Albumin and CIP

Q: Low serum albumin is a risk factor for Critical Illness Polyneuropathy (CIP).

A) True

B) False

Answer: A

CIP is commonly seen in patients who stay in the ICU for more than a week or two. Some of the known risk factors are:

• severe sepsis 
• severe systemic inflammatory response syndrome (SIRS)
• persistently elevated blood glucose
• low serum albumin 
• use of neuro-muscular blockade

Use of steroids is found to be more associated with Critical Illness Myopathy (CIM), though most patients in the ICU have a combined CIM and CIP.

#neurology

#icu-course

References:

1. Witt NJ, Zochodne DW, Bolton CF, et al. Peripheral nerve function in sepsis and multiple organ failure. Chest 1991; 99:176.

2. Zhou C, Wu L, Ni F, Ji W, Wu J, Zhang H. Critical illness polyneuropathy and myopathy: a systematic review. Neural Regen Res. 2014 Jan 1;9(1):101-10. doi: 10.4103/1673-5374.125337. PMID: 25206749; PMCID: PMC4146320.

3. Bednarík J, Vondracek P, Dusek L, Moravcova E, Cundrle I. Risk factors for critical illness polyneuromyopathy. J Neurol. 2005 Mar;252(3):343-51. doi: 10.1007/s00415-005-0654-x. Epub 2005 Mar 30. PMID: 15791390.

4. Atrash AK, de Vasconcellos K. Low albumin levels are associated with mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit. South Afr J Crit Care. 2020 Dec 1;36(2):10.7196/SAJCC.2020.v36i2.422. doi: 10.7196/SAJCC.2020.v36i2.422. PMID: 35493283; PMCID: PMC9045521.

Parovirus 19 fetal severe anemia

Q: A 24-year-old female with 22 weeks of pregnancy is admitted to the ICU with severe symptoms of Parvovirus 19, confirmed with a high IgM titer but a negative IgG titer. There is a severe fetal anemia, and thrombocytopenia is suspected. How should the blood transfusion be given? -select one

A) Slow Intravenous 

B) Intrauterine

C) Plasmapheresis

Answer: B

Usually, a fetus can handle mild to moderate anemia without any major intervention. Severe fetal anemia can lead to hydrops fetalis. Noninvasive methods to detect fetal anemia are:

• Doppler middle cerebral artery (MCA) peak systolic velocity (PSV), and 
• ductus venosus velocity  

Invasively, cord blood sampling can be performed via percutaneous umbilical venous sampling, but is reserved for suspected severe cases requiring intervention.

Interesting, blood transfusions in such situations are given directly via intrauterine. Intrauterine transfusion is possible only after 18 weeks of pregnancy due to the small vessel size prior to it.

The authors of this question highly encouraged students to review reference #4 below.

#Ob-gyn

References:

1. Fairley CK, Smoleniec JS, Caul OE, Miller E. Observational study of effect of intrauterine transfusions on outcome of fetal hydrops after parvovirus B19 infection. Lancet 1995; 346:1335.

2. Rodis JF, Borgida AF, Wilson M, et al. Management of parvovirus infection in pregnancy and outcomes of hydrops: a survey of members of the Society of Perinatal Obstetricians. Am J Obstet Gynecol 1998; 179:985.

3. von Kaisenberg CS, Jonat W. Fetal parvovirus B19 infection. Ultrasound Obstet Gynecol 2001; 18:280.

4. Devlieger R, Vergote S, Van den Eede E, Haenen K, Lewi L. Intrauterine transfusion: Best practices, techniques, and evolving trends. Best Pract Res Clin Obstet Gynaecol. 2026 Feb;104:102686. doi: 10.1016/j.bpobgyn.2025.102686. Epub 2025 Nov 20. PMID: 41289715.

