CF and Na

 Q; 24 years old male with a history of Cystic Fibrosis (CF) is admitted to ICU with severe dehydration after a long day outdoors in the summer. All of the following abnormalities are expected EXCEPT?

A) hypernatremia 

B) hypochloremia 

C) hypokalemia 

D) metabolic alkalosis

Answer: A 

Though unusual, electrolyte abnormalities can be presenting symptoms in patients with CF. This is popularly known as pseudo-Bartter syndrome. This condition occurs due to excessive loss of NaCl during sweating, compounded by decrease sodium intake.

#electrolyte imbalance

References:

1. Vilotijević-Dautović G, Stojanović V. Pseudo-Bartter's Syndrome in Patients with Cystic Fibrosis: A Case Series and Review of the Literature. Srp Arh Celok Lek. 2015 Nov-Dec;143(11-12):748-51. doi: 10.2298/sarh1512748v. PMID: 26946774. 

2. Scurati-Manzoni E, Fossali EF, Agostoni C, et al. Electrolyte abnormalities in cystic fibrosis: systematic review of the literature. Pediatr Nephrol 2014; 29:1015. 

3. Ghimire S, Yerneni H, Oyadomari TA, Sedlacek M. Metabolic Alkalosis and Cystic Fibrosis: A Case Report. Ann Intern Med 2020; 173:315. 

4. Dahabreh MM, Najada AS. Pseudo-bartter syndrome, pattern and correlation with other cystic fibrosis features. Saudi J Kidney Dis Transpl. 2013 Mar;24(2):292-6. doi: 10.4103/1319-2442.109579. PMID: 23538352.

PSGN

 Q: 67 years old school principal is transferred from a rural community hospital with the diagnosis of poststreptococcal glomerular nephritis (PSGN). Patient on arrival to ICU was found to be hypertensive. Chest X-ray showed pulmonary edema. An immediate renal biopsy followed by dialysis is required? 

A) Yes 

B) No 

 

Answer: B 

 PSGN is common in children and adults over the age of 60. Treatment is supportive and dialysis is rarely required if severe acidosis, electrolyte imbalance, and massive volume overload stays refractory to medical management. Although, obese and diabetic patients are more prone to go in renal failure.

Initial treatment includes diuresis with loop diuretics, blood pressure control, and water and sodium restrictions. Penicillin-based antibiotics or erythromycin are usually added, although their specific efficacy in PSGN is not certain.

#nephrology

#ID

References:

1. Rawla P, Padala SA, Ludhwani D. Poststreptococcal Glomerulonephritis. [Updated 2021 Mar 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538255/ 

2. Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol 2008; 19:1855.

Angina and position

 Q: Angina pectoris tends to get worse with lying down?

A) True

B) False

Answer: A

There is conventional teaching that angina is constant pain or discomfort which does not change with change in breathing or position. In actuality, angina may get worse with lying down. In the supine position, there is an increase in venous return causing an increase in myocardial wall stress.

Other factors to worsen angina include increase physical activity, cold, emotional trauma, sexual intercourse, large meals, use of cocaine or other recreational drugs.

#cardiology

References:

Kloner RA, Chaitman B. Angina and Its Management. J Cardiovasc Pharmacol Ther. 2017 May;22(3):199-209. doi: 10.1177/1074248416679733. Epub 2016 Dec 14. PMID: 28196437. 

 Constant J. The diagnosis of nonanginal chest pain. Keio J Med. 1990 Sep;39(3):187-92. doi: 10.2302/kjm.39.187. PMID: 2255129.

HIVAN

Q: Hypertensive emergency is one of the classic symptoms of patients with HIV-associated nephropathy (HIVAN)?

 
A) True 

B) False 

Answer: B

In contrast to other patients with chronic kidney diseases, hypertension (HTN) is a rare presentation in HIVAN. It is present in only 12-25 percent of patients with HIVAN. Edema is also less likely in comparison to other patients with severe proteinuria and decreased estimated glomerular filtration rate (eGFR). This is an interesting paradox as patients with HIVAN are subject to nephrotic-range proteinuria on presentation. This is due to the fact that microalbuminuria usually goes undiagnosed in these patients earlier in the disease. 

Another unusual presentation of HIVAN is possible hematuria.

#nephrology

#HIV

References:

1. Medapalli RK, He JC, Klotman PE. HIV-associated nephropathy: pathogenesis. Curr Opin Nephrol Hypertens. 2011;20(3):306-311. doi:10.1097/MNH.0b013e328345359a

2. Lescure FX, Flateau C, Pacanowski J, et al. HIV-associated kidney glomerular diseases: changes with time and HAART. Nephrol Dial Transplant 2012; 27:2349. 

3. Bigé N, Lanternier F, Viard JP, et al. Presentation of HIV-associated nephropathy and outcome in HAART-treated patients. Nephrol Dial Transplant 2012; 27:1114.

Tramadol and serotonin toxicity

 Q: Tramadol is an opiod?

