stroke due to cardiac catheterization procedure

Q: Which of the following is NOT considered a risk factor for stroke after cardiac catheterization? - select one

A) Emergency procedure

B) Longer procedure time

C) Radial artery access

D) Greater contrast use

E) Deploying intra-aortic balloon pump

Answer: C

Although relatively less acknowledged, stroke due to the cardiac catheterization procedure is relatively common. Both ischemic and hemorrhagic strokes can occur. Risk factors include:

• Older age 
• Hypertension
• Diabetes mellitus
• History of stroke
• Kidney failure
• Heart failure
• Severe coronary artery atherosclerotic disease
• Coronary artery thrombus
• Carotid artery disease
• Emergent procedure, including acute coronary syndrome
• Longer procedure time
• Greater contrast use
• Retrograde catheterization of the left ventricle in patients with aortic stenosis
• Interventions at bypass grafts
• Use of an intra-aortic balloon pump
• Use of anticoagulation or thrombolytic agents for acute myocardial infarction

Either transfemoral or transradial access has a similar risk of stroke due to the cardiac catheterization procedure.

#procedures

#cardiology

References:

1. Feng YQ, He XY, Song FE, Chen JY. Association between Contrast Media Volume and 1-Year Clinical Outcomes in Patients Undergoing Coronary Angiography. Chin Med J (Engl). 2018 Oct 20;131(20):2424-2432. doi: 10.4103/0366-6999.243563. PMID: 30334527; PMCID: PMC6202589.

2. Korn-Lubetzki I, Farkash R, Pachino RM, Almagor Y, Tzivoni D, Meerkin D. Incidence and risk factors of cerebrovascular events following cardiac catheterization. J Am Heart Assoc. 2013 Nov 14;2(6):e000413. doi: 10.1161/JAHA.113.000413. PMID: 24231658; PMCID: PMC3886771.

3. Tanaka A, Node K. Prediction of Stroke After Cardiac Catheterization: No Reason, No Stroke. J Atheroscler Thromb. 2018 Mar 1;25(3):221-223. doi: 10.5551/jat.ED086. Epub 2017 Sep 20. PMID: 28931783; PMCID: PMC5868507.

Young's Syndrome

Q: What is Young's syndrome?

Answer:

Young's syndrome is usually a triad of 

• bronchiectasis
• sinusitis, and 
• obstructive azoospermia 

WITHOUT any evidence of Cystic Fibrosis (CF). 

Previously, it was attributed to childhood exposure to mercury. Now, its etiology is linked to genetically occurring primary ciliary dyskinesia (PCD). 

#pulmonary

#genetics

References:

1. Hendry WF, A'Hern RP, Cole PJ. Was Young's syndrome caused by exposure to mercury in childhood? BMJ 1993; 307:1579.

2. Ito M, Morimoto K, Ohashi M, Wakabayashi K, Miyabayashi A, Yamada H, Hijikata M, Keicho N. Primary Ciliary Dyskinesia Due to Compound Heterozygous Variants in CFAP221 with Obstructive Azoospermia: Young's Syndrome May Be a Phenotype of Primary Ciliary Dyskinesia. Intern Med. 2025 Feb 1;64(3):423-428. doi: 10.2169/internalmedicine.3978-24. Epub 2024 Jul 4. PMID: 38960684; PMCID: PMC11867755.

Unusual complications of infectious mononucleosis

Q: Describe atypical complications associated with infectious mononucleosis (IM).

Answer: 

Although most of the patients with IM recover in a week or two with supportive care, and are left with fatigue for another few weeks, a few patients may end up having potentially acute and sub-acute fatal complications such as:

• Airway obstruction
• Splenic rupture 
• Hemophagocytic lymphohistiocytosis (HLH) 
• Fulminant liver failure
• Severe hemolytic or aplastic anemia

#ID

References:

1. Lloyd AM, Reilly BK. Infectious Mononucleosis and Upper Airway Obstruction: Intracapsular Tonsillectomy and Adenoidectomy With Microdebrider for Prompt Relief. Ear Nose Throat J. 2021 Dec;100(10_suppl):958S-960S. doi: 10.1177/0145561320930046. Epub 2020 Jun 8. PMID: 32511006.

2. Bartlett A, Williams R, Hilton M. Splenic rupture in infectious mononucleosis: A systematic review of published case reports. Injury 2016; 47:531.

3. Huang R, Wu D, Wang L, Liu P, Zhu X, Huang L, Chen M, Lv X. A predictive model for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Front Immunol. 2024 Dec 5;15:1503118. doi: 10.3389/fimmu.2024.1503118. PMID: 39703509; PMCID: PMC11655318.

4. Seog WJ, Steinberg J, Ghafary I, Clores M, Aroniadis O. Severe Acute Liver Injury From Hemophagocytic Lymphohistiocytosis Related to Disseminated Herpes Simplex Virus Type 1 in a Young Immunocompetent Man. ACG Case Rep J. 2025 Jan 4;12(1):e01581. doi: 10.14309/crj.0000000000001581. PMID: 39764152; PMCID: PMC11703433.

Preferred rectal benzo in convulsive status epilepticus

Q: Which of the following medicines is preferred as per rectal administration in convulsive status epilepticus? - select one

A) Lorazepam 

B) Midazolam 

C) Diazepam 

D) Chlordiazepoxide

E) Flurazepam

Answer: C

The objective of treatment in convulsive status epilepticus is to administer the first line of drug, i.e., benzodiazepines, as soon as possible (ASAP!)

IF an Intravenous line cannot be established quickly, other routes should be considered. As a rule of thumb,

• Lorazepam (choice A) is preferred for the intravenous (IV) route
• Midazolam (choice B) is preferred for intramuscular (IM), intranasal, or buccal route, and
• Diazepam (choice C) is preferred for rectal administration

It is prudent to order other intravenous nonbenzodiazepine antiseizures such as levetiracetam, fosphenytoin, valproate, lacosamide, or phenobarbital simultaneously as per the clinical judgement of the physician.

