Modified CCI

Q: All of the following are part of modified Charlson Comorbidity Index (CCI) EXCEPT? 

A) Heart failure 

B) Diabetes 

C) Renal insufficiency

D) Solid tumor 

E) Depression

Answer: E

Charlson comorbidity index (CCI) - modified - is mostly used in oncology patients to determine physiologic fitness, which is different from performance status. CCI is more oriented toward the severity of comorbid conditions. This helps in determining the treatment regimen for the patients. It divides patients into three categories 

• Medically fit: with CCI score of 0 to 2 
• Medically-unfit, but not frail: with CCI score of 3 
• Frail: Score above 3 

Comorbidities with single points are myocardial infarction (MI), heart failure, cerebrovascular disease, ulcer, mild hepatic disease, mild or moderate diabetes, moderate or severe pulmonary disease, and connective tissue disease. 

Severe diabetes with end-organ damage, moderate or severe renal disease, solid tumor without metastases carries 2 points each. 

Moderate to severe hepatic disease gets 3 points. Solid tumor with metastases gets the highest points - 6.

Depression is not included in CCI (choice E)

#oncology

Reference:

Etienne, A, Esterni, B, Charbonnier, A, et al. Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer 2007; 109:1376. Copyright © 2007 American Cancer Society. 

ANC

 Q: How the absolute neutrophil count (ANC) is calculated? 

Answer: The definition of Neutropenia is an absolute neutrophil count (ANC) of less than 1500/microL.

The formula to calculate ANC is 

 ANC = WBC (cells/microL) x percent (PMNs + bands) ÷ 100 

The objective of this question is to highlight the fact that both polymorphonuclear cells (PMNs) and band forms from the differential should be used to obtain accurate ANC.

#hematology

Reference:

Al-Gwaiz LA, Babay HH. The diagnostic value of absolute neutrophil count, band count and morphologic changes of neutrophils in predicting bacterial infections. Med Princ Pract. 2007;16(5):344-7. doi: 10.1159/000104806. PMID: 17709921.

livedo reticularis and livedo racemosa

 Q: What is the difference between livedo reticularis and livedo racemosa? 

 Answer:

Livedo reticularis is a violaceous mottling or reticular pattern of the skin of the arms and legs with regular unbroken circles. 

And, if on examination circles appear irregular and broken it is called livedo racemosa.

 Please see reference section for review articles 

#rheumatology

References:

1. Sajjan VV, Lunge S, Swamy MB, Pandit AM. Livedo reticularis: A review of the literature. Indian Dermatol Online J. 2015;6(5):315-321. doi:10.4103/2229-5178.164493 

2. Pincelli MS, Echavarria AMJ, Criado PR, Marques GF, Morita TCAB, Valente NYS, de Carvalho JF. Livedo Racemosa: Clinical, Laboratory, and Histopathological Findings in 33 Patients. Int J Low Extrem Wounds. 2021 Mar;20(1):22-28. doi: 10.1177/1534734619896938. Epub 2020 Jan 29. PMID: 31996060.

MDR, XDR, and PDR

 Q: What is the difference between MDR, XDR, and PDR bacteria susceptibility to antibiotics?

Answer:

Multi-drug resistant (MDR): refer to bacteria that acquire nonsusceptibility to at least one agent in three different antimicrobial classes. 

Extensively drug-resistant (XDR): refers to bacteria that acquire nonsusceptibility to at least one agent in all but two antimicrobial classes. 

Pandrug resistant (PDR): refers to bacteria that acquire nonsusceptibility to all antimicrobial agents.

#ID

References:

Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268.

anti-proteinuria

 Q: Which of the following group of drugs has the best anti-proteinuria effect? (select one)

A) calcium channel blockers 

B) beta-blockers 

C) diuretics 

D) alpha-1-blockers 

 E) methyldopa

Answer: A

Although ACE inhibitors and Angiotensin II receptor blockers (ARBs) are known as anti-proteinuria agents and are used as a standard in diabetic patients. In addition, non-dihydropyridine calcium channel blockers (diltiazem, verapamil) has a good antiproteinuric effect. 

Beta-blockers, diuretics, and alpha-1-blockers have some antiproteinuric effects but methyldopa has little effect on protein excretion.

#pharmacology

References:

1. Bakris GL, Weir MR, Secic M, et al. Differential effects of calcium antagonist subclasses on markers of nephropathy progression. Kidney Int 2004; 65:1991. 

2. Ruggenenti P, Perna A, Benini R, Remuzzi G. Effects of dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibition, and blood pressure control on chronic, nondiabetic nephropathies. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). J Am Soc Nephrol 1998; 9:2096.

