Chloride level in sepsis

Q: Which of the following is a prognostic marker of an increase in all-cause hospital mortality in sepsis? - Select one

A) Hyperchloremia 

B) Hypochloremia 

Answer: A

Some clinical and laboratory findings have been identified as markers of mortality in Sepsis. The prominent ones are:

1. Failure to develop a fever or having hypothermia with a temperature below 35.5ºC

2. Leukopenia with a white blood cell count (WBC) less than 4000/mm3, instead of leucocytosis

3. Thrombocytopenia with platelet count <100,000/mm3 

4. Hyperchloremia (Cl ≥110 mEq/L) at 72 hours after ICU admission

                                                     

#sepsis

#ID

                                                     

    

                                                 

References:

                                                     

1. Peres Bota D, Lopes Ferreira F, Mélot C, Vincent JL. Body temperature alterations in the critically ill. Intensive Care Med 2004; 30:811.

2. Neyra JA, Canepa-Escaro F, Li X, et al. Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients. Crit Care Med 2015; 43:1938.

3. Thiery-Antier N, Binquet C, Vinault S, et al. Is Thrombocytopenia an Early Prognostic Marker in Septic Shock? Crit Care Med 2016; 44:764.

multidrug-resistant tuberculosis and QTc prolongation

Q: In the treatment of Multi-Drug resistant Tuberculosis (MDR-TB), which drug requires close monitoring for QTc prolongation? Select one

A) Bedaquiline 

B) Pretomanid 

C) Linezolid 

D) Moxifloxacin 

E) Levofloxacin 

Answer: A

Bedaquiline received full FDA approval in 2024 as part of combination therapy for both adult and pediatric patients (>5 years and ≥15 kg) with pulmonary TB resistant to at least rifampicin and isoniazid (INH).

Bedaquiline can cause QT prolongation, requiring close electrocardiogram (EKG) monitoring before and during the treatment, or as needed if symptoms occur, such as syncope. Patients with higher comorbidities should be watched very closely, such as patients with an underlying history of torsade de pointes, congenital long QT syndrome, hypothyroidism, bradyarrhythmia, uncompensated heart failure, electrolyte disturbances, and those on other drugs prone to cause QTc prolongations. 

Ideally, bedaquiline should be discontinued if QTc-F >500 ms. To make things more complicated, bedaquiline has a terminal serum half-life of four to five months.

#Pharmacology

#ID

#cardiology

References:

1. Katrak S, Lowenthal P, Shen R, True L, Henry L, Barry P. Bedaquiline for multidrug-resistant tuberculosis and QTc prolongation in California. J Clin Tuberc Other Mycobact Dis. 2021 Jan 10;23:100216. doi: 10.1016/j.jctube.2021.100216. PMID: 33598568; PMCID: PMC7868725.

2. World Health Organization. Key updates to the treatment of drug-resistant tuberculosis: rapid communication, June 2024. 2024. https://www.who.int/publications/i/item/B09123 (Accessed on August 25, 2025)

3. Schnippel K, Ndjeka N, Maartens G, et al. Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study. Lancet Respir Med 2018; 6:699.

4. Perrineau S, Lachâtre M, Lê MP, et al. Long-term plasma pharmacokinetics of bedaquiline for multidrug- and extensively drug-resistant tuberculosis. Int J Tuberc Lung Dis 2019; 23:99.

Post MI Q waves

Q: Regression of Q waves after acute myocardial infarction (MI) is a good sign.

A) True

B) False

Answer: A

Pathologic Q waves after MI may regress or disappear entirely following the event, particularly with intervention. Persistence of Q waves after reperfusion is a 'bad sign'. It is associated with a fourfold increase in the risk of congestive heart failure (CHF) or death compared to patients who have regression or resolution of Q-waves. 

Q-wave regression is associated with significantly lower risk of major adverse cardiac events in the future.

#cardiology

#EKG

References:

1. de Framond Y, Schaaf M, Pichot-Lamoureux S, et al. Regression of Q waves and clinical outcomes following primary PCI in anterior STEMI. J Electrocardiol 2022; 73:131.

2. Ramos R, Albert X, Sala J, et al. Prevalence and incidence of Q-wave unrecognized myocardial infarction in general population: Diagnostic value of the electrocardiogram. The REGICOR study. Int J Cardiol 2016; 225:300.

3. Mirvis DM, Goldberger AL. Electrocardiography. In: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 12th ed, Libby P, Bonow RO, Mann DL, et al (Eds), Elsevier, 2022.

Mimickers of AML

Q:  Deficiency of all of the following may mimic Acute Myeloid Leukemia (AML) EXCEPT? - select one

A)    vitamin

B) folate

C) copper 

D) pyridoxine

Answer: D

Deficiency of vitamin B12, folate, or copper can cause megaloblastic leukocytes and profound cytopenias. This may be confused with AML. 

Measurements and other blood work for suspected deficiencies of essential elements and vitamins should be performed.

Pyridoxine leads to microcytic or sideroblastic anemia, but not to megaloblastic anemia.

#hematology

Reference:

1. Konda M, Godbole A, Pandey S, Sasapu A. Vitamin B12 deficiency mimicking acute leukemia. Proc (Bayl Univ Med Cent). 2019 Jul 30;32(4):589-592. doi: 10.1080/08998280.2019.1641045. PMID: 31656431; PMCID: PMC6793970.

2. https://www.uptodate.com/contents/acute-myeloid-leukemia-clinical-manifestations-pathologic-features-and-diagnosis @ uptodate (last access on August 12, 2025)

INH induced seizure

Q: 28 years male has recently started on Isoniazide (INH) after he tested positive for PPD during a routine employment exam. He is now admitted with a seizure. What is the treatment?