NPPE - MOA

Case: 22 years old atheletic male went through a non-complicated appendectomy under general anesthesia. Patient became agitated on weaning sedation and started biting on the endotracheal tube (ETT). The patient was extubated, but on extubation developed severe pulmonary edema with desaturation. Patient recovered well with supplemental oxygen, non-invasive positive pressure ventilation (NIPPV), diuresis, and infusion of Dexmedetomidine, and was eventually extubated without complications. Why is post-extubation pulmonary edema called negative pressure pulmonary edema (NPPE)?

Answer: Post-extubation pulmonary edema is a common phenomenon in the PACU/ICU if a patient forcibly inhales against a closed glottis. This is also known as the Mueller or reverse Valsalva maneuver. This phenomenon occurs post-extubation due to laryngospasm, pharyngeal obstruction, or biting of the endotracheal tube during extubation. 

Conventional teaching holds that it occurs immediately, though this is not entirely true; a delayed NPPE has been reported up to 12 hours after extubation. People with obesity, short neck, obstructive sleep apnea, or acromegaly are at the highest risk, followed by young, healthy, athletic adults.

The correct term is negative pressure pulmonary edema, which refers to a non-cardiac form of pulmonary edema resulting from the development of negative interstitial pressure around the capillaries, drawing intravascular fluid into the interstitial space.

#procedure

#pulmonary

References:

1. Mulkey Z, Yarbrough S, Guerra D, et al. Postextubation pulmonary edema: a case series and review. Respir Med 2008; 102:1659.

2. Holmes JR, Hensinger RN, Wojtys EW. Postoperative pulmonary edema in young, athletic adults. Am J Sports Med 1991; 19:365.

3. Tsai PH, Wang JH, Huang SC, Lin YK, Lam CF. Characterizing post-extubation negative pressure pulmonary edema in the operating room-a retrospective matched case-control study. Perioper Med (Lond). 2018 Dec 6;7:28. doi: 10.1186/s13741-018-0107-6. PMID: 30534363; PMCID: PMC6282297.

PG

Q: A 43-year-old male with an established history of ulcerative colitis is admitted to the ICU with Lower GI bleed requiring transfusion. On physical exam, chronic ulceration was noted on the lower extremity and diagnosed as Pyoderma gangrenosum (PG). PG, as the name suggests, is an infectious process causing gangrene.

A) True

B) False

Answer: B

Pyoderma gangrenosum (PG) is a misnomer as it is neither an infectious nor a gangrenous condition! The probability of this misnomer arises from its striking, infectious-like appearance.

PG is a neutrophilic dermatosis that presents as an inflammatory, ulcerative skin disorder. The most common presentation of PG is an inflammatory papule or pustule that progresses to a painful ulcer with a violaceous, undermined border and a purulent base. It may also present with bullous, vegetative, peristomal, and extracutaneous lesions.

Clinical Significance: It has high association with an underlying systemic diseases like inflammatory bowel disease, hematologic disorders, and arthritis.

#dermatology

References:

1. Maverakis E, Marzano AV, Le ST, Callen JP, Brüggen MC, Guenova E, Dissemond J, Shinkai K, Langan SM. Pyoderma gangrenosum. Nat Rev Dis Primers. 2020 Oct 8;6(1):81. doi: 10.1038/s41572-020-0213-x. PMID: 33033263.

2. Łyko M, Ryguła A, Kowalski M, Karska J, Jankowska-Konsur A. The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives. Int J Mol Sci. 2024 Feb 19;25(4):2440. doi: 10.3390/ijms25042440. PMID: 38397117; PMCID: PMC10889749.

3. Moltrasio C, Romagnuolo M, Tavoletti G, Maronese CA, Marzano AV. Pyoderma gangrenosum: pathogenetic mechanisms and their implications for treatment. Semin Immunopathol. 2025 Oct 23;47(1):38. doi: 10.1007/s00281-025-01064-7. PMID: 41128863; PMCID: PMC12549756.

iNO and organ dysfunction

Q: Prolonged use of inhaled Nitric Oxide (iNO) is intended to cause more of? - select one

A) Kidney dysfunction

B) liver dysfunction

Answer: A

Prolonged use of iNO beyond 5-7 days may increase the risk of acute kidney injury (AKI). This inference is drawn primarily from trials of its use in patients with ARDS and after cardiac surgery. 