3. Gansevoort RT, Sluiter WJ, Hemmelder MH, et al. Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials. Nephrol Dial Transplant 1995; 10:1963. 

Austrian's syndrome

 Q: What is Austrian's syndrome?

Answer: Although Austrian's syndrome was first described by Osler in 1881, it is named after Dr. Robert Austrian who described it in more methodological manner in 1957. Contrary to popular belief it has nothing to do with the country Austria.

It is a clinical triad consisting of 

•  pneumococcal endocarditis 
• meningitis
•  pneumonia 

The aortic valve is commonly and acutely involved, and interestingly infection occurs on a morphologically and functionally normal valve.

 Alcoholic patients are more prone to it. 

#ID

#cardiology

References:

1. AUSTRIAN R. Pneumococcal endocarditis, meningitis, and rupture of the aortic valve. AMA Arch Intern Med 1957; 99:539. 

2. Gransden WR, Eykyn SJ, Phillips I. Pneumococcal bacteraemia: 325 episodes diagnosed at St Thomas's Hospital. Br Med J (Clin Res Ed) 1985; 290:505. 

3. Aronin SI, Mukherjee SK, West JC, Cooney EL. Review of pneumococcal endocarditis in adults in the penicillin era. Clin Infect Dis 1998; 26:165.

torsemide

 Q: What advantage torsemide has over furosemide? 

Answer: Predictable bioavailability

Oral torsemide has high and reliable bioavailability. This can be of advantage in ICU while converting intravenous meds to the oral route. Bumetanide has the same advantage. 

In contrast, the bioavailability of oral furosemide is almost half. Also, the response of oral furosemide can't be predicted. Interestingly, response varies in the same patient from dose to dose.

#phamacology

#nephrology

#cardiology

References:

1. Abraham B, Megaly M, Sous M, Fransawyalkomos M, Saad M, Fraser R, Topf J, Goldsmith S, Simegn M, Bart B, Azzo Z, Mesiha N, Sharma R. Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure. Am J Cardiol. 2020 Jan 1;125(1):92-99. doi: 10.1016/j.amjcard.2019.09.039. Epub 2019 Oct 10. PMID: 31699358.

2. Kaojarern S, Day B, Brater DC. The time course of delivery of furosemide into urine: an independent determinant of overall response. Kidney Int 1982; 22:69. 

3. Cohen N, Dishi V V, Zaidenstein R, Soback S, Weissgarten J, Averbukh Z, Gips M, Blatt A, Berman S, Modai D, Golik A. Effects of Various Modalities of Oral Furosemide Administration in Mild or Severe Congestive Heart Failure. J Cardiovasc Pharmacol Ther. 1996 Oct;1(4):271-278. doi: 10.1177/107424849600100402. PMID: 10684427.

DRESS

 Q: All of the following are components of DRESS syndrome EXCEPT? 

 A Fever 

B) Eosinophilia 

C) Monocytosis 

D) Skin rash

E) Organ involvement

Answer: C

DRESS syndrome stands for drug reaction with eosinophilia and systemic symptoms (DRESS). Criteria to diagnose DRESS syndrome is mostly based on clinical and laboratory grounds. Score includes 

• Fever 
• Enlarged lymph nodes - at least two different body sites 
• Eosinophilia 
• Atypical lymphocytes 
• Skin involvement 
• Organ involvement 
• Resolution takes more than 15 days 

A value between -1 and 2 is assigned to each feature. 

Score:

• less than 2: Excluded 
• 2 to 3: Possible 
• 4 to 5: Probable 
• 6 or above: Definite

It also requires exclusion of other causes such as HAV, HBV, HCV, mycoplasma, chlamydia, ANA, and negative blood cultures. 

 #pharmacology

References:

1. Kardaun SH, Sidoroff A, Valeyrie-Allanore L, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 2007; 156:609. 

2. Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol 2013; 169:1071.

Pulse Ox and diabetes

 Q:  Pulse-oximetry reading in a poorly controlled diabetic patient would be falsely? (select one)

A) high

B) low

Answer: A 

Diabetic patients with glycohemoglobin A1c (HbA1C) higher than 7 may falsely read pulse ox's arterial oxygen saturation (SaO2) high. This is due to high hemoglobin oxygen affinity. 

The pulse ox's modus operandi is based on Beer-Lambert law. According to this law: "absorption of light of a given wavelength passing through a non-absorbing solvent, which contains an absorbing solute, is proportional to the product of the solute concentration, the light path length, and an extinction coefficient." 

The higher the HbA1C, the higher is the reading of the solute concentration.