A) True

B) False

Answer: A

Tramadol is increasingly becoming a part of multi-model analgesia protocols, particularly in post-surgical ICU patients. Tramadol is called a mixed mechanism opioid because it has weak affinity for mu-opioid receptors. It is also serotonin and norepinephrine reuptake inhibitor. 

The objective of this question is to highlight the risk of serotonin syndrome due to wide use of serotonin reuptake inhibitors in the population. A combination of tramadol and serotonin reuptake inhibitors may cause life-threatening serotonin toxicity and seizures.

#toxicology

#pharmacology

References:

1. Nelson EM, Philbrick AM. Avoiding serotonin syndrome: the nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Ann Pharmacother. 2012 Dec;46(12):1712-6. doi: 10.1345/aph.1Q748. Epub 2012 Dec 4. PMID: 23212934.

2. Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015 Jul-Aug;18(4):395-400. PMID: 26218943. 

3. Hassamal S, Miotto K, Dale W, Danovitch I. Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures. Am J Med. 2018 Nov;131(11):1382.e1-1382.e6. doi: 10.1016/j.amjmed.2018.04.025. Epub 2018 May 10. PMID: 29752906.

Midodrine in cirrhosis

 Q: 54 years old male with a history of cirrhosis is admitted to ICU with massive ascites, hypotension, and advanced hepato-renal syndrome. Patient requires large-volume paracentesis (LVP). Patient is allergic to albumin. Which drug can be used as an alternative to albumin in LVP?

Answer: Midodrine 

Midodrine is considered an oral vasopressor that has many advantages in advanced-stage cirrhotic patients. In hospitalized patients, it has been found as an alternative or an adjuvant treatment with albumin/colloid infusion who require large-volume paracentesis (LVP). 

Midodrine also has many other advantages in these patients. Being a vasopressor it increases blood pressure, improves renal perfusion, increases renal sodium excretion, reduces ascites, and is found to improve survival. 

In combination with octreotide, it may reverse type I hepatorenal syndrome.

#hepatology

#pharmacology

References:

1. Singh V, Dheerendra PC, Singh B, et al. Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: a randomized pilot study. Am J Gastroenterol 2008; 103:1399.

2. Singh V, Dhungana SP, Singh B, et al. Midodrine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study. J Hepatol 2012; 56:348. 

3. Singh V, Singh A, Singh B, et al. Midodrine and clonidine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study. Am J Gastroenterol 2013; 108:560.

Ramsay Hunt Syndrome

 Q: Which of the following is NOT a part of the triad in Ramsay Hunt syndrome? 

A) ipsilateral facial paralysis 

B) ear pain 

C) vesicles in auditory canal or auricle 

D) vertigo

Answer: D

Ramsay Hunt syndrome is actually an otologic manifestation of Herpes. Its proper scientific name is herpes zoster oticus with facial palsy. It is famous for its triad of 

• ipsilateral facial paralysis 
• ear pain, and 
• vesicles in the auditory canal or on the auricle 

There can be many other symptoms of this syndrome that are not part of the triad but are frequently encountered. These include ipsilateral altered taste perception, ipsilateral tongue lesions, decreased or increased (hyperacusis) hearing, tinnitus, lacrimation and vertigo. 

Ramsay Hunt syndrome occurs due to herpes reactivation of latent Varicella Zoster Virus (VZV) in the geniculate ganglion, with spread of infection to the 8th cranial nerve. It has also been described as a part of multiple cranial nerves VZV. 

Another objective of this question is to highlight its worse symptomatic presentation and outcome when compared to Bell's palsy. It has fewer chances of recovery.

#ID

#ENT

References:

1. Kuhweide R, Van de Steene V, Vlaminck S, Casselman JW. Ramsay Hunt syndrome: pathophysiology of cochleovestibular symptoms. J Laryngol Otol. 2002 Oct;116(10):844-8. doi: 10.1258/00222150260293691. PMID: 12437843. 

2. Ryu EW, Lee HY, Lee SY, Park MS, Yeo SG. Clinical manifestations and prognosis of patients with Ramsay Hunt syndrome. Am J Otolaryngol. 2012 May-Jun;33(3):313-8. doi: 10.1016/j.amjoto.2011.10.001. Epub 2011 Nov 8. PMID: 22071033. 

3. Jeon Y, Lee H. Ramsay Hunt syndrome. J Dent Anesth Pain Med. 2018;18(6):333-337. doi:10.17245/jdapm.2018.18.6.333 

4. Lee DH, Chae SY, Park YS, Yeo SW. Prognostic value of electroneurography in Bell's palsy and Ramsay-Hunt's syndrome. Clin Otolaryngol 2006; 31:144. 

5. Uscategui T, Dorée C, Chamberlain IJ, Burton MJ. Antiviral therapy for Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev 2008; :CD006851.