Chlordiazepoxide (choice D) is preferred to prevent the recurrence of seizures.

Flurazepam (choice E), one of the earliest 'benzos' and less used now, is good as an anti-anxiety or as a sleep medicine.

#Neurology

References:

1. Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr 2016; 16:48.

2. Prasad M, Krishnan PR, Sequeira R, Al-Roomi K. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev 2014; :CD003723.

3. Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med 2012; 366:591.

4. Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001; 345:631.

5. Kellinghaus C, Rossetti AO, Trinka E, et al. Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE). Ann Neurol 2019; 85:421.

EGPA and steroids

Q: What is the caveat in interpreting peripheral blood eosinophilia in patients with suspected Eosinophilic granulomatosis with polyangiitis (EGPA or Churg-Strauss syndrome)?

Answer: Glucocorticoids

EGPA is a vasculitis of the small and medium-sized arteries, described 75 years ago by Churg and Strauss. Common symptoms are asthma, nasal and sinus symptoms, and peripheral neuropathy. It can involve many body organs and progress slowly, and it is usually diagnosed in the fifth decade of life. As it gets worse, the patient develops pulmonary opacities, cardiomyopathy, renal insufficiency, and gastrointestinal (GI) symptoms. 

Peripheral blood eosinophilia is the most characteristic finding with absolute blood eosinophil counts ≥1000 cells/microL (or greater than 10 percent of the total leukocyte count). This blood workup finding should raise suspicion for EGPA. 

Many patients have been administered glucocorticoids to control their chronic symptoms from EGPA. Glucocorticoids may reduce or fluctuate eosinophil counts and falsely rule out EGPA. 

#rheumatology

References:

1. CHURG J, STRAUSS L. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol 1951; 27:277.

2. Cottin V, Bel E, Bottero P, et al. Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Autoimmun Rev 2017; 16:1.

3. Grayson PC, Ponte C, Suppiah R, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis 2022; 81:309.

Flumazenil use in non-benzodiazepine overdose

Q: Flumazenil can be an effective antidote for which other drugs besides benzodiazepines?

Answer: Flumazenil is traditionally used as an antidote in patients with benzodiazepine overdose, but it is effective in overdoses of non-benzodiazepine sleep enhancers, namely zolpidem (Ambien) and zaleplon (Sonata) -popularly known as "Z" drugs.

Flumazenil reverses the effects of benzodiazepines by competitive inhibition at the benzodiazepine binding site on the GABA-a receptor.

Additionally, it has been used in the treatment of hepatic encephalopathy.

#toxicity

#pharmacology

References:

1. Patat A, Naef MM, van Gessel E, Forster A, Dubruc C, Rosenzweig P. Flumazenil antagonizes the central effects of zolpidem, an imidazopyridine hypnotic. Clin Pharmacol Ther. 1994 Oct;56(4):430-6. doi: 10.1038/clpt.1994.157. PMID: 7955804.

2. An H, Godwin J. Flumazenil in benzodiazepine overdose. CMAJ. 2016 Dec 6;188(17-18):E537. doi: 10.1503/cmaj.160357. Epub 2016 Nov 14. PMID: 27920113; PMCID: PMC5135539.

Stool osmolality

Q: By default, stool osmolality is equal to plasma osmolality.

A) True

B) False

Answer: A

Normal fecal fluid's osmolality is about equal to the plasma osmolality of 290 mOsm/kg. The colon cannot dilute stool to an osmolality lower than that of plasma. 

This simple piece of information has immense clinical implications. 

If stool osmolality is less than 250 mOsm/kg, it suggests factitious diarrhea or the addition of water or a hypotonic solution. Frequently, urine is used for this purpose, which is easy to do, but urine is a hypotonic solution.

It is worth noting that stool osmolality also increases due to the breakdown of carbohydrates by bacteria into smaller, osmotically active molecules.

#GI

#electrolytes

References:

1. Thomas PD, Forbes A, Green J, et al. Guidelines for the investigation of chronic diarrhoea, 2nd edition. Gut 2003; 52 Suppl 5:v1.

2. Topazian M, Binder HJ. Brief report: factitious diarrhea detected by measurement of stool osmolality. N Engl J Med 1994; 330:1418.

3. Pollock RC, Banks MR, Fairclough PD, Farthing MJ. Dilutional diarrhea: underdiagnosed and over-investigated. Eur J Gastroenterol Hepatol 2006; 12:609.

Bicarb in severe LA

Q: All of the following are potential effects of bicarbonate therapy in lactic acidosis EXCEPT? - select one

A) increase partial pressure of carbon dioxide (pCO2)

B) decrease production of lactate

C) decreased ionized calcium

D) expansion of the extracellular space

E) increased serum sodium concentration

Answer: B

The use of bicarbonate therapy in patients with lactic acidosis remained controversial, but most clinicians agree that the benefit may offset risks when pH goes lower than 7.1. Between pH 7.1 and 7.2, it should be used judiciously. There is some weak evidence that bicarbonate therapy may potentially prevent the need for dialysis and improve survival (reference #1).

Exogenous bicarbonate in lactic acidosis aims to 'buy time' so the underlying disease process can be reversed.

All of the choices in the above questions are correct EXCEPT choice B. Rapid infusions of sodium bicarbonate may accelerate lactate production.

#acid-base

References:

1. Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet 2018; 392:31.

2. Ahn S, Kim YJ, Sohn CH, Seo DW, Lim KS, Donnino MW, Kim WY. Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study. J Thorac Dis. 2018 Apr;10(4):2295-2302. doi: 10.21037/jtd.2018.03.124. PMID: 29850134; PMCID: PMC5949471.