Answer: IV Pyridoxine (Vitamin B6)

Five grams of IV pyridoxine given over 5-10 minutes is sufficient to abolish the neurologic effects of isoniazid in most cases. Repeat dosing may be required for persistent seizure activity. Patients usually do not respond to most of the antiepileptics.

#neurology

#pharmacology

References:

1. Tsubouchi K, Ikematsu Y, Hashisako M, Harada E, Miyagi H, Fujisawa N. Convulsive seizures with a therapeutic dose of isoniazid. Intern Med. 2014;53(3):239-42. doi: 10.2169/internalmedicine.53.1303. PMID: 24492693.

2. Minns AB, Ghafouri N, Clark RF. Isoniazid-induced status epilepticus in a pediatric patient after inadequate pyridoxine therapy. Pediatr Emerg Care. 2010 May;26(5):380-1. doi: 10.1097/PEC.0b013e3181db24b6. PMID: 20453796.

Case: Hemoptysis in a young female

Q: 26 years old female presented with hemoptysis. Patient has a previous history of right-sided pneumo-pleural fistula a year ago, which was resolved with chest tube insertion. Bronchoscopy was promptly performed, and the right-sided bronchial tree appeared hyperemic with a friable mucosa. No active source is identified, and cold saline lavage appears to be sufficient. CT chest showed a right-sided focal area of ground-glass opacification. Bronchial artery angiography is reported as no active bleeding but just an "arterial blush". The most probable diagnosis in light of history and presentation is?

Answer: Thoracic endometriosis

Hemoptysis is not common in thoracic endometriosis. Patients who present with hemoptysis are usually younger than patients without hemoptysis (mean age 27 vs 34 years). Hemoptysis is usually catamenial, minor, and right-sided. Massive hemoptysis is rare. Despite typical history, it would be prudent to rule out malignancy by biopsy and pathology.

The thorax is the most frequent site of extra-pelvic endometriosis. Without a histological diagnosis, it should be referred to as 'probable thoracic endometriosis'. Patients with frequent symptomatic presentation require further surgical intervention with blebectomy, pleurodesis, and hormonal suppression. In resistant and debilitating cases, pleurectomy or hysterectomy with bilateral salpingo-oophorectomy (BSO) may be needed.

Cataminal pneumothoraces refer to episodes of pneumothorax corresponding to the menses of the patient; otherwise, they should be called noncataminal pneumothoraces.

See references for further reading.

#pulmonary

#thoracic-surgery

References:

1. Fukuda S, Hirata T, Neriishi K, et al. Thoracic endometriosis syndrome: Comparison between catamenial pneumothorax or endometriosis-related pneumothorax and catamenial hemoptysis. Eur J Obstet Gynecol Reprod Biol 2018; 225:118.

2. Channabasavaiah AD, Joseph JV. Thoracic endometriosis: revisiting the association between clinical presentation and thoracic pathology based on thoracoscopic findings in 110 patients. Medicine (Baltimore) 2010; 89:183.

3. Nezhat C, Main J, Paka C, et al. Multidisciplinary treatment for thoracic and abdominopelvic endometriosis. JSLS 2014; 18.

4. Kim CJ, Nam HS, Lee CY, et al. Catamenial hemoptysis: a nationwide analysis in Korea. Respiration 2010; 79:296.

5. Alifano M, Jablonski C, Kadiri H, et al. Catamenial and noncatamenial, endometriosis-related or nonendometriosis-related pneumothorax referred for surgery. Am J Respir Crit Care Med 2007; 176:1048.

6. Wang HC, Kuo PH, Kuo SH, Luh KT. Catamenial hemoptysis from tracheobronchial endometriosis: reappraisal of diagnostic value of bronchoscopy and bronchial brush cytology. Chest 2000; 118:1205.

7. Tsuboshima K, Kurihara M, Okumura G, et al. Postoperative hormonal therapies reduce the recurrence of thoracic endometriosis-related pneumothorax. Eur J Cardiothorac Surg 2023; 64.

On Hemorrhagic Pericardial & Pleural Effusion

Q: Why does blood in pleural and pericardial fluids not clot?

Answer:  Hemorrhage within the pleural and pericardial space generally does not clot due to 3 reasons.

• mechanical defibrination (movement of lungs and heart)
• activation of fibrinolytic mechanisms
• Also, platelets disappear within hours following hemorrhage

#hematology

References: 

1. Willner DA, Shams P, Grossman SA. Pericardiocentesis. [Updated 2025 Jan 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470347/

2. Kumar S, Verma SK, Singh R, Prasad R. Hemorrhagic pleural effusion secondary to sarcoidosis: A brief review. Ann Thorac Med. 2009 Jan;4(1):27-31. doi: 10.4103/1817-1737.44783. PMID: 19561920; PMCID: PMC2700470.

3. Lending G, El Ghani YA, Kaykov E, Svirsky B, Cohen HI, Altman E. Hemorrhagic Malignant Pleural Effusion: Diagnosis, Survival Rate, and Response to Talc Pleurodesis. Indian J Surg Oncol. 2021 Mar;12(1):54-60. doi: 10.1007/s13193-020-01099-2. Epub 2020 Nov 14. PMID: 33814832; PMCID: PMC7960834.

Ineffective Rx in SS

Q: All of the following should be avoided in Serotonin syndrome (SS) EXCEPT?

A) Propranolol

B) Bromocriptine

C) Dantrolene

D) Lorazepam

Answer: D

In the past, propranolol, bromocriptine, or dantrolene have been suggested in the treatment of SS but were found ineffective or may even harm the patient.

Propranolol has a long duration of action and causes prolonged hypotension. Moreover, it can deceive clinicians by masking tachycardia, which is one of the cardinal signs used to monitor improvement via recommended modalities.