BP and stroke in preeclampsia/eclampsia

 Q: Which of the following is more predictive of adverse neurological events in patients with preeclampsia/eclampsia? (select one)

A) Systolic Blood Pressure (SBP)

B) Diastolic Blood Pressure (DBP)

C) Mean Arterial Pressure (MAP)

Answer: A

An important study published in 2019 from California comprising of 54 preeclampsia pregnancy-related deaths recorded over 5 years, showed 33 attributed to strokes - where SBP was above 160 mm Hg in 96% of cases. DBP was 110 or higher in 65% of cases. 

Headache was reported by 87% of women before the stroke. The objective of this question is to point out this clinical warning/sign as a "good-to-strong chance to alter outcome" in two-thirds of cases with prompt blood pressure control.

#ob-gyn

#cardiology

#neurology

Reference:

Judy AE, McCain CL, Lawton ES, et al. Systolic Hypertension, Preeclampsia-Related Mortality, and Stroke in California. Obstet Gynecol 2019.

TIC

Q: Trauma-induced coagulopathy (TIC) is due to 

A) acidosis 

B) hypothermia 

C) hemodilution 

D) none of the above

Answer: D

There are multiple etiologies for coagulopathy in trauma patients like acidosis, hypothermia, or hemodilution. Besides this 'vicious triad' (choices A, B, and C) trauma itself and  'independently' can lead to coagulopathy, and is called Trauma-Induced Coagulopathy (TIC). 

 

This is multifactorial and due to a direct biochemical response to tissue injury and shock. Mechanisms include dysregulated coagulation, altered fibrinolysis, systemic endothelial dysfunction, inflammatory responses to injury, and platelet dysfunction.

#trauma

#hematology

References:

1. Moore HB, Gando S, Iba T, et al. Defining trauma-induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH. J Thromb Haemost 2020; 18:740. 

2. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003; 54:1127. 

3. Chang R, Cardenas JC, Wade CE, Holcomb JB. Advances in the understanding of trauma-induced coagulopathy. Blood 2016; 128:1043. 

4. Hess JR, Brohi K, Dutton RP, et al. The coagulopathy of trauma: a review of mechanisms. J Trauma 2008; 65:748.

DDAVP and sodium

 Q:  Desmopressin (DDAVP) tends to cause? (select one)

A) hyponatremia

B) hypernatremia

Answer: A

Desmopressin is actually a 1-deamino-8-D-arginine vasopressin, popularly known as DDAVP. As the name implies it is an analog of antidiuretic hormone and tends to decrease urine output. Consequently, it also causes hyponatremia besides some vasopressor activity. DDAVP is frequently given in ICU to bleeding patients. It improves the bleeding time by increasing the release of large factor VIII:von Willebrand factor multimers from endothelial cells. It is also postulated to increase platelet membrane glycoprotein expression. 

It should be noted that it quickly develops tachyphylaxis (usually after the second dose). The dose is 0.3 mcg/kg. It should be given slowly in an IV piggy bag for over half an hour period.

#hematology

#pharmacology

References:

1. Vande Walle J, Stockner M, Raes A, Nørgaard JP. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf. 2007 Sep;2(3):232-8. doi: 10.2174/157488607781668891. PMID: 18690973. 

2. Fralick M, Schneeweiss S, Wallis CJD, Jung EH, Kesselheim AS. Desmopressin and the risk of hyponatremia: A population-based cohort study. PLoS Med. 2019 Oct 21;16(10):e1002930. doi: 10.1371/journal.pmed.1002930. PMID: 31634354; PMCID: PMC6802819. 

3. Zeigler ZR, Megaludis A, Fraley DS. Desmopressin (d-DAVP) effects on platelet rheology and von Willebrand factor activities in uremia. Am J Hematol 1992; 39:90. 

4. Gordz S, Mrowietz C, Pindur G, et al. Effect of desmopressin (DDAVP) on platelet membrane glycoprotein expression in patients with von Willebrand's disease. Clin Hemorheol Microcirc 2005; 32:83.

Amiodarone and sildenafil

 Q: Amiodarone ____________ the efficacy of sildenafil? (select one) 

A) increases 

B) decreases

Answer: A

Sildenafil has been increasingly used in ICU for pulmonary hypertension. Simultaneously these patients are prone to arrhythmia particularly atrial fibrillation, requiring amiodarone for rapid ventricular rate (RVR) control. 

Amiodarone interacts with many drugs commonly used in ICU and as a rule of thumb increases the efficacy, and subsequently the potential of their side effects. Some of these drugs include digoxin, warfarin, simvastatin, sildenafil, cyclosporine, and many hepatically metabolized drugs such as antidepressants.

#pharmacology

#cardiology

#pulmonary

References:

1. Colunga Biancatelli RM, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of Amiodarone. J Geriatr Cardiol. 2019;16(7):552-566. doi:10.11909/j.issn.1671-5411.2019.07.004

2. Florek JB, Girzadas D. Amiodarone. 2020 Aug 23. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 29489285.

3. McDonald MG, Au NT, Rettie AE. P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of Inhibitory Mechanisms. Drug Metab Dispos. 2015 Nov;43(11):1661-9. doi: 10.1124/dmd.115.065623. Epub 2015 Aug 21. PMID: 26296708; PMCID: PMC4613947.

tranexamic acid with acute gastrointestinal bleeding

 Q: Tranexamic acid can be used as an adjuvant treatment in patients with severe upper Gastrointestinal bleed (GIB)?