#hematology

References:

1. Pu LJ, Shen Y, Lu L, et al. Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes. Cardiovasc Diabetol 2012; 11:110.

2. Jubran A. Pulse oximetry. Intensive Care Med 2004; 30:2017.

3. Bongard F, Sue D. Pulse oximetry and capnography in intensive and transitional care units. West J Med 1992; 156:57.

Scombroidosis

 Q: A group of physicians attending a medical conference has been admitted to ICU - a couple of them intubated - after having a seafood dinner together and developing severe anaphylaxis type reactions. History and cluster presentation led to the diagnosis of Scombroidosis. The major cause of the scombroid syndrome is uncooked fish? 

A) True 

B) False 

Answer: B 

The other name for scombroidosis or scombroid syndrome is histamine fish poisoning. This usually occurs within an hour or so after ingesting the spoiled finned fish. This includes tuna, mahi mahi, sardines, anchovies, herring, and others. 

This is secondary to high histamine content in the spoiled fish. Interestingly, even proper cooking does not reduce the histamine level in an already spoiled fish. The growth of bacteria in an spoiled fish meat decarboxylate the amino acid L-histidine to histamine. 

Although symptoms are similar to anaphylaxis, it is not a true anaphylaxis reaction. It can be distinguished from true allergy by measuring serum-specific IgE to the implicated fish. The other way is to obtaining a sample of spoiled fish and perform a dermal test in patients and controlled.

#toxicology

#allergy

References:

1. Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J 2020; 13:100472. 

2. Hungerford JM. Scombroid poisoning: a review. Toxicon 2010; 56:231.

3. Kelso JM, Lin FL. Skin testing for scombroid poisoning. Ann Allergy Asthma Immunol 2009; 103:447.

GI flora in GVHD

 A note on the role of Gastrointestinal Flora in Graft vs Host Disease (GVHD) 

There is a continuous and an increased interest on the role lower gastrointestinal (GI) tract bacterial microbiome plays in the development of GVHD. It is proposed that by modifying GI bacterial flora in peri-transplant period, GVHD can be prevented - as GVHD has been found to be associated with the increase pro-inflammatory bacteria, decrease anti-inflammatory bacteria, and less bacterial diversity in GI tract. 

At least one recent study comprising of 8767 fecal samples from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at four major centers showed that alterations of the lower GI microbiome i.e., loss of diversity is associated with increased mortality from GVHD  4. Some preliminary work (disclaimer: weak evidence) shows that prophylactic use of quinolone may help in preventing GVHD. This prophylactic quinolone (like ciprofloxacin) can be started a day prior to the initiation of the preparatory regimen and continue till patient is engrafted or started on IV antibiotics.

#tranplantation

References:

1. Taur Y, Jenq RR, Perales MA, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 2014; 124:1174. 

2. Holler E, Butzhammer P, Schmid K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2014; 20:640. 

3. Beelen DW, Elmaagacli A, Müller KD, et al. Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial. Blood 1999; 93:3267. 

4. Peled JU, Gomes ALC, Devlin SM, et al. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med 2020; 382:822.

Calcium repletion in liver insuff

 Q: In the presence of liver insufficiency, which one is preferred? (select one)

A) Calcium chloride 

B) Calcium gluconate

Answer: A

Calcium chloride does not require normal hepatic function to release ionized calcium into the blood. In contrast, the metabolism of calcium gluconate gets inhibited in liver insufficiency resulting in  slower ionized calcium release in blood.  

Said that care should be taken as calcium chloride carries 3 times more elemental calcium than calcium gluconate and aggressive repletion may lead to hypercalcemia.

#electrolytes

#hepatology

References:

1. British Committee for Standards in Haematology, Stainsby D, MacLennan S, et al. Guidelines on the management of massive blood loss. Br J Haematol 2006; 135:634.

2. Martin TJ, Kang Y, Robertson KM, Virji MA, Marquez JM. Ionization and hemodynamic effects of calcium chloride and calcium gluconate in the absence of hepatic function. Anesthesiology. 1990 Jul;73(1):62-5. doi: 10.1097/00000542-199007000-00010. PMID: 2360741.

3. Chakraborty A, Can AS. Calcium Gluconate. [Updated 2021 Jul 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557463/

PEEP and compliance

 Q: Positive End Expiratory Pressure (PEEP) _____________ the lung compliance (select one)

A) decreases 

B) increases 

Answer: B

In the diseased lungs, functional residual capacity (FRC) is decreased. FRC as the name applies is the air volume that stays in the lung at the end of expiration. It is determined by the elasticity of the alveoli and chest wall. 

PEEP increases the surface area by reopening the collapsed alveoli. The already partially inflated lung requires less volume and energy in subsequent breaths. This improves compliance. 

Said that, it requires a determination of "optimum PEEP" to find the best compliance.