Bromocriptine, being a serotonin agonist, is thought to help in SS but has been found to worsen serotonin syndrome.

Hyperthermia in SS is usually not due to skeletal muscle hyperactivity, and though dantrolene has been used in the past, it has either been ineffective or has no role.

Sedation with "benzos" is recommended in SS.

#neurology

#toxicity

#pharmacology

References:

1. Chiew AL, Isbister GK. Management of serotonin syndrome (toxicity). Br J Clin Pharmacol. 2025 Mar;91(3):654-661. French. doi: 10.1111/bcp.16152. Epub 2024 Jun 26. PMID: 38926083; PMCID: PMC11862804.

2. Nisijima K, Shioda K, Yoshino T, et al. Diazepam and chlormethiazole attenuate the development of hyperthermia in an animal model of the serotonin syndrome. Neurochem Int 2003; 43:155.

BPaL and BPaLM

Q: In multidrug-resistant tuberculosis (MDR)-TB, what do BPaL and BPaLM regimens mean?

Answer: Acronym of drug combination

BPaL

• bedaquiline (B)
• pretomanid (Pa), and 
• linezolid (L)

BPaLM

• bedaquiline (B)
• pretomanid (Pa), and 
• linezolid (L)
• moxifloxacin (M)  -  levofloxacin can be replaced for moxifloxacin -

Regimen is determined by the patient's drug susceptibility, compliance, and underlying comorbidities.

#ID

#pharmacology

#cardiology

References:

Elisa Vanino, Bianca Granozzi, Onno W. Akkerman, Marcela Munoz-Torrico, Fabrizio Palmieri, Barbara Seaworth, Simon Tiberi, Marina Tadolini, - Update of drug-resistant tuberculosis treatment guidelines: A turning point, International Journal of Infectious Diseases, Volume 130, Supplement 1, 2023, Pages S12-S15, ISSN 1201-9712, https://doi.org/10.1016/j.ijid.2023.03.013.

Serum procalcitonin in small bowel obstruction

Q: Procalcitonin is helpful in small bowel obstruction (SBO) to determine conservative vs. surgical approach.

A) True

B) False

Answer: A

There is some weak evidence available that elevated serum procalcitonin levels may be a marker for detecting intestinal strangulation and predicting the need for operative intervention. See a couple of references below.

#surgical-critical-care

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. Ayten R, Dogru O, Camci C, et al. Predictive value of procalcitonin for the diagnosis of bowel strangulation. World J Surg 2005; 29:187.

Adjuvant electrolyte treatment with thiamine administration

Q: Which adjuvant electrolyte treatment is recommended with thiamine administration in Wernick's Encephalopathy (WE)?

Answer: Magnesium

Magnesium is an essential cofactor of thiamine into its active diphosphate and triphosphate forms, and in its absence thiamine may not be utilized appropriately. Although it was established many decades ago, it still frequently gets missed in clinical practice.

It would be prudent to administer magnesium with thiamine in WE. It is common to have Mg deficiency in the presence of required thiamine storage, and refractory WE may precipitate.

#electrolytes

#neurology

#ETOH-abuse

References:

1. Maguire D, Talwar D, Burns A, Catchpole A, Stefanowicz F, Robson G, Ross DP, Young D, Ireland A, Forrest E, Galloway P, Adamson M, Colgan E, Bell H, Orr L, Kerr JL, Roussis X, McMillan DC. A prospective evaluation of thiamine and magnesium status in relation to clinicopathological characteristics and 1-year mortality in patients with alcohol withdrawal syndrome. J Transl Med. 2019 Nov 21;17(1):384. doi: 10.1186/s12967-019-02141-w. PMID: 31752901; PMCID: PMC6873772.

2. Traviesa DC. Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy. J Neurol Neurosurg Psychiatry. 1974 Aug;37(8):959-62. doi: 10.1136/jnnp.37.8.959. PMID: 4420329; PMCID: PMC494812.

3. Zieve L. Influence of magnesium deficiency on the utilization of thiamine. Ann N Y Acad Sci. 1969 Aug 15;162(2):732-43. doi: 10.1111/j.1749-6632.1969.tb13005.x. PMID: 5259566.

hypoxia and pulmonary vessels

Q: Hypoxia causes pulmonary? - select one

A) vasoconstriction

B) vasodilatation

Answer: A

The proper term is hypoxic pulmonary vasoconstriction (HPVC). It is considered a normal regulatory mechanism. When pulmonary or peripheral vessels sense hypoxia, the HPVC mechanism limits blood flow to hypoxic alveoli and preserves ventilation-perfusion matching. 

The learning objective of this question is to understand that both alveolar hypoxia as well as peripheral arterial hypoxemia may cause HPVC. It is time-dependent, i.e., either acute or chronic.

Short-term hypoxia, which occurs over hours or a few days, is reversible with return to normal oxygen level or with oxygen administration.

Chronic hypoxia, which occurs over weeks, is often only partially reversible and leads to Group-3 pulmonary hypertension.

#pulmonary

References:

1. Dunham-Snary KJ, Wu D, Sykes EA, Thakrar A, Parlow LRG, Mewburn JD, Parlow JL, Archer SL. Hypoxic Pulmonary Vasoconstriction: From Molecular Mechanisms to Medicine. Chest. 2017 Jan;151(1):181-192. doi: 10.1016/j.chest.2016.09.001. Epub 2016 Sep 16. PMID: 27645688; PMCID: PMC5310129.

2. Sylvester JT, Shimoda LA, Aaronson PI, Ward JP. Hypoxic pulmonary vasoconstriction. Physiol Rev. 2012 Jan;92(1):367-520. doi: 10.1152/physrev.00041.2010. Erratum in: Physiol Rev. 2014 Jul;94(3):989. PMID: 22298659; PMCID: PMC9469196.