A) Yes

B) No

Answer: B

Tranexamic acid has been suggested as an adjuvant treatment in severe upper GIB due to its antifibrinolytic properties. After few initial studies showed some evidence of improvement in mortality,  a subsequent large RCT with 12,000 patients failed to show any benefit. Moreover, it carries a higher risk to cause deep vein thrombosis (DVT), pulmonary embolism (PE), and seizures.

#GI

References:

1. Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2014; :CD006640. 

2. HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet 2020; 395:1927.

diagnostic criteria for Parkinson Disease

 Q: 62 years old male is recovering in ICU with pneumonia. A physical therapist is worried about patient having underlying Parkinson's Disease (PD) due to difficulty in mobilization. Which of the following is NOT considered as a diagnostic criterion for Parkinson's Disease? 

A) tremor

B) bradykinesia

C) rigidity

D) postural instability

Answer: D

The three classics and cardinal features of PD are 

• tremor 
• bradykinesia, and 
• rigidity 

 Postural instability is relatively a late presentation and is not considered a part of diagnostic criteria. Said that severity of postural instability has two clinical implications. It is minimally responsive to dopaminergic therapy and is an independent predictor of mortality for PD.  

#neurology

#geriatrics

References:

1. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol 1999; 56:33. 

2. Forsaa EB, Larsen JP, Wentzel-Larsen T, Alves G. What predicts mortality in Parkinson disease?: a prospective population-based long-term study. Neurology 2010; 75:1270. 

3. Koller WC, Glatt S, Vetere-Overfield B, Hassanein R. Falls and Parkinson's disease. Clin Neuropharmacol 1989; 12:98.

Lyme carditis

 Q: 44 years old male who was diagnosed with Lyme's disease 4 weeks ago, is now admitted to ICU with syncope and Atrio-ventricular block (AV-block) on EKG. It would be prudent to insert a permanent pacemaker to avoid sudden cardiac death?

A) True

B) False

Answer: B

AV block due to Lyme carditis is usually short-lived and resolved by six weeks. A temporary pacemaker may be required but a permanent pacemaker is rarely needed. While evaluating the EKG on a patient suspected to have Lyme carditis, it is important to pay attention to the PR interval. If the PR interval is more than 300 milliseconds, there is a high chance of the patient progressing to complete AV block, which may require a temporary pacemaker. 

Patients who fail to complete the antibiotic course appropriately for any early signs of Lyme disease-like erythema migrans are more prone to progress to Lyme carditis.

#cardiology

References:

1. Steere AC, Batsford WP, Weinberg M, et al. Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 1980; 93:8. 

2. Yeung C, Baranchuk A. Diagnosis and Treatment of Lyme Carditis: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Feb 19;73(6):717-726. doi: 10.1016/j.jacc.2018.11.035. Erratum in: J Am Coll Cardiol. 2019 Nov 26;74(21):2709-2711. PMID: 30765038. 

3. Sangha O, Phillips CB, Fleischmann KE, et al. Lack of cardiac manifestations among patients with previously treated Lyme disease. Ann Intern Med 1998; 128:346. 

4. van der Linde MR, Crijns HJ, Lie KI. Transient complete AV block in Lyme disease. Electrophysiologic observations. Chest 1989; 96:219.

Neostigmine in acute colonic pseudo obstruction

 Q: What are the few options to decrease the side effects of Neostigmine when used to relieve acute colonic pseudo-obstruction, popularly known as Ogilvie's syndrome? 

 Answer: Neostigmine is an acetylcholinesterase inhibitor and is very effective in patients with acute colonic pseudo-obstruction, especially patients who fail conservative measures for 2-3 days or have cecal diameter > 12 cm. Some of the side effects are bradycardia going towards asystole (atropine is recommended to be available at the bedside), seizures, restlessness, tremor, salivation, sweating, bronchoconstriction, abdominal cramps, nausea, and vomiting. Few strategies to minimize the side effects are 

• Inject slowly over 5 minutes
• Keep patient supine (with bedpan to decrease the nuisance of stool passage)
• Decrease the dose to 1.5 mg or even to 0.5-1 mg in high-risk patients 
• Co-administration of glycopyrrolate which is an anticholinergic agent with minimal effect on the muscarinic receptors of the colon

#GI

References:

1. Naveed M, Jamil LH, Fujii-Lau LL, et al. American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the management of acute colonic pseudo-obstruction and colonic volvulus. Gastrointest Endosc 2020; 91:228. 