#ventilators

References:

1. Smith TC, Marini JJ. Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction. J Appl Physiol (1985). 1988 Oct;65(4):1488-99. doi: 10.1152/jappl.1988.65.4.1488. PMID: 3053583.

2. Ben Azzouz, R.; Kumba, C.; Itani, O.; Massaut, J. Effect of PEEP on pulmonary compliance and functional residual capacity in cardiac sugery patients during the postoperative period European Journal of Anaesthesiology: June 2004 - Volume 21 - Issue - p 80 European Journal of Anaesthesiology: June 2004 - Volume 21 - Issue - p 80

Kveim-Stilzbach test

Case: 34 years old female is admitted to ICU with heart blocks. Patient has multiple previous admissions with multiple different symptoms. A plethora of workups showed mixed results. Underlying sarcoidosis is suspected but never proven. Consultant suggest Kveim-Stilzbach test. 

Answer: The Kveim-Stilzbach test is utilized in suspected cases of sarcoidosis. Its best utility lies in distinguishing sarcoidosis from otherwise indistinguishable symptoms such as in berylliosis. This is also known as Nickerson-Kveim or simply as Kveim test, named after a Norwegian pathologist who suggested the test 8 decades ago. American physician named Stilzbach modified the test with the use of spleen tissue.

The test is performed by taking a suspension from the spleen or a lymph node of a patient with a confirmed diagnosis of sarcoidosis and injecting intradermally into a patient under diagnosis. If a nodule appears within 6 weeks, a test is considered positive. To confirm further, a biopsy can be performed of the nodule to find a non-caseating granuloma. Steroids can turn test false negative. 

Said that, this test is more of academic interest as it is time and labor-consuming, may yield false negative or positive results, and may transfer infections.

#rheumatology

References:

1. Kveim MA (1941). "En ny og spesifikk kutan-reaksjon ved Boecks sarcoid. En foreløpig meddelelse". Nordisk Medicin (in Norwegian). 9: 169–172. 

2. Siltzbach LE, Ehrlich JC (1954). "The Nickerson-Kveim reaction in sarcoidosis". Am. J. Med. 16 (6): 790–803. doi:10.1016/0002-9343(54)90443-X. PMID 13158367. 

3. Williams R, Nickerson D (1935). "Skin reactions in sarcoid". Proc. Soc. Exp. Biol. Med. 33 (3): 402–405. doi:10.3181/00379727-33-8388P. 

4. Cooper, Ross G.; Harrison, Adrian P. (August 2009). "The uses and adverse effects of beryllium on health". Indian Journal of Occupational and Environmental Medicine. 13 (2): 65–76. doi:10.4103/0019-5278.55122. PMC 2847329. PMID 20386622.

Central lines and thrombosis

 Q: Subclavian central lines have the lowest rate of venous thrombosis.

A) True

B) False

Answer: A

There are many delayed complications of central lines. One of such complications is venous thrombosis. Subclavian (SC) central lines have the lowest rate of thrombosis. In contrast, femoral lines have the highest rate of thrombosis. On the other hand, SC central lines may lead to superior vena caval syndrome though incidence is pretty low at 1:1000. 

Another known delayed complication of SC central lines is catheter fracture which may lead to endocarditis/sepsis, cardiac arrhythmia or perforation. While removing central line, it should be made certain that all parts of the catheter is removed.

#procedures

References:

1. Kornbau C, Lee KC, Hughes GD, Firstenberg MS. Central line complications. Int J Crit Illn Inj Sci. 2015 Jul-Sep;5(3):170-8. 

2. Kusminsky RE. Complications of central venous catheterization. J Am Coll Surg. 2007 Apr;204(4):681-96. 

3. Deere M, Singh A, Burns B. Central Venous Access of The Subclavian Vein. [Updated 2021 Sep 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482224/

Risk of HIV

 Q: While putting an arterial line in an HIV patient blood splashed on the resident's arm. Intact skin is an effective barrier against HIV infection. 

A) True 

B) False

Answer: A

Most HIV risks come from a breach of skin. Intact skin is an effective barrier against HIV infection. Exposure to blood with intact skin does not require post-exposure prophylaxis (PEP). Moreover, stool, urine saliva, sputum, sweat, tears, urine, or vomitus are not a risk for HIV even with a breach in the skin as far there is no blood is involved. 

Besides blood - semen, vaginal secretions, CSF, pleural, peritoneal, pericardial, and amniotic fluids are considered hazardous with a breach in skin integrity.