3. Lo KB, Garvia V, Stempel JM, Ram P, Rangaswami J. Bicarbonate use and mortality outcome among critically ill patients with metabolic acidosis: A meta analysis. Heart Lung. 2020 Mar-Apr;49(2):167-174. doi: 10.1016/j.hrtlng.2019.10.007. Epub 2019 Nov 14. PMID: 31733880.

unconventional uses of Haloperidol

Q: Give some unconventional uses of Haloperidol?

Answer: Although Haldol has slowly lost its charm in the ICU over the years due to the availability of safer, centrally acting drugs, it has some immense good properties that make it useful in other non-delirium conditions in the ICU.

• Adjunctive treatment of alcohol and opioid withdrawal
• Treatment of disorders such as tics, Tourette syndrome, and chorea
• Treatment of severe nausea/emesis (postoperative, chemotherapy, etc.)
• Adjunctive treatment of severe chronic pain (with analgesics)
• Also used in the treatment of intractable hiccups

#pharmacology

#toxicity

#GI

#pain

References:

1. Ghaderi-Bafti F, Zarghami M, Ahmadi A, Moosazadeh M, Hadinezhad P, Hendouei N. Effectiveness and Safety of Haloperidol Add-on Methadone in Acute Opium Withdrawal Symptoms of Opioid-dependent Patients: A Double-blind Randomized Placebo-controlled Clinical Trial. Addict Health. 2021 Apr;13(2):85-94. doi: 10.22122/ahj.v13i2.287. PMID: 34703529; PMCID: PMC8519612.

2. Spies CD, Otter HE, Hüske B, Sinha P, Neumann T, Rettig J, Lenzenhuber E, Kox WJ, Sellers EM. Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU. Intensive Care Med. 2003 Dec;29(12):2230-2238. doi: 10.1007/s00134-003-2033-3. Epub 2003 Oct 14. PMID: 14557857.

3. Eddy CM, Rickards HE, Cavanna AE. Treatment strategies for tics in Tourette syndrome. Ther Adv Neurol Disord. 2011 Jan;4(1):25-45. doi: 10.1177/1756285610390261. PMID: 21339906; PMCID: PMC3036957.

4. Shahsavari D, Reznick-Lipina K, Malik Z, Weiner M, Jehangir A, Repanshek ZD, Parkman HP. Haloperidol Use in the Emergency Department for Gastrointestinal Symptoms: Nausea, Vomiting, and Abdominal Pain. Clin Transl Gastroenterol. 2021 Jun 1;12(6):e00362. doi: 10.14309/ctg.0000000000000362. PMID: 34060494; PMCID: PMC8162512.

5. Cowling M, Covington S, Roehmer C, Musey P. Characterizing the role of haloperidol for analgesia in the Emergency Department. J Pain Manag. 2019;12(2):141-146. PMID: 33193995; PMCID: PMC7665221.

6. Woelk CJ. Managing hiccups. Can Fam Physician. 2011 Jun;57(6):672-5, e198-201. Erratum in: Can Fam Physician. 2021 Feb;67(2):84. doi: 10.46747/cfp.670284. PMID: 21673211; PMCID: PMC3114667.

electric shock radiating down with flexion of the neck

Q: 32 years old female with a known history of Multiple Sclerosis (MS) presented with complaints of an electric shock radiating down as she flexes her neck. Your diagnosis?

Answer: Lhermitte sign 

The Lhermitte sign is a known symptom of MS. It is a transient sensory symptom characterized by an electric shock that radiates down the spine or into the limbs, mostly after flexion of the neck. It occurs in about 15-20% of MS patients.

If it occurs in a non-MS patient, other diagnoses should be considered, such as tumors, cervical disc herniation, post-radiation myelopathy, and trauma.

The exact etiology is unknown, but demyelination and hyperexcitability appear to be the cause.

#neurology

References:

1. Kanchandani R, Howe JG. Lhermitte's sign in multiple sclerosis: a clinical survey and review of the literature. J Neurol Neurosurg Psychiatry 1982; 45:308.

2. García-Moreno JM, Izquierdo G. Signo de Lhermitte [Lhermitte's sign]. Neurologia. 2002 Mar;17(3):143-50. Spanish. PMID: 11927103.

3. Khare S, Seth D. Lhermitte's Sign: The Current Status. Ann Indian Acad Neurol. 2015 Apr-Jun;18(2):154-6. doi: 10.4103/0972-2327.150622. PMID: 26019410; PMCID: PMC4445188.

IM

Q: Why is Infectious mononucleosis (IM) called Infectious mononucleosis (IM)?

Answer: 

This question aims to teach the habit of understanding nomenclatures in medicine and science. The pathophysiology can be understood well if the nomenclature is understood well.

Infectious mononucleosis (IM) is characterized by absolute lymphocytosis and atypical mononuclear cells in the blood. In fact, the name of the disease was changed 30 years after its discovery from "Drüsenfieber" (glandular fever) to "infectious mononucleosis."

Infectious mononucleosis (IM) is marked by a triad of 

• fever
• tonsillar pharyngitis, and 
• lymphadenopathy  

The underlying cause is Epstein-Barr virus (EBV).

#ID

References:

1. Sprunt TP, Evans FA. Mononucleosis leukocytosis in reaction to acute infections (infectious mononucleosis). Bull Johns Hopkins Hosp 1920; 31:409.

2. Evans AS. The history of infectious mononucleosis. Am J Med Sci 1974; 267:189.

3. Dunmire SK, Hogquist KA, Balfour HH. Infectious Mononucleosis. Curr Top Microbiol Immunol 2015; 390:211.

Ganciclovir and Valganciclovir

Q: What is the difference between Ganciclovir and Valganciclovir?

Answer: 

Ganciclovir and Valganciclovir are the mainstay of cytomegalovirus (CMV) viremia treatments.