2. Saunders MD, Kimmey MB. Systematic review: acute colonic pseudo-obstruction. Aliment Pharmacol Ther 2005; 22:917. 

3. Kram B, Greenland M, Grant M, et al. Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo-obstruction, or Refractory Constipation. Ann Pharmacother 2018; 52:505. 

4.  Korsten MA, Rosman AS, Ng A, et al. Infusion of neostigmine-glycopyrrolate for bowel evacuation in persons with spinal cord injury. Am J Gastroenterol 2005; 100:1560.

IVF and K

 Q: Patients with hyperkalemia should be given saline as intravenous fluid (IVF)? (select one)

A) with D-5 

B) without D-5

Answer: A

Usually, IVF resuscitation is sufficient with normal saline. But in patients with potassium level trending towards higher side (hyperkalemia) adding dextrose with saline may help. Dextrose stimulates the insulin release. It increases the entry of potassium into the cell and helps to lower serum hyperkalemia.

#resuscitation

#electrolytes

#endocrine

Reference:

1. Chin KJ, Macachor J, Ong KC, Ong BC. A comparison of 5% dextrose in 0.9% normal saline versus non-dextrose-containing crystalloids as the initial intravenous replacement fluid in elective surgery. Anaesth Intensive Care. 2006 Oct;34(5):613-7. doi: 10.1177/0310057X0603400511. PMID: 17061636. 

2. Ricciuti A, Milani GP, Tarantino S, et al. Maintenance Fluid Therapy with Saline, Dextrose-Supplemented Saline or Lactated Ringer in Childhood: Short-Term Metabolic Effects. Nutrients. 2020;12(5):1449. Published 2020 May 17. doi:10.3390/nu12051449

PEG tube dislodgement

Q: 74 years old patient with recent CVA is status post percutaneous endoscopic gastrostomy (PEG) tube placement one week ago. Patient became delirious and pulled his PEG tube. Intensivist was called at the bed side within 5 minutes. PEG tube can be safely put back through the stoma while it is patent? 

 A) Yes 

 B) No

Answer: B

For safety and protection, most PEG tubes are designed in a way that they can sustain about 10-14 pounds of external pull pressure. Said that it is a common scenario in hospitalized patients to have PEG tube dislodged accidentally. PEG tract usually matured by week 4. Prior to that it is not a good idea to blindly re-insert the PEG tube through immature gastric tract. 

This is due to the fact that the gastric wall and the abdominal wall may have separated, and blindly inserted PEG tube may end up in peritoneal cavity. GI or surgical service should be called back. Alternatively, a contrast study should be performed to confirm the proper position of the reinserted tube. 

If the tract is matured, there should not be a delay to insert replacement tube (or keep it patent with any tube such as Foley catheter). Mature tract may close within few hours.

#procedures

References:

1. Cmorej P, Mayuiers M, Sugawa C. Management of early PEG tube dislodgement: simultaneous endoscopic closure of gastric wall defect and PEG replacement. BMJ Case Rep. 2019 Sep 4;12(9):e230728. doi: 10.1136/bcr-2019-230728. PMID: 31488448; PMCID: PMC6731818.

2. Shah R, Shah M, Aleem A. Gastrostomy Tube Replacement. [Updated 2021 May 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482422/

storage lesion

 Q; Prolonged storage of packed red blood cell may cause all of the following EXCEPT? (select one) 

A) increased pH 

B) chelation of calcium 

C) low 2,3-diphosphoglycerate (DPG) levels 

D) decreased clotting factor concentration

Answer: A

It has been suggested that one of the reasons for resuscitation associated coagulopathy is the prolonged storage of packed red blood cell (pRBC) in blood bank. The term "storage lesion" has been coined for this phenomenon. The components of storage lesion includes decreased pH, chelation of calcium, low 2,3-DPG levels, and decreased clotting factor concentration. 

Studies have shown that despite these changes there is no difference in outcome between fresh pRBCs and stored pRBCs transfusions. 

The objective of this pearl is to discourage clinicians from writing orders for "only fresh pRBC units". This can have high undesirable challenges on blood supplies.

#hematology

References:

1. Green RS, Erdogan M, Lacroix J, et al. Age of transfused blood in critically ill adult trauma patients: a prespecified nested analysis of the Age of Blood Evaluation randomized trial. Transfusion 2018; 58:1846. 

2.  Steiner ME, Ness PM, Assmann SF, et al. Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med 2015; 372:1419. 

3. Heddle NM, Cook RJ, Arnold DM, et al. Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion. N Engl J Med 2016; 375:1937. 

4. Lacroix J, Hébert PC, Fergusson DA, et al. Age of transfused blood in critically ill adults. N Engl J Med 2015; 372:1410.

Mucoactive agents for acute respiratory failure

 Q: Mucolytics should be used in all acute respiratory failure patients requiring ventilator?

A) True

B) False

Answer: B

A recent metanalysis consisting of 13 randomized controlled trials (RCTs) consisting of 1712 patients failed to show any benefit of mucolytics in ARDS and acute respiratory failure patients who require ventilator. Four different mucoactive agents were investigated in these RCTs. 