#ID

References:

1. Panlilio AL, Cardo DM, Grohskopf LA, et al. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005; 54:1. 

2. Kuhar DT, Henderson DK, Struble KA, et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol 2013; 34:875.

BP cuff sizes

 Q: In a morbidly obese patient, an"adult thigh" cuff can be applied to arm for blood pressure measurement if arm circumference is above 44 cm?

A) True

B) False

Answer: A

If arterial line is not present, blood pressure measurement via cuff is still a standard of care in ICU. Said that this may give a wrong reading in obese patients. Smaller size cuff may give erroneously higher systolic blood pressure. By definition the length of the BP cuff bladder should be 80 percent, and the width at least 40-45 percent of the circumference of the upper arm. 

 The American Heart Association has designated a guideline of different cuffs per arm circumferences. 

• Arm circumference 22 to 26 cm, "small adult" cuff, 12 x 22 cm
• Arm circumference 27 to 34 cm, "adult" cuff, 16 x 30 cm 
• Arm circumference 35 to 44 cm, "large adult" cuff, 16 x 36 cm 
• Arm circumference 45 to 52 cm, "adult thigh" cuff, 16 x 42 cm

#hemodynamic

References:

1. Muntner P, Shimbo D, Carey RM, et al. Measurement of Blood Pressure in Humans: A Scientific Statement From the American Heart Association. Hypertension 2019; 73:e35. 

2. ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens 2013; 31:1925. 

3. Beevers G, Lip GY, O'Brien E. ABC of hypertension. Blood pressure measurement. Part I-sphygmomanometry: factors common to all techniques. BMJ 2001; 322:981. 

4. Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation 2005; 111:697.

Quetiapine and LFTs

 Q; 82 years old male was admitted to ICU with septic shock, and is now recovering. Pressors are off and patient is extubated. Patient has been started on Quetiapine for mild delirium 4 days ago. Mild elevation of transaminases and bilirubin noted. Quetiapine should be continued as far as QTc interval is normal on EKG? 

A) True 

B) False

Answer: B

Hepatotoxicity from quetiapine can be fatal. It is as important to follow as QTc interval. Although it is a rare complication but any deterioration in Liver Function Test (LFT) should be taken seriously. It can occur with a regular dose of 25 mg and with a short term use of 7-10 days 

The benign side-effects from quetiapine are dry mouth, sedation, somnolence, dizziness, fatigue, and constipation.

#toxicity

#hepatology

#pharmacology

References:

1. Shpaner A, Li W, Ankoma-Sey V, Botero RC. Drug-induced liver injury: hepatotoxicity of quetiapine revisited. Eur J Gastroenterol Hepatol 2008; 20:1106. 

2. El Hajj I, Sharara AI, Rockey DC. Subfulminant liver failure associated with quetiapine. Eur J Gastroenterol Hepatol 2004; 16:1415. 

3. Naharci MI, Karadurmus N, Demir O, et al. Fatal hepatotoxicity in an elderly patient receiving low-dose quetiapine. Am J Psychiatry 2011; 168:212.

ITP workup

 Q; 68 years old recent immigrant from South East Asian region is admitted to ICU with gastrointestinal (GI) bleed. Subsequent workup led to the diagnosis of Immune Thrombocytopenia (ITP) All of the following tests are appropriate on this patient EXCEPT? 

A) peripheral blood smear 

B) HIV 

C) Hepatitis C (HCV) 

D) Helicobacter pylori 

E) Bone marrow examination

Answer: E

Routine bone marrow biopsy is not a part of initial ITP workup, as elderly patients with ITP do not have a higher incidence of myelodysplastic syndrome (MDS). Also, it does not help to identify the cause of ITP. 

Peripheral blood smear (choice A) should be requested to rule out pseudothrombocytopenia due to clumping of platelets. 

HIV (choice B) and HCV (choice C) are now recommended as part of workup for ITP as it can be a presenting sign for both conditions. 

Helicobacter pylori (choice D) should be carried out in all individuals from endemic area due to association between H. pylori infection and ITP.

#hematology

References:

1. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117:4190. 

2. Stasi R, Sarpatwari A, Segal JB, et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood 2009; 113:1231. 

3. Vishnu P, Duncan J, Connell N, et al. International survey on Helicobacter pylori testing in patients with immune thrombocytopenia: Communication of the platelet immunology scientific and standardization committee. J Thromb Haemost 2021; 19:287.

4. Jubelirer SJ, Harpold R. The role of the bone marrow examination in the diagnosis of immune thrombocytopenic purpura: case series and literature review. Clin Appl Thromb Hemost 2002; 8:73. 

dexamethasone in brain tumor

 Q: Why dexamethasone is a drug of choice to decrease vasogenic edema from primary and metastatic brain tumors?