Valganciclovir, an L-valyl ester of ganciclovir. Its most significant advantage is that it can be given orally with an excellent bioavailability. It is well absorbed and rapidly hydrolyzed to ganciclovir hepatically and in the intestinal wall. The best equivalent can be described as: The systemic exposure of a 900 mg dose of valganciclovir in adults is similar to a single dose of 5 mg/kg of IV ganciclovir, with absolute bioavailability of about 60 percent. It is usually given with food.

Ganciclovir given as an IV has an intracellular half-life of 16.5 hours as ganciclovir triphosphate. Clearance is directly correlated to glomerular filtration rate (GFR). Ganciclovir's oral form has poor bioavailability and has been replaced by Valganciclovir.

Hemodialysis (HD) decreases serum concentration of ganciclovir and valganciclovir by about 50 percent.

#pharmacology

#ID

References:

1. Markham A, Faulds D. Ganciclovir. An update of its therapeutic use in cytomegalovirus infection. Drugs 1994; 48:455.

2. Cvetković RS, Wellington K. Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. Drugs 2005; 65:859.

3. Curran M, Noble S. Valganciclovir. Drugs 2001; 61:1145.

K-Phos

Q: 21 years old female with Anorexia Nervosa is admitted to the ICU with severe electrolyte imbalance. The patient has been prescribed "K-Phos-Rider". What is the usual ratio of Phosphate: Potassium in combo intravenous (IV) administration?

Answer: 1:1.46 

If both are deficient, potassium and phosphate are usually administered in a combo IV infusion.

1 mmol of intravenous phosphate delivers 1.46 meq of potassium in "K-phos rider". 

Usually, 7.5 mmol of phosphate with 10 meq of potassium is administered. It should be infused over a period of an hour.

#electrolytes

References/further reading:

1. Perreault MM, Ostrop NJ, Tierney MG. Efficacy and safety of intravenous phosphate replacement in critically ill patients. Ann Pharmacother. 1997 Jun;31(6):683-8. doi: 10.1177/106002809703100603. PMID: 9184705.

2. Hemstreet BA, Stolpman N, Badesch DB, May SK, McCollum M. Potassium and phosphorus repletion in hospitalized patients: implications for clinical practice and the potential use of healthcare information technology to improve prescribing and patient safety. Curr Med Res Opin. 2006 Dec;22(12):2449-55. doi: 10.1185/030079906X148463. PMID: 17257459.

3. Charron T, Bernard F, Skrobik Y, Simoneau N, Gagnon N, Leblanc M. Intravenous phosphate in the intensive care unit: more aggressive repletion regimens for moderate and severe hypophosphatemia. Intensive Care Med. 2003 Aug;29(8):1273-8. doi: 10.1007/s00134-003-1872-2. Epub 2003 Jul 5. PMID: 12845429.

goiter and choking

Q: 53 years old female presented with progressively worsening choking sensation over months. On exam, noticed to have stridor. CT chest and neck confirmed the diagnosis of substernal goiter. At this point, the probability of having symptomatic obstruction is less than? - select one

A) 8 mm

B) 15 mm

Answer: A

This question aims to highlight that once cervical or substernal thyroid goiter becomes symptomatic, the margin of safety drastically narrows. The patient largely remains asymptomatic or may report mild symptoms until the tracheal diameter becomes less than 8 mm. Moreover, as the tracheal luminal diameter becomes less than 5 mm, the chances of a high-grade complication become high, with stridor or wheezing at rest.

Other major complications of such goiter include the development of severe acute pain, which may signify hemorrhage into a nodule. 

Fortunately, these goiters are very slow to expand, and most patients, more females, are in their fifth or sixth decades of life.

Exertional and/or positional dyspnea occurs whenever the thyroid moves into the thoracic inlet. This mostly occurs in bending.

Other symptoms are progressive cough, choking sensation, dysphagia, compression of the recurrent laryngeal nerve causing vocal cord palsy and hoarseness, phrenic nerve paralysis, Horner's syndrome, and, in severe cases, jugular vein compression and/or thrombosis, cerebrovascular steal syndromes, and/or superior vena cava syndrome.

#surgical-critical-care

#ENT

References:

1. Al-Bazzaz F, Grillo H, Kazemi H. Response to exercise in upper airway obstruction. Am Rev Respir Dis 1975; 111:631.

2. Shaha AR, Burnett C, Alfonso A, Jaffe BM. Goiters and airway problems. Am J Surg 1989; 158:378.

3. Torres A, Arroyo J, Kastanos N, et al. Acute respiratory failure and tracheal obstruction in patients with intrathoracic goiter. Crit Care Med 1983; 11:265.

4. Banks CA, Ayers CM, Hornig JD, et al. Thyroid disease and compressive symptoms. Laryngoscope 2012; 122:13.

Vision loss in pHTN patient

Q: 44 years old female with underlying pulmonary hypertension (pHTN), recently discharged from the hospital, presented back to the ED with vision loss in one eye. Emergent ophthalmic consult is obtained. The patient is found to have serious retinal detachment (SRD). Which drug could be a culprit?

Answer: Phosphodiesterase 5 Inhibitors (PDE5) inhibitor 

Minor vision issues with PDE5 inhibitors are well known, such as blue vision (cyanopsia) with sildenafil, which occurs due to a cross-reaction with the PDE6 inhibitor in the retina. Interestingly, cyanopsia has not been reported with vardenafil, tadalafil, or avanafil.

Major serious eye effects are not common but can be devastating, such as nonarteritic anterior ischemic optic neuropathy (NAION), serious retinal detachment (SRD), and retinal vein occlusion (RVO), particularly in patients who are already at high risk, such as older age, HTN, dyslipidemia, and diabetes. 