There was a slight favor towards decrease ICU stay, otherwise there was no effect on ventilator days, ventilator-free days, hospital stay or mortality. 

#ventilators

#pulmonary

Reference:

Anand R, McAuley DF, Blackwood B, et al. Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis. Thorax 2020; 75:623.

feeding tube and decompression

 Q: If a dobhoff feeding tube is already in place, it can be used to decompress the stomach?

A) Yes

B) No

Answer: B

Feeding tubes are designed in a way that they have soft walls and collapse while suction is applied for decompression. A nasogastric tube (NGT) is a proper tube to decompress the stomach. Gastric decompression though sound simple has major implications besides control of vomiting, distension, and aspiration especially in post-operative abdominal surgical patients. It provides better healing of intestinal suture lines, prevents wound dehiscence and evisceration. It also decreases postoperative adhesive obstruction.

#procedure

#surgical-critical-care

Reference:

Blumenstein I, Shastri YM, Stein J. Gastroenteric tube feeding: techniques, problems and solutions. World J Gastroenterol. 2014 Jul 14;20(26):8505-24.

Cirrhosis after JIB

 Q: 45 years old male status post Jejunoileal bypass (JIB) 13 years ago for obesity is now admitted for a possible liver transplant. Reversal of the jejunoileal bypass should be performed? (select one) 

 A) prior to transplant 

B) with the transplant 

C) should not be performed 

Answer: B 

JIB is an effective procedure with an intent to create therapeutic short bowel syndrome, but now rarely get performed due to its various complications including cirrhosis, electrolyte imbalance, and kidney failure. A surgeon may still consider it in patients with high morbid obesity. Cirrhosis can occur in up to 30-40 percent of the patients over the course of years. The treatment is a liver transplant. 

Most of these patients require reversal of the jejunoileal bypass. Reversal of bypass prior to transplant carries the risk of further hepatic decompensation (choice A). It can be either performed with the transplant or in some cases after the transplant in patients who develop a progressive liver injury.

#hepatology

#transplant

#surgical-critical-care

References:

1. Hocking MP, Davis GL, Franzini DA, Woodward ER. Long-term consequences after jejunoileal bypass for morbid obesity. Dig Dis Sci 1998; 43:2493. 

2. D'Souza-Gburek SM, Batts KP, Nikias GA, et al. Liver transplantation for jejunoileal bypass-associated cirrhosis: allograft histology in the setting of an intact bypassed limb. Liver Transpl Surg 1997; 3:23. 

3. Markowitz JS, Seu P, Goss JA, et al. Liver transplantation for decompensated cirrhosis after jejunoileal bypass: a strategy for management. Transplantation 1998; 65:570. 

4. Lowell JA, Shenoy S, Ghalib R, et al. Liver transplantation after jejunoileal bypass for morbid obesity. J Am Coll Surg 1997; 185:123.

Topiramate in pseudotumor cerebri

 Q: Why Topiramate, an antiseizure drug is considered one of the drugs of choice for the treatment of Idiopathic intracranial hypertension (pseudotumor cerebri). What makes it eligible? 

 Answer: It is true that Acetazolamide still holds a place as the first line of drug for the treatment of idiopathic intracranial hypertension (IIH), popularly known as pseudotumor cerebri. Acetazolamide is a carbonic anhydrase inhibitor and reduces cerebrospinal fluid (CSF) production. 

Topiramate is an antiseizure medication but also carries the property of inhibiting that carbonic anhydrase activity. Allegedly, the same mechanism plays a role in its efficacy for the treatment of migraines. It is found to have equivalent efficacy in the treatment of IIH as acetazolamide. It also improves symptoms of IIH including visual field loss.  It is also known to cause weight loss, another target desired in the treatment of IIH.

#neurology

References:

1. Celebisoy N, Gökçay F, Sirin H, Akyürekli O. Treatment of idiopathic intracranial hypertension: topiramate vs acetazolamide, an open-label study. Acta Neurol Scand 2007; 116:322. 

2. Shah VA, Fung S, Shahbaz R, et al. Idiopathic intracranial hypertension. Ophthalmology 2007; 114:617. 

3. Friedman DI, Eller PF. Topiramate for the treatment of idiopathic intracranial hypertension. Headache 2003; 43:592. 

Bystander hemolysis

 Q: 22 years old Afro-American male with a known history of sickle cell disease (SCD) - recently discharged from the hospital - is admitted back to ICU with sickle cell crisis and severe anemia. Hemoglobin (Hb) is reported as 3 g/dL Two weeks ago, on discharge, his Hb was 8 g/dL after he received two units of pRBC. Hematology fellow wrote the diagnosis of bystander hemolysis. What is bystander hemolysis?