Diagnosis of Hypertensive Encephelopathy

Q: Hypertensive encephalopathy, by definition, is a diagnosis of exclusion.

A) True

B) False

Answer: A

Hypertensive encephalopathy occurs due to severe and/or sudden rises in Blood Pressure (BP), resulting in cerebral edema. Hypertensive encephalopathy, by definition, is a diagnosis of exclusion. This is a fundamental concept as it requires all other suspected diagnoses to be ruled out first. An increase in BP may be secondary to other underlying pathophysiology, which may require primary attention.

In terms of management, it is not recommended to drop BP drastically in hypertensive encephalopathy. In the first 24 hours, it is not prudent to drop mean (or systolic) BP more than 15 percent. Patient who have chronic hypertension have their cerebral blood flow shifted to the right, and should not attempt to correct acutely, which may result in cerebral herniation. It's a simple graph, but immensely essential to keep the visual always.

#hemodynamics

#neurology

References:

1. Miller JB, Suchdev K, Jayaprakash N, Hrabec D, Sood A, Sharma S, Levy PD. New Developments in Hypertensive Encephalopathy. Curr Hypertens Rep. 2018 Feb 26;20(2):13. doi: 10.1007/s11906-018-0813-y. PMID: 29480370.

2. Balahura AM, Moroi ȘI, Scafa-Udrişte A, Weiss E, Japie C, Bartoş D, Bădilă E. The Management of Hypertensive Emergencies-Is There a "Magical" Prescription for All? J Clin Med. 2022 May 31;11(11):3138. doi: 10.3390/jcm11113138. PMID: 35683521; PMCID: PMC9181665.

Bell Clapper and Blue Dot Signs

Case 17 years old male presented with acute pain in the Right testicular area, progressively worsening over the last 4 hours. On exam, "bell clapper" deformity is noted. Also, the "blue dot" sign is noted on the scrotal wall.

Diagnosis: Testicular torsion 

Bell clapper deformity is a congenital abnormality that makes it more prone to twisting (torsion). The affected testis may be elevated due to shortening of the spermatic cord, or it may lie horizontally, known as bell clapper deformity. 

Also, the "blue dot" sign may be noted on the scrotal wall. Although not common, it strongly suggests the torsion.

Testicular torsion is a surgical emergency. Immediate bedside POCUS ultrasound should be performed, and an emergent urological consult should be obtained.

#surgical-critical-care

#urology

References:

1. Nassiri N, Zhu T, Asanad K, Vasquez E. Testicular Torsion From Bell-clapper Deformity. Urology. 2021 Jan;147:275. doi: 10.1016/j.urology.2020.06.045. Epub 2020 Jul 7. PMID: 32650017.

2. Khan F, Muoka O, Watson GM. Bell clapper testis, torsion, and detorsion: a case report. Case Rep Urol. 2011;2011:631970. doi: 10.1155/2011/631970. Epub 2011 Sep 19. PMID: 22606621; PMCID: PMC3350281.

3. Laher A, Ragavan S, Mehta P, Adam A. Testicular Torsion in the Emergency Room: A Review of Detection and Management Strategies. Open Access Emerg Med. 2020 Oct 12;12:237-246. doi: 10.2147/OAEM.S236767. PMID: 33116959; PMCID: PMC7567548.

Vaso in cocaine overdose

Q: Why is vasopressin preferable over epinephrine in cardio-pulmonary arrest due to cocaine overdose?

Answer: Epinephrine, like cocaine, has alpha-adrenergic effects. Because of this similarity in the cardiovascular effects, the administration of epinephrine to a patient who arrests in a hyperadrenergic state has been like "pouring gasoline over fire."

Moreover, cocaine prevents the reuptake of exogenously administered epinephrine. Therefore, if epinephrine is used, AHA Guidelines recommend that high-dose epinephrine should be avoided and that the interval for its administration be increased.

Vasopressin offers considerable advantages over epinephrine in cardiac arrest secondary to cocaine toxicity. The hyperadrenergic state caused by cocaine increases myocardial oxygen demand, and vasopressin increases coronary blood flow and thereby myocardial oxygen availability.

Also, cocaine toxicity causes acidosis and epinephrine loses much of its effectiveness in an acidotic environment, whereas vasopressin demonstrates good efficacy even with severe acidosis.

#hemodynamic

#toxicity

Recommended readings:

1. Sofuoglu M, Nelson D, Babb DA, Hatsukami DK. Intravenous cocaine increases plasma epinephrine and norepinephrine in humans. Pharmacol Biochem Behav. 2001 Mar;68(3):455-9. doi: 10.1016/s0091-3057(01)00482-8. PMID: 11325399.

2. Richards JR, Garber D, Laurin EG, Albertson TE, Derlet RW, Amsterdam EA, Olson KR, Ramoska EA, Lange RA. Treatment of cocaine cardiovascular toxicity: a systematic review. Clin Toxicol (Phila). 2016 Jun;54(5):345-64. doi: 10.3109/15563650.2016.1142090. Epub 2016 Feb 26. PMID: 26919414.

VIR and opioids

Q: Vancomycin Infusion Reaction (VIR) (Red Man Syndrome) can be attenuated by simultaneous administration of morphine.

A) True

B) False

Answer: B (False)

VIR, by definition (though IgE-mediated reaction is possible with previous exposure), is a dose- or rate-related mast cell degranulation. This mast cell degranulation gets enhanced or accelerated by the simultaneous administration of opioids like morphine, meperidine, or codeine. Interestingly, this risk is way less and can be an exception in fentanyl, which rarely induces histamine release.

Other known medications to enhance VIR are radiocontrast dye, some muscle relaxants like succinylcholine, atracurium, cisatracurium, doxacurium, mivacurium, tubocurarine, dextran, polygeline, and ciprofloxacin.