Answer: The objective of this question is to highlight the fact that dexamethasone doesn't only work through its anti-inflammatory effect but also has direct mechanisms to reduce tumor-induced edema. It works via various direct mechanisms:

• it upregulates Ang-1, a strong blood-brain barrier-stabilizing factor. Brain tumor tends to disrupt the blood-brain barrier.
• it downregulates vascular endothelial growth factor (VEGF) - a strong permeabilizing factor, in astrocytes and pericytes. 
• it is found to inhibit the production of interleukin 1 from tumor-associated macrophages in glioblastoma models.

#oncology

#pharmacology

References:

1. Kim H, Lee JM, Park JS, et al. Dexamethasone coordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier. Biochem Biophys Res Commun 2008; 372:243. 

2. Herting CJ, Chen Z, Maximov V, et al. Tumour-associated macrophage-derived interleukin-1 mediates glioblastoma-associated cerebral oedema. Brain 2019; 142:3834.

Acetaminophen and BP

Q: Intravenous (IV) acetaminophen may decrease the blood pressure (BP) up to the point that it may require pressor? 

A) True 

B) False

Answer: A

Acetaminophen has different effects with oral and IV routes. Chronic oral ingestion of acetaminophen has been shown to increase the baseline blood pressure and risk for chronic kidney disease. In contrast, IV acetaminophen has been shown to decrease BP in ICU patients up to the point where pressor may be required to salvage the drop in BP. 

This acetaminophen-induced hypotension can be seen within 30 minutes of administration and may last up to an hour. This effect is reproducible in non-ICU relatively healthy patients. This decrease in BP is both due to analgesic as well as a direct effect.

#hemodynamic

#pharmacology

References:

1. Cantais A, Schnell D, Vincent F, et al. Acetaminophen-Induced Changes in Systemic Blood Pressure in Critically Ill Patients: Results of a Multicenter Cohort Study. Crit Care Med 2016; 44:2192. 

2. Chiam E, Weinberg L, Bailey M, et al. The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial. Br J Clin Pharmacol 2016; 81:605. 

3. Maxwell EN, Johnson B, Cammilleri J, Ferreira JA. Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature. Ann Pharmacother 2019; 53:1033.

Sepsis and calcium

 Q: Sepsis tends to do (select one)

A) Hypocalcemia

B) Hypercalcemia

Answer: A

Hypocalcemia is more common in ICU. Patients with sepsis, burn, any other severe illness, or after surgery may develop clinically significant hypocalcemia. There are various complex mechanisms involved simultaneously. 

There is a decreased secretion of Parathyroid hormone (PTH) and calcitriol. These patients also manifest end-organ resistance to PTH due to hypomagnesemia and inflammatory cytokines on the parathyroid glands, kidneys, and bone. It has also been suggested that these patients may have high serum calcitonin concentrations which lead to inhibit bone resorption.

#electrolytes

References:

1. Zivin JR, Gooley T, Zager RA, Ryan MJ. Hypocalcemia: a pervasive metabolic abnormality in the critically ill. Am J Kidney Dis 2001; 37:689. 

2. Desai TK, Carlson RW, Geheb MA. Prevalence and clinical implications of hypocalcemia in acutely ill patients in a medical intensive care setting. Am J Med 1988; 84:209. 

3. Zaloga GP, Chernow B. The multifactorial basis for hypocalcemia during sepsis. Studies of the parathyroid hormone-vitamin D axis. Ann Intern Med 1987; 107:36. 

4. Sperber SJ, Blevins DD, Francis JB. Hypercalcitoninemia, hypocalcemia, and toxic shock syndrome. Rev Infect Dis 1990; 12:736.

PPI and HIV meds

 Q: 64 years old male on HIV therapy is admitted to ICU after a motor vehicle accident. General ICU orders are executed including Proton-Pump Inhibitors (PPIs) for GI prophylaxis. PPIs? (select one)

A) potentiates protease inhibitors action

B) compromises protease inhibitors action

Answer: B

There are three categories where PPIs should be used with caution: 

• Clopidogrel - PPIs compromises it's action 
• HIV protease inhibitors - PPIs compromise their action 
• Methotrexate - PPIs potentiates its action 

PPIs compromise the action of protease inhibitors by decreasing their absorption particularly rilpivirine and atazanavir.

#pharmacology

References:

1. FDA's MedWatch Safety Alerts: November 2009. Plavix and Prilosec Drug Interaction. Available at: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm192103.htm#PlavixandPrilosecDrugInteraction (Accessed on January 26, 2009). 

2. Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014 Apr;37(4):201-11. doi: 10.1007/s40264-014-0144-0. PMID: 24550106; PMCID: PMC3975086. 