# ophthalmology

#pulmonary

References:

1. Etminan M, Sodhi M, Mikelberg FS, Maberley D. Risk of Ocular Adverse Events Associated With Use of Phosphodiesterase 5 Inhibitors in Men in the US. JAMA Ophthalmol 2022; 140:480.

2. Barroso F, Ribeiro JC, Miranda EP. Phosphodiesterase Type 5 Inhibitors and Visual Side Effects: A Narrative Review. J Ophthalmic Vis Res. 2021 Apr 29;16(2):248-259. doi: 10.18502/jovr.v16i2.9088. PMID: 34055262; PMCID: PMC8126729.

3. Moschos MM, Nitoda E. Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction. Drug Des Devel Ther. 2016 Oct 19;8:3407-3413. doi: 10.2147/DDDT.S118015. PMID: 27799745; PMCID: PMC5076796.

Yellow fever- Rx

Q: What is the mainstay of treatment for yellow fever? - select one

A) IgG monoclonal antibody

B) Ribavirin 

C) Sofosbuvir 

D) Plasma exchange

E) Supportive care  

Answer: E

Unfortunately, most treatment options for yellow fever are either in the experimental stage or are ineffective.

Yellow fever can have a very dreaded course with septic shock, Metabolic acidosis, and Multi-system organ failure. The mainstay of treatment is supportive.

Ribavirin is active against the yellow fever virus but requires very high concentrations, which are extremely hard to achieve clinically. Sofosbuvir is still considered experimental.

Plasma exchange can be tried, but the evidence is very weak.

TY014 (an engineered anti-yellow fever virus human immunoglobulin (Ig)G monoclonal antibody) is also experimental. Similarly, hyperimmune globulin or monoclonal antibody carries very weak evidence of success.

#ID

#Shock

References/further readings:

1. Ho YL, Joelsons D, Leite GFC, et al. Severe yellow fever in Brazil: clinical characteristics and management. J Travel Med 2019; 26.

2. Sbrana E, Xiao SY, Guzman H, et al. Efficacy of post-exposure treatment of yellow fever with ribavirin in a hamster model of the disease. Am J Trop Med Hyg 2004; 71:306.

3. Rezende IM, Mendonça DC, Costa TA, et al. Sofosbuvir Off-label Treatment of Yellow Fever Patients During an Outbreak in Brazil, 2018: A Cohort Study. Open Forum Infect Dis 2024; 11:ofae312.

4. Ho YL, Nukui Y, Villaça PR, et al. Intensive Therapeutic Plasma Exchange-New Approach to Treat and Rescue Patients with Severe Form of Yellow Fever. Trop Med Infect Dis 2025; 10.

5. Low JG, Ng JHJ, Ong EZ, et al. Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody. N Engl J Med 2020; 383:452.

Electrolytes in GBS

Q: Which electrolyte disturbance is more common in patients with Guillain-Barré syndrome (GBS) who develop dysautonomia?

A) Hypernatremia

B) Hyponatremia

Answer: B

Dysautonomia is a dreaded side effect in GBS, which may occur in a large population of these patients. These patients are usually sicker, requiring hospitalization, more cardiogenic events, a higher disability, and mortality, including sudden death.

Hyponatremia is very common and may be a direct effect or attributed to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which occurs due to autonomic involvement.

The other usual symptoms are ileus, hyper- and/or hypotension, fever, tachycardia and/or bradycardia, and urinary retention.

#neurology

#electrolytes

References:

1. Chakraborty T, Kramer CL, Wijdicks EFM, Rabinstein AA. Dysautonomia in Guillain-Barré Syndrome: Prevalence, Clinical Spectrum, and Outcomes. Neurocrit Care 2020; 32:113.

2. Anandan C, Khuder SA, Koffman BM. Prevalence of autonomic dysfunction in hospitalized patients with Guillain-Barré syndrome. Muscle Nerve 2017; 56:331.

3. Saifudheen K, Jose J, Gafoor VA, Musthafa M. Guillain-Barre syndrome and SIADH. Neurology 2011; 76:701.

IV Vitamin K and Warfarin

Q: One dose of intravenous (IV) Vitamin K antagonizes the effects of warfarin for how many days?

Answer: About one week

A high dose of Vitamin K (= 10 mg) produces rapid reversal; however, overcorrection and warfarin resistance complicate therapy. A 10-mg dose of vitamin K antagonizes warfarin's effects on clotting factor synthesis for 7 days. Low doses (0.5-2.5 mg) reverse anticoagulation within 24 hours (taking a little longer) with less risk of overcorrection or resistance to reinstitution of therapy.

Most guidelines for warfarin reversal recommend stringent use in this regard.

#hematology

References:

1. Rivosecchi RM, Garavaglia J, Kane-Gill SL. An evaluation of intravenous vitamin k for warfarin reversal: are guideline recommendations being followed? Hosp Pharm. 2015 Jan;50(1):18-24. doi: 10.1310/hpj5001-18. PMID: 25684796; PMCID: PMC4321424.

2. Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e152S-e184S. doi: 10.1378/chest.11-2295. PMID: 22315259; PMCID: PMC3278055.

3. Polito NB, Kanouse E, Jones CMC, McCann M, Refaai MA, Acquisto NM. Effect of vitamin K administration on rate of warfarin reversal. Transfusion. 2019 Apr;59(4):1202-1208. doi: 10.1111/trf.15146. Epub 2019 Feb 4. PMID: 30714620.

Sildenafil with inhaled NO

Q: What is the advantage of adding Sildenafil with inhaled NO (iNO) in the treatment of pulmonary hypertension?

Answer: Sildenafil not only decreases the pulmonary pressures but also prevents rebound pulmonary vasoconstriction on withdrawal of inhaled NO.

#pulmonary

#pharmacology

References:

1. Namachivayam P, Theilen U, Butt WW, Cooper SM, Penny DJ, Shekerdemian LS. Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med. 2006 Nov 1;174(9):1042-7. doi: 10.1164/rccm.200605-694OC. Epub 2006 Aug 17. PMID: 16917115.