An interesting paradox is the finding that short-term use (24 hours post-surgery) of iNO in patients who require prolonged cardiopulmonary bypass may have a protective effect for AKI. This short-term benefit is due to the fact that, in prolonged bypass cases, increased hemolysis raises plasma levels of free oxyhemoglobin, which binds and depletes endogenous NO, leading to vasoconstriction, impaired tissue perfusion, and inflammation (reference #3).

#cardiovascular

#nephrology

References:

1. Ruan SY, Huang TM, Wu HY, et al. Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials. Crit Care 2015; 19:137.

2. Gebistorf F, Karam O, Wetterslev J, Afshari A. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev 2016; :CD002787.

3. Lei C, Berra L, Rezoagli E, et al. Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery. Am J Respir Crit Care Med 2018; 198:1279.

The time-relationship of 'osmolal gap' and 'Anion gap' in toxic alcohols

Q: In Methanol and Ethylene Glycol toxicity, the time-relationship of 'osmolal gap' and 'Anion gap' is inversely proportional.

A) True

B) False

Answer: A

After ingestion of Methanol and Ethylene Glycol, the osmolal gap continues to drop as the alcohols are metabolized, while the anion gap rises. The following graph best describes the relationship.

#toxicity

References:

1. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med. 2018 Jan 18;378(3):270-280. doi: 10.1056/NEJMra1615295. Erratum in: N Engl J Med. 2019 Jan 10;380(2):202. doi: 10.1056/NEJMx180046. PMID: 29342392.

2. Gallagher N, Edwards FJ. The Diagnosis and Management of Toxic Alcohol Poisoning in the Emergency Department: A Review Article. Adv J Emerg Med. 2019 May 22;3(3):e28. doi: 10.22114/ajem.v0i0.153. PMID: 31410405; PMCID: PMC6683589.

Clinical features of infective endocarditis

Q: A 52-year-old male with a history of End Stage Renal Disease (ESRD) is admitted to the ICU with suspected infective endocarditis (IE). On clinical exam found to have Janeway lesions. Janeway lesions are more common in? - select one

A) acute IE

B) subacute IE

Answer: A

Clinical exam in IE plays an important role. Three hallmark characteristic findings, though relatively uncommon, are highly suggestive of IE:

• Janeway lesions
• Osler nodes 
• Roth spots 

Janeway lesions are nontender erythematous macules on the palms and soles. Histologically, they are microabscesses with neutrophil infiltration of capillaries. Janeway lesions are more common in acute than subacute IE. 

In contrast, Osler nodes and Roth spots occur over a protracted time course of endocarditis. These two entities are sequelae of microthromboembolic occlusion, leading to localized immune-mediated vasculitis. Osler nodes, in contrast to Janeway lesions, are tender and subcutaneous (SQ) violaceous nodules mostly on the pads of the fingers and toes, and may also occur on the thenar and hypothenar eminences. Interestingly, tenderness begins a few days before the nodule appears. Roth spots are exudative, edematous, hemorrhagic lesions of the retina with pale centers.

#physical-exam

#ID

References:

1. Saccente M, Cobbs CG. Clinical approach to infective endocarditis. Cardiol Clin. 1996 Aug;14(3):351-62. doi: 10.1016/s0733-8651(05)70289-7. PMID: 8853130.

2. Loughrey PB, Armstrong D, Lockhart CJ. Classical eye signs in bacterial endocarditis. QJM 2015; 108:909.

3. Abdelgawad H, Azab S, Abdel-Hay MA, Almaghraby A. Clinical features and outcomes of infective endocarditis: a single-centre experience. Cardiovasc J Afr. 2023 May-Jun 23;34(2):82-88. doi: 10.5830/CVJA-2022-027. Epub 2022 Aug 3. PMID: 35924572; PMCID: PMC10512034.

extraocular muscles in CIM

Q: In Critical Illness Myopathy (CIM), the presence of extraocular muscle weakness is diagnostic.