#pharmacology

# allergy-immunology

References:

1. Wong JT, Ripple RE, MacLean JA, et al. Vancomycin hypersensitivity: synergism with narcotics and "desensitization" by a rapid continuous intravenous protocol. J Allergy Clin Immunol 1994; 94:189.

2. Wazny LD, et al. Desensitization protocols for vancomycin hypersensitivity. The Annals of Pharmacotherapy 2001; 35:1458. Copyright © 2001 Harvey Whitney.

3. Alvarez-Arango S, Ogunwole SM, Sequist TD, Burk CM, Blumenthal KG. Vancomycin Infusion Reaction - Moving beyond "Red Man Syndrome". N Engl J Med. 2021 Apr 8;384(14):1283-1286. doi: 10.1056/NEJMp2031891. Epub 2021 Apr 3. PMID: 33830710; PMCID: PMC9235042.

4. Zhu LJ, Liu AY, Wong PH, Arroyo AC. Road Less Traveled: Drug Hypersensitivity to Fluoroquinolones, Vancomycin, Tetracyclines, and Macrolides. Clin Rev Allergy Immunol. 2022 Jun;62(3):505-518. doi: 10.1007/s12016-021-08919-5. Epub 2022 Jan 29. PMID: 35092578; PMCID: PMC9167562.

IV Digoxin

Q: You wrote an order for intravenous (IV) Digoxin 0.25 mg. What is missing in this order? 

 Answer; Rate 

IV Digoxin should be given over at least 5 minutes. Rapid infusion of Digoxin (digitalis) may cause coronary as well as arteriolar constriction, which may induce cardiac ischemia or make it worse. 

 Also, it is not advisable to administer digoxin simultaneously in the same intravenous line as with other drips/drugs. 

 Another essential reminder - Digoxin level should be measured just before the next scheduled dose (trough) or at least 6 to 8 hours after the last dose, to allow adequate time for equilibration of digoxin between serum and tissue. 

 #pharmacology 

#cardiology

 References: 

 1. Digoxin Injection: Package Insert / Prescribing Info - link: https://www.drugs.com/pro/digoxin-injection.html (last accessed: August 12, 2025) 

 2. Greenblatt DJ, Duhme DW, Koch-Weser J, Smith TW. Intravenous digoxin as a bioavailability standard: slow infusion and rapid injection. Clin Pharmacol Ther. 1974 May;15(5):510-3. doi: 10.1002/cpt1974155510. PMID: 4827467.

Cryoprecipitate

Q: Why do we call it cryoprecipitate?

Answer: 

The name explains everything. Cryoprecipitate means "cold precipitate". When FFP is thawed slowly at 4 °C, a white precipitate forms at the bottom of the bag, which can then be separated from the supernatant plasma. This precipitate is rich in fibrinogen, factor VIII, von Willebrand factor, factor XIII, and fibronectin - and is called cryoprecipitate. 

One unit of cryoprecipitate is derived from fresh frozen plasma (FFP) prepared from a unit of whole blood. As there is only a little precipitate at the bottom of the bag, 1 unit of cryoprecipitate comprises only a volume of 10-20 mL. Contents:

• 80-100 units of factor VIII, which consists of both the procoagulant activity and the von Willebrand factor,
• 150-250 mg of fibrinogen,
• 50-100 units of factor XIII, and
• 50-60 mg of fibronectin.

Half life is about one year if stored at-18 °C. When ordered (generally given as 6 units at a time), cryoprecipitate is thawed back to 37 °C. Once thawed, it must be kept at room temperature and has an expiration time of 4 to 6 hours.

#hematology

#transfusion-medicine

References:

1. Nascimento B, Goodnough LT, Levy JH. Cryoprecipitate therapy. Br J Anaesth. 2014 Dec;113(6):922-34. doi: 10.1093/bja/aeu158. Epub 2014 Jun 27. PMID: 24972790; PMCID: PMC4627369.

2. Callum JL, Karkouti K, Lin Y. Cryoprecipitate: the current state of knowledge. Transfus Med Rev. 2009 Jul;23(3):177-88. doi: 10.1016/j.tmrv.2009.03.001. PMID: 19539873.

Smoke on TEE

Q: What does the finding of spontaneous echocardiographic contrast (SEC) or "smoke" signify on transesophageal echocardiogram (TEE)?

Answer: 

Spontaneous echocardiographic contrast (SEC), popularly known as "smoke," refers to the presence of dynamic, smoke-like echoes seen during TEE, mainly in the left atrium, but can be seen in any chamber.

SEC signifies increased erythrocyte aggregation caused by low shear rate due to altered flow dynamics. Erythrocyte aggregation is mediated by plasma proteins, especially fibrinogen, which promotes red cell rouleaux formation by moderating the normal electrostatic forces (due to negatively charged membranes) that keep erythrocytes from aggregating. SEC is usually a preceding stage of thrombus formation.

#cardiology

References:

1. Black IW, Chesterman CN, Hopkins AP, et al. Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation. J Am Coll Cardiol 1993; 21:451.

2. Gedikli Ö, Mohanty S, Trivedi C, Gianni C, Chen Q, Della Rocca DG, Burkhardt JD, Sanchez JE, Hranitzky P, Gallinghouse GJ, Al-Ahmad A, Horton R, Di Biase L, Natale A. Impact of dense "smoke" detected on transesophageal echocardiography on stroke risk in patients with atrial fibrillation undergoing catheter ablation. Heart Rhythm. 2019 Mar;16(3):351-357. doi: 10.1016/j.hrthm.2018.10.004. Epub 2018 Oct 9. PMID: 30312757.