2. Raja SG. Treatment of rebound pulmonary hypertension: why not sildenafil? Anesthesiology. 2004 Dec;101(6):1480; author reply 1481. doi: 10.1097/00000542-200412000-00039. PMID: 15564966.

3. Mehta S. Sildenafil for pulmonary arterial hypertension: exciting, but protection required. Chest. 2003 Apr; 123(4): 989-92

Balint syndrome

Q: What is Balint syndrome?

Answer: Balint syndrome, initially described as psychic paralysis of visual fixation (a misnomer) 70 years ago, is a triad of 

• simultanagnosia 
• optic ataxia
• ocular apraxia 

Simultanagnosia means the inability to integrate a visual scene despite adequate acuity to resolve individual elements.

Optic ataxia is the inability to reach accurately under visual guidance. It is caused by a visual-motor coordination issue. 

Ocular apraxia is the inability to direct gaze accurately to a new target, frequently leading to difficulty reading. This is due to problems with voluntary eye movements, including difficulty shifting gaze to different objects or maintaining fixation.

Balint syndrome is often associated with neurological diseases in the parietal and occipital lobes. It signifies bilateral lesions, such as in watershed infarction or reversible cerebral vasoconstriction syndrome (RCVS). It can also be idiopathic.

#neurology

References:

1. Walsh RD, Floyd JP, Eidelman BH, Barrett KM. Bálint syndrome and visual allochiria in a patient with reversible cerebral vasoconstriction syndrome. J Neuroophthalmol 2012; 32:302.

2. Pisella L, Vialatte A, Khan AZ, Rossetti Y. Bálint syndrome. Handb Clin Neurol. 2021;178:233-255. doi: 10.1016/B978-0-12-821377-3.00011-8. PMID: 33832679.

3. HECAEN H, DE AJURIAGUERRA J. Balint's syndrome (psychic paralysis of visual fixation) and its minor forms. Brain. 1954;77(3):373-400. doi: 10.1093/brain/77.3.373. PMID: 13208876.

4. Ghoneim A, Pollard C, Greene J, Jampana R. Balint syndrome (chronic visual-spatial disorder) presenting without known cause. Radiol Case Rep. 2018 Sep 20;13(6):1242-1245. doi: 10.1016/j.radcr.2018.08.026. PMID: 30258515; PMCID: PMC6148828.

PE in schizophrenia

Q: 59 years female with schizophrenia presented to ED with Shortness of Breath (SOB). Wife reports that recently patient was having a bout of depression and spent all days lying on sofa watching TV. On EKG, the patient was found to have an increased QTc interval. Also, CT-Angiogram of the chest showed pulmonary Embolism (PE). What drug is the most probable culprit?

Answer: Clozapine

Clozapine is considered one of the mainstay drug treatments for schizophrenia. Unfortunately, it has an increased risk of venous thromboembolism. Moreover, mortality from clotting complications in these patients is very high, with almost half having a fatal outcome (44%). Risk factors include:

• Genetic factors (like factor V Leiden mutation or high concentration of factor VIII)
• Recent immobilization
• Recent surgery
• Pregnancy or the postpartum state
• Obesity

Although evidence is weak, aspirin and statins have been suggested in patients on Clozapine to reduce the risk of venous thromboembolism. Patients should also be advised to stay active and mobile while on Clozapine.

In the above question, increased QTc prolongation is given as a hint.

#pharmacology

#psychiatry

References:

1. Kortepeter C, Chen M, Knudsen JF, et al. Clozapine and venous thromboembolism. Am J Psychiatry 2002; 159:876.

2. Farah RE, Makhoul NM, Farah RE, Shai MD. Fatal venous thromboembolism associated with antipsychotic therapy. Ann Pharmacother 2004; 38:1435.

3. Paciullo CA. Evaluating the association between clozapine and venous thromboembolism. Am J Health Syst Pharm 2008; 65:1825.

Abdominal exam in ACS

Q: 44 years old male is admitted to the ICU with severe acute pancreatitis after a bout of binge drinking at a Saturday night party. Patient required massive fluid resuscitation. 24 hours after admission, patient complains of worsening abdominal pain. Nurse raised the concern for acute abdominal compartment syndrome (ACS). A good abdominal exam is a better indicator of developing acute ACS than other parameters.

A) True

B) False

Answer: B

This question has two objectives. First, in acute pancreatitis or in any other critical situation where a patient requires a large amount of intravenous resuscitation, the development of ACS is always an unintended consequence. Second, unfortunately, physical examination of the abdomen remained a poor predictor of ACS. Measurement of bladder pressure is the gold standard. 

Other clinical signs should also be considered, such as worsening oliguria, increased ventilatory requirement if intubated, worsening pulmonary insufficiency otherwise, hypotension, tachycardia, an elevated jugular venous pressure (JVP), jugular venous distension, peripheral edema, abdominal tenderness, evidence of hypoperfusion (cool skin), and mental status change. Rising lactic acidosis is usually a norm.

#GI

#surgical-critical-care

References:

1. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. I. Definitions. Intensive Care Med 2006; 32:1722.

2. Kirkpatrick AW, Brenneman FD, McLean RF, et al. Is clinical examination an accurate indicator of raised intra-abdominal pressure in critically injured patients? Can J Surg 2000; 43:207.

3. Sugrue M, Bauman A, Jones F, et al. Clinical examination is an inaccurate predictor of intraabdominal pressure. World J Surg 2002; 26:1428.

Cefiderocol

Q: Cefiderocol belongs to which generation of cephalosporins? - select one

A) First generation 

B) Second generation 

C) Third generation

D) Fourth generation 

E) Fifth generation 

F) None of the above

Answer: F

Cefiderocol is unique because it does not belong to any of the generations of cephalosporins. It is a novel siderophore cephalosporin. It is active against multidrug-resistant (MDR) gram-negative bacteria, including ESBL- or carbapenemase-producing organisms and (MDR) P. aeruginosa, A. baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. 