3. Béïque L, Giguère P, la Porte C, Angel J. Interactions between protease inhibitors and acid-reducing agents: a systematic review. HIV Med. 2007 Sep;8(6):335-45. doi: 10.1111/j.1468-1293.2007.00482.x. PMID: 17661841. 

4. Suzuki K, Doki K, Homma M, Tamaki H, Hori S, Ohtani H, Sawada Y, Kohda Y. Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009 Jan;67(1):44-9. doi: 10.1111/j.1365-2125.2008.03303.x. Epub 2008 Nov 17. PMID: 19076159; PMCID: PMC2668083.

ANI

 Q: How alcoholic liver disease can be distinguished from nonalcoholic fatty liver disease (NAFLD)? 

 Answer: The ideal way to differentiate alcoholic liver disease from NAFLD is to determine ANI which is alcoholic liver disease to NAFLD index. The formula is 

ANI = -58.5 + 0.637 (MCV) + 3.91 (AST/ALT) – 0.406 (BMI) + 6.35 for men 

Where 

• MCV = mean corpuscular volume 
• AST/ALT = aminotransferase levels 
• BMI = body mass index (BMI) 

ANI greater than zero is probably due to alcoholic liver disease and an ANI less than zero favors NAFLD. 

In the second step, the probability of alcoholic liver disease is then calculated using the value of ANI.

 Probability = eANI/(1+eANI)

The old rule of AST to ALT ratio >2 for alcoholic liver disease still exits true for practical purposes.

#hepatology

References:

Dunn W, Angulo P, Sanderson S, et al. Utility of a new model to diagnose an alcohol basis for steatohepatitis. Gastroenterology 2006; 131:1057.

ototoxicity from aminoglycosides

 Q; Concomitant use of which pharmacological agent may help to prevent the ototoxicity of aminoglycosides?

Answer; N-acetylcysteine (NAC) 

Ototoxicity from aminoglycoside is due to oxidative stress. N-acetylcysteine (NAC) is a thiol-containing antioxidant. It is so far largely studied in End-Stage Renal Disease (ESRD) patients who are either on peritoneal dialysis (PD) or hemodialysis (HD) and received either intraperitoneal amikacin or intravenous gentamicin respectively. It has shown significantly improved outcomes. 

Despite weak evidence, it is recommended to concomitantly prescribe NAC to all patients who receive an aminoglycoside, as it is potentially a benign intervention but may benefit the patient. 

Besides NAC, aspirin has also been suggested as protective in aminoglycoside-induced ototoxicity.

#pharmacology

#ID

References:

1. Feldman L, Efrati S, Eviatar E, et al. Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N-acetylcysteine. Kidney Int 2007; 72:359. 

2. Tokgoz B, Ucar C, Kocyigit I, et al. Protective effect of N-acetylcysteine from drug-induced ototoxicity in uraemic patients with CAPD peritonitis. Nephrol Dial Transplant 2011; 26:4073. 

3. Tepel M. N-Acetylcysteine in the prevention of ototoxicity. Kidney Int 2007; 72:231. 

4. Chen Y, Huang WG, Zha DJ, et al. Aspirin attenuates gentamicin ototoxicity: from the laboratory to the clinic. Hear Res 2007; 226:178. 

5. Sha SH, Qiu JH, Schacht J. Aspirin to prevent gentamicin-induced hearing loss. N Engl J Med 2006; 354:1856.

PLEX volume

 Q: How the "Plasma volume" can be calculated in a patient?

Answer: 

The formula to estimate the plasma volume in an adult patient is: 

 Estimated plasma volume (in liters) = 0.07 x weight (kg) x (1 - hematocrit)

Clinical significance: When patient requires "plasma Exchange" (PLEX) for any reason, it is important to be aware of patient's plasma volume. It is not recommended to exchange more than 1-1.5 L of plasma in one session. This is for two reasons. First, initial 1 to 1.5 plasma volumes removes the largest concentration of the targeted substance. Second, patient may not be able to tolerate PLEX beyond this volume.

#hematology

References:

1. Kaplan AA. A simple and accurate method for prescribing plasma exchange. ASAIO Trans 1990; 36:M597. 

2. A Compendium of Transfusion Practice Guidelines, 3rd ed, Fridey JL, Marcus L (Eds), American Red Cross, 2017.

Rocuronium effect

 Q: Remifentanil ___________________ the onset of paralysis of Rocuronium. (select one)

A) expedites

B) delays

Answer: B 

Succinylcholine and Rocuronium are the two most commonly used paralytics in ICU for rapid sequence intubation (RSI). Rocuronium is a nondepolarizing neuromuscular blocking agent (NMBA). 