3. Fatkin D, Loupas T, Low J, Feneley M. Inhibition of red cell aggregation prevents spontaneous echocardiographic contrast formation in human blood. Circulation 1997; 96:889.

4. Black IW. Spontaneous echo contrast: where there's smoke there's fire. Echocardiography. 2000 May;17(4):373-82. doi: 10.1111/j.1540-8175.2000.tb01153.x. PMID: 10979010.

Acid-Base in hepatic encephalopathy

Q; 52 years old male with Grade 0 hepatic encephalopathy is intubated due to pneumonia. Is it good or bad to keep PH on the alkalotic side? - choose one

A) Good

B) Bad

Answer: B 

Alkalosis may facilitate the conversion of Ammonium to Ammonia ( NH4 + to NH3). An increase in Ammonia levels will make hepatic encephalopathy worse. There are 4 grades of hepatic encephelopathy but various factors may make it worse or better.

Grade 0 - Minimal hepatic encephalopathy (subclinical). Lack of detectable changes.

Grade 1 - Trivial lack of awareness. Shortened attention span. Impaired addition or subtraction. Hypersomnia, insomnia, or inversion of sleep pattern. Irritability. Mild confusion. Slowing of the ability to perform mental tasks.

Grade 2 - Lethargy. Disorientation. Inappropriate behavior. Slurred speech. Obvious asterixis.

Grade 3 - Somnolent but can be aroused.

Grade 4 - Coma with or without response to painful stimuli

#acid-base

#hepatology

#neurology

References:

1. Kabbani AR, Tergast TL, Manns MP, Maasoumy B. Alkalose, Albumin, Ammoniak und die hepatische Enzephalopathie [Alkalosis, albumin, ammonia and hepatic encephalopathy]. Med Klin Intensivmed Notfmed. 2021 May;116(4):358-359. German. doi: 10.1007/s00063-021-00812-5. PMID: 33825943.

2. James IM, Sampson D, Nashat S, Williams HS, Garassini M. Effect of induced metabolic alkalosis in hepatic encephalopathy. Lancet. 1969 Nov 22;2(7630):1106-8. doi: 10.1016/s0140-6736(69)90706-5. PMID: 4186996.

Glucagon in bradycardia

Q: Intravenous (IV) glucagon should be administered in suspected cases of?- select one

A) beta blocker (BB) overdose

B) calcium channel blocker (CCB) overdose 

C) both BB and CCB overdoses

Answer: C

Both BB and CCM overdoses require IV glucagon with a bolus dose of 3 to 10 mg over five minutes, and if the condition persists, with a continuous infusion dose of 3 to 5 mg per hour. This can be titrated by monitoring the blood pressure (BP) response, more than the heart rate (HR) response, with an ultimate objective of sustained hemodynamics. Some experts argue that glucagon only helps in increasing the HR but not the BP, so other modalities, which should be tried first, such as atropine (in acute situations), IV calcium, or a temporary pacemaker. Glucagon should be used either as an adjuvant or a second line of treatment.

Glucagon activates adenylate cyclase, causing an increase in adenosine 3'-5'-cyclic monophosphate (cAMP). Elevations in cAMP increase the intracellular pool of calcium available for release during depolarization, augmenting contractility.

Two major caveats of using Glucagon are severe vomiting, which may require simultaneous administration of an anti-emetic like ondansetron. The second caveat is tachyphylaxis with IV infusion.

#toxicology

#pharmacology

#cardiology

References:

1. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51.

2. Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol 2003; 41:595.

3. Mahr NC, Valdes A, Lamas G. Use of glucagon for acute intravenous diltiazem toxicity. Am J Cardiol 1997; 79:1570.

4. Senart AM, LeClair LA. Cardiovascular and Adverse Effects of Glucagon for the Management of Suspected Beta Blocker Toxicity: a Case Series. J Med Toxicol 2023; 19:9.

Milrinone MOA

Q: Milrinone is a(n)? - Select one

A) arteriolar dilator

B) Venodilator 

Answer: B

Milrinone has a minimal venodilation effect. In fact, it's a pure arterial dilator. This explains its good effect on pulmonary arteries as a good afterload reducer for the right heart.

#hemodynamics

#pharmacology

References:

1. Ayres JK, Maani CV. Milrinone. 2023 Aug 28. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30422538.

2. de Miranda ML, Pereira SJ, Santos AO, Villela NR, Kraemer-Aguiar LG, Bouskela E. Milrinone attenuates arteriolar vasoconstriction and capillary perfusion deficits on endotoxemic hamsters. PLoS One. 2015 Feb 3;10(2):e0117004. doi: 10.1371/journal.pone.0117004. PMID: 25646813; PMCID: PMC4315607.

3. Shipley JB, Tolman D, Hastillo A, Hess ML. Milrinone: basic and clinical pharmacology and acute and chronic management. Am J Med Sci. 1996 Jun;311(6):286-91. doi: 10.1097/00000441-199606000-00011. PMID: 8659556.

GCS and severity of TBI

Q: The severity of Traumatic Brain Injury (TBI) is defined by a Glasgow Coma Scale (GCS) score less than ___________. 

Answer; 9

Strictly by definition, a GCS <9 is considered  'severe TBI' and calls for intubation. 

That said, a clinician's assessment and judgment often supersede many decisions.

  

#neuro-surgery

#trauma

References:

1. Foulkes MA, Eisenberg HM, Jane JA, et al. The Traumatic Coma Data Bank: design, methods, and baseline characteristics. J Neurosurg 1991; 75:S8.

2. Carney N, Totten AM, O'Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery 2017; 80:6.

ICP lowering agents and rebound phenomenon

Q: Which of the following can have the highest "rebound effect" during the management of high Intracranial Pressure(ICP)? - select one

A) Mannitol 

B) Furosemide

C) Glycerol 

D) Urea

Answer: C

All of the above agents have been used in the management of high ICP; however, mannitol remains the leading agent and is considered the standard.