Answer: Patients with sickle cell disease (SCD) often develop a delayed hemolytic transfusion reaction, after a week or two of pRBC infusion. The term was introduced by Drs. Petz and Garratty in 1997 as: " immune hemolysis of RBCs that are negative for the antigen against which the relevant antibody is directed." Allegedly activation of complement system is involved. The treatment is threefolds: avoidance of transfusion, steroids, and enhancing erythropoiesis. Recently, immune-modulating medications such as rituximab have been tried in cases of Delayed Hemolytic Transfusion Reactions (DHTR).

#hematology

References:

1. Scheunemann LP, Ataga KI. Delayed hemolytic transfusion reaction in sickle cell disease. Am J Med Sci. 2010;339(3):266-269. doi:10.1097/MAJ.0b013e3181c70e14 

2. Petz LD, Calhoun L, Shulman IA, et al. The sickle cell hemolytic transfusion reaction syndrome. Transfusion. 1997;37:382–392. 

3. Garratty G. Severe reactions associated with transfusion of patients with sickle cell disease. Transfusion. 1997;37:357–361.

Carbimazole

Objective of the question: To introduce carbimazole and its equivalency to methimazole in the treatment of severe symptomatic Grave's disease

Q:  27 years old female is admitted to ICU with severe symptomatic Grave's disease. Pharmacy informed you that methimazole is unavailable but carbimazole can be made available. If carbimazole is used to treat Grave's disease, its conversion in the body is? (select one) 

A) higher than methimazole 

B) lower than methimazole

Answer: A

Although not approved in the USA, in few countries Carbimazole is more readily available than methimazole. It is a prodrug and gets metabolized to methimazole in the body and provides almost 25-40% higher concentration than intended.

The dose in severe symptomatic Grave's disease is 20 to 40 mg/day

#endocrinology

References:

Page SR, Sheard CE, Herbert M, Hopton M, Jeffcoate WJ. A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism. Clin Endocrinol (Oxf). 1996 Nov;45(5):511-6. doi: 10.1046/j.1365-2265.1996.00800.x. Erratum in: Clin Endocrinol (Oxf) 1997 Feb;46(2):240. PMID: 8977745. 

MALA and HD

 Q: The goal of hemodialysis in metformin overdose is to remove the drug from the body? 

 A) True 

B) False 

 Answer: B

The goal of hemodialysis (HD) in metformin overdose is to correct Metformin-Associated-Lactic-Acidosis (MALA). HD in MALA should be performed with a bicarbonate buffer with a target of lactic acid below 3 mmol/L and/or the pH above 7.35. 

To bridge the gap between MALA and logistic arrangements of HD, sodium bicarbonate infusion can be used to keep pH above 7.1, or 7.2 if signs of end-organ damage are present.

#toxicology

#nephrology

#acid-base

References:

1. Calello DP, Liu KD, Wiegand TJ, et al. Extracorporeal Treatment for Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workgroup. Crit Care Med 2015; 43:1716. 

2. Lalau JD, Lacroix C, Compagnon P, et al. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995; 18:779.

methotrexate-induced pulmonary toxicity

 Q: 42 year old female who was started on methotrexate few months ago admitted to ICU with shortness of breath and hypoxemia. She required BiPAP to keep saturation > 90. All of the following are included in criteria to diagnose methotrexate-induced pulmonary toxicity EXCEPT? (select one) 

A) Hypersensitivity pneumonitis 

B) Radiographic evidence 

C) Negative Blood cultures 

D) Productive cough 

E) WBC count ≤15,000 cells/mm3

Answer: D

The diagnosis of methotrexate-induced pulmonary toxicity takes into account various factors including clinical, radiological, and bronchoalveolar lavage (BAL) findings, results of lung biopsy, and response to drug discontinuation. In patients taking methotrexate:

Major criteria are three: 

1. Hypersensitivity pneumonitis by histopathology without evidence of pathogenic organisms 
2. Radiographic evidence of patchy or diffuse pulmonary ground glass or consolidative opacities 
3. Negative blood cultures and initial sputum cultures are negative 

 Minor criteria are five: 

1. Shortness of breath for less than 2 months 
2. Nonproductive cough 
3. Oxygen saturation ≤90 percent on room air at the time of initial evaluation 
4. DLCO ≤70 percent of predicted for age 
5. Leukocyte count ≤15,000 cells/mm3 

"Definite" methotrexate pneumonitis is:

major criteria 1 or 2 and 3 with 3/5 minor criteria.

 "Probable" methotrexate pneumonitis is:

major criteria 2 + 3 with 2/5 minor criteria

#rheumatology

References;

1. Searles G, McKendry RJ. Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol 1987; 14:1164. 

2. Kremer JM, Alarcón GS, Weinblatt ME, et al. Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum 1997; 40:1829.

acute uremic encephalopathy

 Q: What is the usual lag time of recovery in acute uremic encephalopathy? 

Answer: About 24-48 hours after dialysis

Acute uremic encephalopathy is one of the indications of emergent dialysis, though the lag time for recovery is about 24-48 hours. Symptoms range from just fatigue to seizures and coma. Some patients may have a unique finding consisting of myoclonic jerks, twitching, or fasciculations known as uremic twitch-convulsive syndrome.