A) True

B) False

Answer: B

CIM has a few characteristic features:

• Flaccid quadriparesis 
• Proximal muscles are affected more than distal muscles.
• Ventilatory failure
• Facial muscle weakness (may or may not present)
• Sparing of extraocular muscles (very rarely involved)
• Intact sensation*
• Intact deep tendon reflexes*

*feature of Critical Illness Polyneuropathy (CIP)

References:

1. Latronico N, Rasulo FA, Eikermann M, Piva S. Illness Weakness, Polyneuropathy and Myopathy: Diagnosis, treatment, and long-term outcomes. Crit Care. 2023 Nov 13;27(1):439. doi: 10.1186/s13054-023-04676-3. Erratum in: Crit Care. 2023 Nov 30;27(1):469. doi: 10.1186/s13054-023-04757-3. PMID: 37957759; PMCID: PMC10644573.

2. Hermans G, Van den Berghe G. Clinical review: intensive care unit acquired weakness. Crit Care. 2015 Aug 5;19(1):274. doi: 10.1186/s13054-015-0993-7. PMID: 26242743; PMCID: PMC4526175.

aortopulmonary angle

Q: On chest X-ray, the aortopulmonary angle can be found on? - select one

A) left side

B) right side

Answer: A

The aortopulmonary angle, also called the aortopulmonary space or window, is a space between the aortic arch and the left pulmonary artery. It contains the ligamentum arteriosum, the left recurrent laryngeal nerve, lymph nodes, and fatty tissue. The space is bounded anteriorly by the ascending aorta, posteriorly by the descending aorta, medially by the left main bronchus, and laterally by the mediastinal pleura.

Clinical Significance: The presence of water radiodensity in this space on radiography may indicate a lymphadenopathy or possible neoplasm.

#pulmonary

#radiology

References:

1. Dewey, Marc; Magid, Donna; Wheeler, Paul S.; Hamm, Bernd (2004). "Aortopulmonary Window or Angle on the Chest Radiograph?". American Journal of Roentgenology. 182 (4): 1085–1086. doi:10.2214/ajr.182.4.1821085. ISSN 0361-803X. PMID 15039195.

2. Heitzman E, Lane E, Hammack D, Rimmler L (1975). "Radiological evaluation of the aortic-pulmonic window". Radiology. 116 (3): 513–8. doi:10.1148/116.3.513. PMID 1153753.

Enteral free water in high ICP

Q: Patients with elevated Intra-Cranial Pressure (ICP) should not be fed enteral free water.

 A) True

B) False

 Answer: A 

Patients with elevated ICP should be kept euvolemic, rather normo- to hyperosmolar. Any hypotonic fluid administration, including enteral free water, should be avoided whenever possible. Isotonic fluids are usually utilized guided by close monitoring of labs. Serum osmolality is targeted to stay above 280 mOsm/L, between 295 and 305 mOsm/L. Colloids have no specific advantage. 

 Clinicians should be aware that hyponatremia is common in patients with elevated ICP, particularly in patients with subarachnoid hemorrhage SAH). Hypertonic saline in bolus, popularly known as 'salt bomb' can be used per clinical judgement.

 #neurology 

 References: 

 1. Schmoker JD, Shackford SR, Wald SL, Pietropaoli JA. An analysis of the relationship between fluid and sodium administration and intracranial pressure after head injury. J Trauma 1992; 33:476. 

 2. Tranmer BI, Iacobacci RI, Kindt GW. Effects of crystalloid and colloid infusions on intracranial pressure and computerized electroencephalographic data in dogs with vasogenic brain edema. Neurosurgery 1989; 25:173.

 3. SAFE Study Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group, Australian Red Cross Blood Service, et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007; 357:874.