'Rebound phenomenon' may occur after repeated administration of mannitol and glycerol, when these agents reenter the brain through a damaged blood-brain barrier and reverse the osmotic gradient. This requires continued monitoring of serum sodium, serum osmolality, and renal function even after these agents are discontinued. Serum sodium >150 mEq, serum osmolality >320 mOsm, significant hypotension, or evidence of evolving acute tubular necrosis (ATN) should lead a clinician to consider the stoppage of these osmotic diuretics.

Glycerol and urea have been tried in the past with the hope that they work more quickly than mannitol, but have fallen out of favor as they can have a significant rebound effect, particularly with glycerol. Additionally, glycerol is less effective in ICP control.

Furosemide, administered intravenously at 0.5 to 1.0 mg/kg, has been combined with mannitol to enhance its effect; however, dehydration and hypokalemia may limit its use.

#neuro-critical-care

References: 

1. Chesnut RM, Marshall LF. Management of head injury. Treatment of abnormal intracranial pressure. Neurosurg Clin N Am 1991; 2:267.

2. Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg 1992; 77:584.

3. Pollay M, Fullenwider C, Roberts PA, Stevens FA. Effect of mannitol and furosemide on blood-brain osmotic gradient and intracranial pressure. J Neurosurg 1983; 59:945.

4. Otvos B, Kshettry VR, Benzel EC. The history of urea as a hyperosmolar agent to decrease brain swelling. Neurosurg Focus. 2014 Apr;36(4):E3. doi: 10.3171/2014.1.FOCUS13558. PMID: 24684336.

5. Node Y, Nakazawa S. Clinical study of mannitol and glycerol on raised intracranial pressure and on their rebound phenomenon. Adv Neurol 1990; 52:359.

Systemic Complications Following SAH

Q: All of the following are likely to be the complications of SubArachnoid Hemmorhage (SAH) EXCEPT?

A) Rebleeding

B) Vasospasm 

C) Increased intracranial pressure (ICP)

D) Seizures

E) Hypernatremia

Answer: E

Vasospasm is the most dreaded and dramatic complication of SAH, but fortunately, it can be managed in the ICU, where 24/7 care is provided. About one out of five patients experience it, particularly with diffuse SAH.

Rebleeding and Increased ICP are also expected, and usually successfully managed in the ICU.

Prescription of anti-seizure medications is the norm.

All complications from Choices A to D are expected in NASAH, but hyponatremia is expected instead of hypernatremia. Interestingly, the occurrence of hyponatremia increases the risk of vasospasm.

#neurology

#neuro-surgery

#surgical-critical-care

References:

1. Gillespie CS, Mihaela-Vasilica A, Dhaliwal J, Lee KS, Henney AE, Veremu M, Chedid Y, Roman E, Al-Nusair L, Ekert JO, China M, Cook WH, Alam AM, Ashraf M, Funnell JP, Grandidge C, Best L, Matloob S. Hyponatremia Incidence After Subarachnoid Hemorrhage and Association with Outcomes: Systematic Review and Meta-Analysis. World Neurosurg. 2025 Mar;195:123616. doi: 10.1016/j.wneu.2024.123616. Epub 2025 Jan 31. PMID: 39732459.

2. Garg R, Bar B. Systemic Complications Following Aneurysmal Subarachnoid Hemorrhage. Curr Neurol Neurosci Rep. 2017 Jan;17(1):7. doi: 10.1007/s11910-017-0716-3. PMID: 28168536.

CT scan in CVT

Q; 32 years old recently postpartum patient presented with severe headache. Neuroradiologist called with concern for cerebral venous thrombosis (CVT). Which three radiological signs on a CT scan raise the concern for CVT?

Answer:

In CVT, history plays a pivotal role. Females are three times more prone to develop CVT due to a higher risk in a few situations, such as the postpartum period. Symptoms usually lead to a CT scan of the head as the first test. It may show focal areas of edema or venous infarction, cortical or juxtacortical hemorrhage, diffuse brain edema, and hyperdensities suggestive of venous occlusion.

A clinician should look for three signs:

• Dense triangle sign – triangular or round hyperdensity on a cross-section at the site of a sinus.
• Empty delta sign (also called the empty triangle or negative delta sign) – triangular hyperdensity surrounding a hypo-/iso-dense central region within the superior sagittal sinus on head CT performed with contrast.
• Cord sign – a curvilinear or linear hyperdensity typically found at the surface of the cerebral cortex.

Serial CT scans can be interesting with "vanishing infarcts", where some lesions may disappear and new lesions may appear.

On the same token, another interesting phenomenon to be observed is the H:H ratio, i.e., the Hounsfield unit (HU) to hematocrit ratio. It compares the density of the blood in the dural sinuses (measured in HU) to the patient's hematocrit level. A higher H:H ratio suggests a higher likelihood of CVT. 

MRI should be performed.

As expected, consultation with neurology and neurosurgery is recommended.

#neurology

#neurosurgery

@radiology

References:

1. Otite FO, Patel S, Sharma R, et al. Trends in incidence and epidemiologic characteristics of cerebral venous thrombosis in the United States. Neurology 2020; 95:e2200.

2. Lee EJ. The empty delta sign. Radiology 2002; 224:788.

3. Boukobza M, Crassard I, Bousser MG. When the "dense triangle" in dural sinus thrombosis is round. Neurology 2007; 69:808.