#pharmacology

References:

1. Parsels KA, Mastro KA, Steele JM, Thomas SJ, Kufel WD. Cefiderocol: a novel siderophore cephalosporin for multidrug-resistant Gram-negative bacterial infections. J Antimicrob Chemother. 2021 May 12;76(6):1379-1391. doi: 10.1093/jac/dkab015. PMID: 33532823.

2. Wu JY, Srinivas P, Pogue JM. Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms. Infect Dis Ther. 2020 Mar;9(1):17-40. doi: 10.1007/s40121-020-00286-6. Epub 2020 Feb 18. PMID: 32072491; PMCID: PMC7054475.

Basis of rouleaux formation

Q: What's the basis of Rouleaux formation in diseases with increased levels of plasma proteins?

Answer: When red blood cells (RBCs) stack together, like a stack of coins, it's called a Rouleaux formation.

Rouleaux formation is reported in many diseases with increased plasma protein levels, such as multiple myeloma, Waldenström's macroglobulinemia, inflammatory disorders, and high fibrinogen and immunoglobulin levels. These proteins neutralize the normally repulsive negative charges on the RBC membranes, causing them to adhere like a stack of coins.

#hematology

#physiology

References:

1. Abramson N. Rouleaux formation. Blood. 2006 Jun 1;107(11):4205. PMID: 16739263.

2. Skalak R, Zarda PR, Jan KM, Chien S. Mechanics of Rouleau formation. Biophys J. 1981 Sep;35(3):771-81. doi: 10.1016/S0006-3495(81)84826-6. PMID: 7272459; PMCID: PMC1327562.

3. Chien S, Jan K. Ultrastructural basis of the mechanism of rouleaux formation. Microvasc Res. 1973 Mar;5(2):155-66. doi: 10.1016/0026-2862(73)90068-x. PMID: 4694282.

Picture source: Baker, W. Morrant, Harris, Vincent Dormer Kirkes, William Senhouse - Hand-book of physiology. 13th ed., Year: 1892 (1890s), Publisher: London : John Murray. Contributing Library: Francis A. Countway Library of Medicine

MALA and bicarb

Q: 56 years old male is admitted to the ICU with an intentional overdose of Metformin. Patient is in severe refractory shock, lactic acidosis, and pH of 6.9. Preparation of dialysis started. In between, a decision was made to administer sodium bicarbonate. What should be the target PH in this case of Metformin Associated Lactic Acidosis (MALA)?

Answer: 7.1

The objective of this question is to highlight the dangers of excessive sodium bicarbonate use, especially in MALA. The recommended target arterial pH is just above 7.1 or above 7.3 in patients with severe acute kidney injury. This level of pH can be maintained until the acute toxicity resolves. The use of sodium bicarbonate in MALA is controversial, and clinicians are advised to take a bare minimum approach.

Sodium bicarbonate may induce 

• Hemoglobin dissociation curve to the left
• Sodium load
• Rebound metabolic alkalosis
• Serum potassium and calcium disturbances
• Decreased myocardial contractility
• Increased CO2 production
• Reflex vasodilation after bolus injection 

#toxicity

References:

1. Heaney D, Majid A, Junor B. Bicarbonate haemodialysis as a treatment of metformin overdose. Nephrol Dial Transplant 1997; 12:1046.

2. Teale KF, Devine A, Stewart H, Harper NJ. The management of metformin overdose. Anaesthesia 1998; 53:698.

compensatory changes to maintain oxygen delivery in acute anemia

Q: In an isovolemic healthy person, acute reduction in the hemoglobin (Hb) concentration induces all of the following compensatory changes to maintain oxygen delivery EXCEPT? - select one

A) Increase in heart rate from basal level

B) Increase stroke volume

C) Increase cardiac index 

D) Decrease tissue oxygen extraction

Answer: D

In a healthy isovolumic person, a reduction in the Hb concentration induces many compensatory changes to maintain the net oxygen delivery. All of the above choices are true EXCEPT choice D. With an increase in heart rate, stroke volume, and cardiac Index (remember high cardiac output failure in anemia!), there is an increase in tissue oxygen extraction.

The most important underlying factor in such compensatory mechanisms is to stay isovolemic. That's why there is a famous saying in Critical Care Medicine: "Blood does not save lives; blood volume saves lives."

Some experts even suggest that a healthy individual with such compensatory mechanisms can maintain oxygen delivery up to Hb/Hematocrit (Hct) concentration as low as 5 g/dL / Hct 15 %, given intravascular volume is maintained.

#hematology

#hemodynamics

References:

1. Weiskopf RB, Viele MK, Feiner J, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998; 279:217.

2. Bliss S. Anemia and Oxygen Delivery. Vet Clin North Am Small Anim Pract. 2015 Sep;45(5):917-30. doi: 10.1016/j.cvsm.2015.04.006. Epub 2015 May 29. PMID: 26033442.

3. Bunn HF. Oxygen Delivery in the Treatment of Anemia. N Engl J Med. 2022 Dec 22;387(25):2362-2365. doi: 10.1056/NEJMra2212266. PMID: 36546628.

Common drug interaction in cardiac patients

Case: 58 years old male is admitted to the ICU with Atrial fibrillation with RVR (rapid ventricular rate). The patient did well with rate control therapy and has been discharged from the hospital on metoprolol, aspirin, lisinopril, simvastatin, and Amiodarone. The patient presented back after 2 weeks to the ED with complaints of severe generalized weakness. The patient was found to be in acute renal failure. Besides hyperkalemia and elevated creatinine, the patient was found to have CPK in the 60,000 range. Troponin is normal. Which two drug interactions may be a culprit?