Rocuronium's time to intubation-level paralysis is about 45-60 seconds. Remifentanil delays this onset further by 30 to 45 seconds. On the other hand, a flush of little higher dose of Normal Saline (NS) i.e., 20 mL after Rocuronium IV push decreases the time to onset as well as prolongs its effect. Magnesium infusion prolongs the time of its paralysis. 

Rocuronium dose should be calculated with ideal body weight of the patient. The usual dose is 1 to 1.2 mg/kg IV bolus.

#procedures

#pharmacology

References:

1. Ishigaki S, Masui K, Kazama T. Saline Flush After Rocuronium Bolus Reduces Onset Time and Prolongs Duration of Effect: A Randomized Clinical Trial. Anesth Analg 2016; 122:706. 

2. April MD, Arana A, Pallin DJ, et al. Emergency Department Intubation Success With Succinylcholine Versus Rocuronium: A National Emergency Airway Registry Study. Ann Emerg Med 2018; 72:645. 

3. Na HS, Hwang JW, Park SH, et al. Drug-administration sequence of target-controlled propofol and remifentanil influences the onset of rocuronium. A double-blind, randomized trial. Acta Anaesthesiol Scand 2012; 56:558. 

4. Hans GA, Bosenge B, Bonhomme VL, et al. Intravenous magnesium re-establishes neuromuscular block after spontaneous recovery from an intubating dose of rocuronium: a randomised controlled trial. Eur J Anaesthesiol 2012; 29:95.

Bone marrow Bx in drug-induced pancytopenia

 Q: 24 years old female is admitted to ICU with severe pancytopenia after 12 weeks course of anti-acne medication. Immediate bone marrow biopsy is indicated.

A) True

B) False

Answer: B

An emergent/immediate bone marrow biopsy is usually of no help in drug induced pancytopenia. Bone marrow may only show aplasia or hypoplasia without any clue towards the cause. Offending/suspected drug needs to be discontinued followed by serial blood counts and clinical observation. 

Bone marrow biopsy in early recovery phase is also not recommended unless an hematologist find it necessary. The biggest caveat of bone marrow biopsy in drug induced pancytopenia is the high erroneous diagnosis of acute leukemia. In this phase bone marrow may show a “maturation arrest” as hematopoiesis has only progressed to an immature stage of maturation.

Hematologist should be consulted to make decision in such a tricky situation.

#hematology

#pharmacology

Reference:

Nancy Berliner: Approach to the adult with pancytopenia - UpToDate; 2021

Link: https://www.uptodate.com/contents/approach-to-the-adult-with-pancytopenia

urine centrifuge

 Q: On urine centrifuge, myoglobinuria will appear as? (select one)

A) sediment red

B) supernatant red

Answer: B

Many academic centers have small ICU labs of their own (though not a popular idea in the USA), where simple tests can be done to determine differential diagnoses. Here is one simple algorithm for patients who have red or brown urine.

#laboratory-scince

#nephrology

Reference:
 

Etiology and evaluation of hematuria in adults Authors:Mark A Perazella, MD, FACP, Michael P O'Leary, MD : Etiology and evaluation of hematuria in adults : UpToDate: 2021 

Link: https://www.uptodate.com/contents/etiology-and-evaluation-of-hematuria-in-adults 

NOTE: ALL RIGHTS OF THE ABOVE IMAGE IS RESERVED WITH UpToDate - AND SHOULD BE USE EXCLUSIVELY AND ONLY FOR EDUCATIONAL PURPOSE WITHOUT ANT COMMERCIAL INTENT.

BRASH

 Q: BRASH syndrome requires to have EKG demonstration of hyperkalemia? 

A) True

B) False

Answer: B

BRASH syndrome represents a synergistic effect in the body due to 

• Bradycardia
• Renal Failure
• AV blockade
• Shock, and 
• Hyperkalemia

It is common in elderly patients and mostly due to a combination of hyperkalemia and AV nodal blocking drugs such as beta-blockers (BB), calcium channel blockers (CCB), amiodarone, and digoxin. It is common in patients with renal insufficiency. The addition of ACE inhibitors may catalyze this synergism.

It requires a holistic way of treatment by simultaneously managing each component of the syndrome - hyperkalemia, bradycardia, and hypovolemia (renal hypoperfusion). 

These patients may easily deceive a clinician as EKG may or may not have signs of hyperkalemia i.e., peaked T waves and/or QRS prolongation.

#cardiology

#electrolytes

#nephrology

#pharmacology

References:

1. Farkas JD, Long B, Koyfman A, Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia. J Emerg Med 2020; 59:216.

2. Park DS, Fishman GI. The cardiac conduction system. Circulation 2011; 123:904.

Happy New Year