4. Buyck PJ, De Keyzer F, Vanneste D, et al. CT density measurement and H:H ratio are useful in diagnosing acute cerebral venous sinus thrombosis. AJNR Am J Neuroradiol 2013; 34:1568.

radioactive iodine uptake and thyrotoxicosis factitia

Q; 32 years old female with previous history of Anorexia Nervosa presents with signs and symptoms of thyrotoxicosis. 'Thyrotoxicosis factitia' is highly suspected as no exophthalmos was noted. A low TSH level is found, along with normal free T4 and T3 levels. 24-hour radioiodine uptake ordered. Which of the following may help in confirming the diagnosis?

A) High 24-hour radioiodine uptake

B) Low 24-hour radioiodine uptake

Answer: B

There are many clinical situations, besides the intentional or unintentional intake of exogenous thyroid hormone, that may cause thyrotoxicosis factitia. It includes thyroid cancer, which may require suppressive doses of thyroxine to minimize TSH stimulation of tumor growth, and a higher-than-usual dose prescribed to shrink the thyroid gland. Also, psychiatric disorders are prone to low levels of TSH, and thyroid hormone may be prescribed in combination with antipsychotics. 

Besides history and thyroid hormone levels, the 24-hour radioiodine uptake in the thyroid is nearly absent in patients with exogenous hyperthyroidism due to the suppression of TSH secretion. The only caveat to this confirmatory test is the presence of autonomous functioning thyroid tissue elsewhere in the body, or thyroiditis with the release of preformed hormone from any inflamed gland, such as struma ovarii, and due to iodine-induced hyperthyroidism. 

#endocrinology

#nuclear-medicine

References:

1. Cohen JH 3rd, Ingbar SH, Braverman LE. Thyrotoxicosis due to ingestion of excess thyroid hormone. Endocr Rev 1989; 10:113.

2. Vorasart P, Sriphrapradang C. Factitious thyrotoxicosis: how to find it. Diagnosis (Berl). 2020 May 26;7(2):141-145. doi: 10.1515/dx-2019-0015. PMID: 30927742.

3. Ross DS. Syndromes of thyrotoxicosis with low radioactive iodine uptake. Endocrinol Metab Clin North Am. 1998 Mar;27(1):169-85. doi: 10.1016/s0889-8529(05)70305-4. PMID: 9534035.

Metformin and AAA

Q: Metformin has a protective effect on Abdominal Aortic Aneurysm (AAA).

A) True

B) False

Answer: A

Overall, diabetes mellitus has been negatively associated with AAA. Many of us may find this counterintuitive, but this can be explained by the fact that atherosclerosis and AAA are two different pathophysiology. The odds ratio of AAA among patients with diabetes compared with nondiabetics is remarkably around 0.52 and 0.75.

Upon further examination of this data, one possible reason may be the protective effect of anti-diabetic medications, particularly Metformin, which independently reduces inflammatory markers in vitro and AAA growth in human studies. Other meds used in Diabetes, such as statins, angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), fenofibrate, and some hypoglycemic agents, also have a potential modest protection on AAA.

#cardiovascular

#Endocrine

#pharmacology

#epidemiology

References:

1. Kent KC, Zwolak RM, Egorova NN, et al. Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. J Vasc Surg 2010; 52:539.

2. Shantikumar S, Ajjan R, Porter KE, Scott DJ. Diabetes and the abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 2010; 39:200.

3. Aune D, Schlesinger S, Norat T, Riboli E. Diabetes mellitus and the risk of abdominal aortic aneurysm: A systematic review and meta-analysis of prospective studies. J Diabetes Complications 2018; 32:1169.

4. Pafili K, Gouni-Berthold I, Papanas N, Mikhailidis DP. Abdominal aortic aneurysms and diabetes mellitus. J Diabetes Complications 2015; 29:1330.

5. Raffort J, Hassen-Khodja R, Jean-Baptiste E, Lareyre F. Relationship between metformin and abdominal aortic aneurysm. J Vasc Surg 2020; 71:1056.

Diagnosis of EVALI

Q: All of the following are used to confirm or to designate probable diagnosis of E-cigarette or vaping product use-associated lung injury (EVALI) EXCEPT?

A) Use of an e-cigarette or related product in the last 3 months

B) Lung opacities on chest radiograph or CT

C) Exclusion of lung infection by objective diagnostic means

D) Clinical signs (Fever, Tachycardia, or Shortness of Breath)

E) Absence of a likely alternative diagnosis

Answer: D

The criteria to confirm EVALI require four components:

• History of E-Cigarette use by any modality in the last 90 days
• Lung opacities either on CXR ot CT scan
• Exclusion of lung infection via viral respiratory panel, COVID-19 test, urine antigen tests, blood cultures, sputum culture, bronchoalveolar lavage (BAL), and/or HIV-related opportunistic infections.
• Absence of an alternative diagnosis (eg, cardiac, neoplastic, rheumatologic)

If infection cannot be excluded with certainty, it should be labeled as "probable diagnosis of EVALI."

#pulmonary

#ID

References:

1. Layden JE, Ghinai I, Pray I, et al. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report. N Engl J Med 2020; 382:903.

2. Schier JG, Meiman JG, Layden J, et al. Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use - Interim Guidance. MMWR Morb Mortal Wkly Rep 2019; 68:787.

3. Tituana NY, Clavijo CG, Espinoza EF, Tituana VA. E-cigarette use-associated lung injury (EVALI). Pneumologie. 2024 Jan;78(1):58-69. doi: 10.1055/a-2161-0105. Epub 2023 Oct 19. PMID: 37857323; PMCID: PMC10791482.

4. Sund LJ, Dargan PI, Archer JRH, Wood DM. E-cigarette or vaping-associated lung injury (EVALI): a review of international case reports from outside the United States of America. Clin Toxicol (Phila). 2023 Feb;61(2):91-97. doi: 10.1080/15563650.2022.2160342. Epub 2023 Jan 13. PMID: 36636876.