SCC

Q: Small cell carcinoma in the lungs is considered a neuroendocrine tumor.

A) True

B) False

Answer: A

Small cell carcinoma, large cell neuroendocrine carcinoma, typical carcinoid, and atypical carcinoid all fall under the category of neuroendocrine tumors and share features with carcinoid lesions arising at other body sites. 

Small cell carcinomas and large cell neuroendocrine carcinomas have aggressive courses and, pathologically, exhibit a higher mitotic rate, distinguishing them from pulmonary carcinoids.

#oncology

#pulmonary

References:

1. WHO Classification of Tumours Editorial Board. Thoracic Tumours. In: WHO Classification of Tumours, 5th ed, IARC Publications, 2021. Vol 5.

2. Orlandi R. Neuroendocrine neoplasms of the lung: The latest updates. World J Clin Oncol. 2025 May 24;16(5):106630. doi: 10.5306/wjco.v16.i5.106630. PMID: 40503410; PMCID: PMC12149839.

3. Rekhtman N. Lung neuroendocrine neoplasms: recent progress and persistent challenges. Mod Pathol. 2022 Jan;35(Suppl 1):36-50. doi: 10.1038/s41379-021-00943-2. Epub 2021 Oct 18. PMID: 34663914; PMCID: PMC8695375.

Midazolam as intranasal or buccal route

Q: What is the dose of Midazolam to give intranasally if no IV or IM route is available?

Answer: if its an emergency and no IV line is established or (let say) if no syringe is available even to give intramuscularly (IM), midazolam can be given intranasally using the injectable solution of 5 mg/mL as a metered spray of 0.1 mL containing 0.5 mg, three to five times per nostril, and can be repeated, to a total dose of 10 mg for adults.

It can also be given buccally as 0.2 mg/kg, or a total of 10 mg altogether, once in adults.

#neurology

#pharmacology

References:

1. McKee HR, Abou-Khalil B. Outpatient pharmacotherapy and modes of administration for acute repetitive and prolonged seizures. CNS Drugs 2015; 29:55.

2. Dittrich TD, Vock D, Fisch U, et al. Efficacy and Tolerability of Intranasal Midazolam Administration for Antiseizure Treatment in Adults: A Systematic Review. Neurocrit Care 2024; 41:632.

3. Kay L, Merkel N, von Blomberg A, Willems LM, Bauer S, Reif PS, Schubert-Bast S, Rosenow F, Strzelczyk A. Intranasal midazolam as first-line inhospital treatment for status epilepticus: a pharmaco-EEG cohort study. Ann Clin Transl Neurol. 2019 Dec;6(12):2413-2425. doi: 10.1002/acn3.50932. Epub 2019 Nov 4. PMID: 31682078; PMCID: PMC6917318.

4. Armijo JA, Herranz JL, Pena Pardo MA, Adín J. Midazolam intranasal y bucal en el tratamiento de las convulsiones agudas [Intranasal and buccal midazolam in the treatment of acute seizures]. Rev Neurol. 2004 Mar 1-15;38(5):458-68. Spanish. PMID: 15029526.

CIM

Q: The Critical Illness Myopathy (CIM) affects which group of muscles more? - select one

A) distal 

B) proximal 

Answer: B

CIM, although it causes flaccid quadriparesis, usually affects the proximal muscles more. It is also associated with facial muscle weakness.

A pure exclusive CIM can be distinguished from Critical Illness Polyneuropathy (CIP) by normal sensation and normal or attenuated deep tendon reflexes. Patients with exclusive CIM grimace to pain even when they are encephalopathic.

Unfortunately, most patients suffer from combined CIP and CIM.

#ICU-course

#neurology

References:

1. Lacomis D, Giuliani MJ, Van Cott A, Kramer DJ. Acute myopathy of intensive care: clinical, electromyographic, and pathological aspects. Ann Neurol 1996; 40:645.