Answer: Simvastatin with amiodarone.

Simvastatin with amiodarone interaction may cause rhabdomyolysis and lead to acute renal failure. The FDA has already put out a warning regarding this drug interaction. This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone.

The precise mechanism is not clearly known, but amiodarone inhibits the cytochrome P450 3A4 (CYP3A4) enzyme, which is also the enzyme that metabolizes simvastatin.

Using other statins without relevant CYP metabolism (e.g., pravastatin) should be okay.

#pharmacology

#cardiology

Reference: 

1. Marot A, Morelle J, Chouinard VA, Jadoul M, Lambert M, Demoulin N. Concomitant use of simvastatin and amiodarone resulting in severe rhabdomyolysis: a case report and review of the literature. Acta Clin Belg. 2011 Mar-Apr;66(2):134-6. doi: 10.2143/ACB.66.2.20625533. PMID: 21630612.

2. Roten L, Schoenenberger RA, Krähenbühl S, Schlienger RG. Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother. 2004 Jun;38(6):978-81. doi: 10.1345/aph.1D498. Epub 2004 Apr 6. PMID: 15069169.

3. Becquemont L, Neuvonen M, Verstuyft C, Jaillon P, Letierce A, Neuvonen PJ, Funck-Brentano C. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clin Pharmacol Ther. 2007 May;81(5):679-84. doi: 10.1038/sj.clpt.6100098. Epub 2007 Feb 14. PMID: 17301736.

ALDEN

Q: ALDEN is an algorithm to determine the causality of which disease?

Answer: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) 

The most likely etiology of SJS/TEN cases is due to few high-risk medications, usually divided into three categories:

1. Strongly associated
2. Associated
3. Suspected association/lower risk

ALDEN stands for 'algorithm of drug causality for epidermal necrolysis'. It is used to determine the offending drug.

The Six-Point Algorithm is available via any search engine. The likelihood of a patient having SJS/TEN is based on the final score:

Score <0 — Very unlikely

Score 0 to 1 — Unlikely

Score 2 to 3 — Possible

Score 4 to 5 — Probable

Score ≥6 — Very probable

#dermatology

#toxicity

         

         

References:

         

1. Clinical Pharmacology and Therapeutics. Sassolas B, Haddad C, Mockenhaupt M, et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther 2010; 88:60. www.nature.com/cpt. Copyright © 2010.

         

         

2. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333:1600.

3. The RegiSCAR Project. Available at: http://www.regiscar.org/index.html (Accessed on May 4, 2025).

HbA1C in ESRD

Q: In end-stage renal Disease (ESRD) patients, Glycated hemoglobin (A1C) is a better reflection of blood glucose control than daily or continuous self-monitoring of blood glucose (SMBG).

A) True

B) False

Answer: B 

In ESRD or patients with high grade renal failure, i.e., estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2, the linear relationship between the average glucose and A1C gets unreliable due to altered red cell turnover, especially in patients who are getting treated with erythropoiesis-stimulating agents (ESAs). Rapid red cell turnover means higher younger red cells, and so the falsely low A1C values. The case was reversed in the past due to analytical interference from carbamylated hemoglobin, which formed due to the elevated urea concentrations. But most labs have abandoned old assay machines.

Another twist to the erratic value of HbA1C comes in patients who are on hemodialysis, as repetitive exposure of the patient's RBCs tends to give high HbA1C levels in even non-diabetic patients.

Either daily glucose monitoring (fingersticks) or continuous glucose monitoring is a better indicator of diabetes control in high-grade or ESRD patients.

#nephrology

#endocrinology

#laboratory-medicine

References:

1. Bloomgarden Z, Handelsman Y. How does CKD affect HbA1c? J Diabetes. 2018 Apr;10(4):270. doi: 10.1111/1753-0407.12624. Epub 2017 Dec 21. PMID: 29124865.

2. Wang X, Peesapati SK, Renedo MF, Moktan S. Hemoglobin A1c levels in non-diabetic patients with end-stage renal disease (ESRD) receiving hemodialysis. J Endocrinol Invest. 2004 Sep;27(8):733-5. doi: 10.1007/BF03347514. PMID: 15636425.

3. Coelho S. What is the Role of HbA1c in Diabetic Hemodialysis Patients? Semin Dial. 2016 Jan-Feb;29(1):19-23. doi: 10.1111/sdi.12408. Epub 2015 Jul 2. PMID: 26138753.

Numbers in calculated Posm formula

Q: Why we multiply Na by 2 in the formula in calculated Plasma osmolalilty whose formula is 2  x  Plasma Na (mEq/L) + [Glucose]/18 + Blood urea nitrogen(BUN)/2.8 ?

Answer: 

The osmolal gap is calculated by subtracting the calculated serum osmolality from the measured serum osmolality. 

High osmolal gap i.e., above 10 mOsm/kg signifies the presence of unmeasured osmoles, like alcohols (ethanol, methanol, isopropanol, or ethylene glycol.) 

The formula for Calculated Posm  =  2  x  Plasma Na (mEq/L) + [Glucose]/18 + Blood urea nitrogen/2.8

Sodium is multiplied by 2 to count for accompanying anions - chloride and bicarbonate.

Glucose is divided by 18 and BUN is divided by 2.8 to convert units of mg/dL into mmol/L. Thats why the corrections for glucose and blood urea nitrogen are not required in countries that report labs in mmol/L.

#laboratory-scienr

#electrolytes

References:

1. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.607.

2. DiNubile MJ. Serum osmolality (letter). N Engl J Med 1984; 310:1609.

3. García-Morales EJ, Cariappa R, Parvin CA, et al. Osmole gap in neurologic-neurosurgical intensive care unit: Its normal value, calculation, and relationship with mannitol serum concentrations. Crit Care Med 2004; 32:986.