinically, it has unique advantage of synergism with Daptomycin in complicated MRSA infection of skin and deep tissue structures.


References:

1. R, Corey; Wilcox M; Talbot GH; et al. CANVAS-1: Randomized, Double-blinded, Phase 3 Study (P903-06) of the Efficacy and Safety of Ceftaroline vs. Vancomycin plus Aztreonam in Complicated Skin and Skin Structure Infections (cSSSI). 2008 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference.

2. Kanafani ZA, Corey GR (February 2009). "Ceftaroline: a cephalosporin with expanded Gram-positive activity". Future Microbiology. 4: 25–33.

3.  Parish D, Scheinfeld N (February 2008). "Ceftaroline fosamil, a cephalosporin derivative for the potential treatment of MRSA infection". Current Opinion in Investigational Drugs (London, England : 2000). 9 (2): 201–9 

4. "Forest Announces FDA Approval of Teflaro(TM) (ceftaroline fosamil) for the Treatment of Community-Acquired Bacterial Pneumonia and Acute Bacterial Skin and Skin Structure Infection" (Press release). Forest Laboratories. 2010-10-29. Retrieved October 30, 2010. 

5. Sakoulas G, Moise PA, Casapao AM, Nonejuie P, Olson J, Okumura CY, Rybak MJ, Kullar R, Dhand A, Rose WE, Goff DA, Bressler AM, Lee Y, Pogliano J, Johns S, Kaatz GW, Ebright JR, Nizet V - Antimicrobial salvage therapy for persistent staphylococcal bacteremia using daptomycin plus ceftaroline. - Clin Ther. 2014 Oct 1;36(10):1317-33.

Q: How dialysis mode is different from filtration in renal therapy?

Answer: 

Dialysis  means - diffusion-based solute removal
Filtration means -  convection-based solute and water removal

Dialysis is easy to understand as a solute passively diffuses via concentration gradient.

Filtration is an interesting (convection) phenomenon where the frictional forces between water and solutes, results in the  transport of small and middle molecular weight solutes along with water (kind of drag on phenomenon). 

Q: What is the advantage of the use of regional citrate in acute kidney injury (AKI) over other modes of anticoagulation? 

 Answer: Regional citrate has shown to increase the chances of kidneys to recover from acute injury. Exact mechanism is not confirmed but probably it is due to ability of citrate to reduce inflammation by inhibiting calcium-dependent activation of neutrophils and platelets.


References:

1. Gritters M, Grooteman MP, Schoorl M, et al. Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis. Nephrol Dial Transplant 2006; 21:153. 

2. Böhler J, Schollmeyer P, Dressel B, et al. Reduction of granulocyte activation during hemodialysis with regional citrate anticoagulation: dissociation of complement activation and neutropenia from neutrophil degranulation. J Am Soc Nephrol 1996; 7:234.