2. Z'Graggen WJ, Tankisi H. Critical Illness Myopathy. J Clin Neurophysiol. 2020 May;37(3):200-204. doi: 10.1097/WNP.0000000000000652. PMID: 32358245.

3. Rodriguez B, Larsson L, Z'Graggen WJ. Critical Illness Myopathy: Diagnostic Approach and Resulting Therapeutic Implications. Curr Treat Options Neurol. 2022;24(4):173-182. doi: 10.1007/s11940-022-00714-7. Epub 2022 Mar 28. PMID: 35370393; PMCID: PMC8958813.

4. Friedrich O. Critical illness myopathy: what is happening? Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):403-9. doi: 10.1097/01.mco.0000232900.59168.a0. PMID: 16778569.

banana bag

Q: Utilizing "Banana bag" plays an integral part in the management of alcohol withdrawal as it contains thiamine.

A) True

B) False

Answer: B

Although in the United States, use of "banana bag" is almost an integral part of management in alcohol withdrawal, there is no evidence that it prevents or contributes much to preventing Wernicke's encephalopathy or Delirium Tremens (DTs). It is called a banana bag due to its yellow color and contains

• thiamine
• folate
• multivitamin (MVI)
• isotonic saline with 5% dextrose

It is true that thiamine (given first) and glucose should be administered to prevent or treat Wernicke encephalopathy in the early phase of management, but preparing or specifically requesting a banana bag is not supported by evidence! 

Electrolytes, vitamins, and volume should be administered as needed per clinical and laboratory values.

#toxicity

References:

1. Flannery AH, Adkins DA, Cook AM. Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU. Crit Care Med. 2016 Aug;44(8):1545-52. doi: 10.1097/CCM.0000000000001659. PMID: 27002274.

2. LoVecchio F. Multivitamin "banana bags" provide little value in emergency department patients. Ann Emerg Med. 2012 May;59(5):414-5. doi: 10.1016/j.annemergmed.2011.11.007. PMID: 22525531.

3. Wells C, Butcher R, McCormack S. Intravenous Multivitamin Therapy Use in Hospital or Outpatient Settings: A Review of Clinical Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 Oct 15. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567072/

Kt/V

Q: What is the target Kt/V in patients with peritoneal dialysis? - select one

A) ≥ 1.3/week

B) ≥ 1.7/week

Answer: B

The objective of this question is to introduce students to the concept of Kt/V in dialysis patients, which is used to indicate dialysis adequacy. The K, t, and V stand respectively for:

K – dialyzer clearance of urea

t – dialysis time

V – volume of distribution of urea*

Per the US National Kidney Foundation, in hemodialysis (HD), the target is ≥1.3^, and in peritoneal dialysis, the target is ≥1.7/week. Although there are various criticisms against its use, it remains a vital concept for clinicians to know.

Clinical significance: It correlates with survival.

There are online calculators available to determine Kt/V

*approximately equal to the patient's total body water

^ Per Centers for Medicare and Medicaid Services (CMS): the minimum required is ≥1.2 per session

References/further reading:

1. Churchill BM, Patri P. The Nitty-Gritties of Kt/Vurea Calculations in Hemodialysis and Peritoneal Dialysis. Indian J Nephrol. 2021 Mar-Apr;31(2):97-110. doi: 10.4103/ijn.IJN_245_19. Epub 2021 Apr 2. PMID: 34267430; PMCID: PMC8240937.

2. Gotch FA. Kt/V is the best dialysis dose parameter. Blood Purif. 2000;18(4):276-85. doi: 10.1159/000014449. PMID: 10965068.

3. Maliha G, Weinhandl ED, Reddy YNV. Deprescribing the Kt/V Target for Peritoneal Dialysis in the United States: The Path Toward Adopting International Standards for Dialysis Adequacy. J Am Soc Nephrol. 2023 May 1;34(5):751-754. doi: 10.1681/ASN.0000000000000101. Epub 2023 Feb 14. PMID: 36787755; PMCID: PMC10125636.