#nephrology

#neurology

References:

1. Bolton CF, Young GB. Uremic encephalopathy. In: Neurological Complications of Renal Disease, Bolton CF, Young GB (Eds), Butterworths, 1990. p.44. 

2. Lacerda G, Krummel T, Hirsch E. Neurologic presentations of renal diseases. Neurol Clin. 2010 Feb. 28(1):45-59 

3. Brouns R, De Deyn PP. Neurological complications in renal failure: a review. Clin Neurol Neurosurg. 2004 Dec. 107(1):1-16. 

4. Bansal VK, Bansal S. Nervous system disorders in dialysis patients. Handbook of Clinical Neurology. 2014. Vol 119 (3rd series):395-404.

predictor of poor outcome after transplant

 Q: Which of the following test predicts poor outcomes in patients undergoing heart-lung transplantation for idiopathic pulmonary hypertension (IPAH)? 

 A) High bilirubin 

 B) High LDH 

C) High hemoglobin 

D) High platelets 

 Answer: A

Pre-transplant high or persistent bilirubin level is found to be a good predictor of poor outcome in heart, lung, or heart-lung transplantation. This is probably due to high right atrial pressure causing hepatic congestion. Few suspected etiologies are valvular heart disease, ascites at transplant, and an old donor heart.

#transplantation

References:

1. Kramer MR, Marshall SE, Tiroke A, Lewiston NJ, Starnes VA, Theodore J. Clinical significance of hyperbilirubinemia in patients with pulmonary hypertension undergoing heart-lung transplantation. J Heart Lung Transplant. 1991 Mar-Apr;10(2):317-21. PMID: 2031931.

2. Chokshi A, Cheema FH, Schaefle KJ, Jiang J, Collado E, Shahzad K, Khawaja T, Farr M, Takayama H, Naka Y, Mancini DM, Schulze PC. Hepatic dysfunction and survival after orthotopic heart transplantation: application of the MELD scoring system for outcome prediction. J Heart Lung Transplant. 2012 Jun;31(6):591-600. doi: 10.1016/j.healun.2012.02.008. Epub 2012 Mar 27. PMID: 22458996; PMCID: PMC3358427.

Haptoglobin

 Q: Haptoglobin is an acute phase reactant?

A) True

B) False

Answer: A

Haptoglobin is an acute phase reactant and may be elevated in any inflammation. This bears an important clinical implication. It has a good negative specificity. A normal or elevated haptoglobin does not rule out hemolysis. In contrast, an undetectable haptoglobin level is almost consistent with hemolysis. 

As a rule of thumb, a haptoglobin level of 25 mg/dL can be considered a reliable cutoff point to rule out hemolysis. Ideally, haptoglobin level should be read with other indices of hemolysis such as LDH and indirect bilirubin.

#hematology

#laboratory science

References:

1. Marchand A, Galen RS, Van Lente F. The predictive value of serum haptoglobin in hemolytic disease. JAMA 1980; 243:1909. 

2. Stahl WM. Acute phase protein response to tissue injury. Crit Care Med 1987; 15:545.

3. Andersen CBF, Stødkilde K, Sæderup KL, Kuhlee A, Raunser S, Graversen JH, Moestrup SK. Haptoglobin. Antioxid Redox Signal. 2017 May 10;26(14):814-831. doi: 10.1089/ars.2016.6793. Epub 2016 Nov 8. PMID: 27650279. 

4. Shih AW, McFarlane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol. 2014 Apr;89(4):443-7. doi: 10.1002/ajh.23623. PMID: 24809098. 

5. Levy AP, Asleh R, Blum S, Levy NS, Miller-Lotan R, Kalet-Litman S, Anbinder Y, Lache O, Nakhoul FM, Asaf R, Farbstein D, Pollak M, Soloveichik YZ, Strauss M, Alshiek J, Livshits A, Schwartz A, Awad H, Jad K, Goldenstein H. Haptoglobin: basic and clinical aspects. Antioxid Redox Signal. 2010 Feb;12(2):293-304. doi: 10.1089/ars.2009.2793. PMID: 19659435.

FUO-outcomes

 Q: Patients who continue to have 'Fever of Unknown Origin' (FUO) despite extensive workup should be followed closely as they tend to have a poor clinical outcome. This statement is?

A) True

B) False

Answer: B

Although the underlying pathology plays an essential role in the outcome of FUO, most patients, particularly the pediatric population tend to have a good outcome. In general, only one-fifth of these patients get diagnosed in the outpatient follow-up of at least 8 weeks. 

Some respond to courses of glucocorticoids or nonsteroidal anti-inflammatory drugs (NSAIDs).

#ID

References:

1. Vanderschueren S, Knockaert D, Adriaenssens T, et al. From prolonged febrile illness to fever of unknown origin: the challenge continues. Arch Intern Med 2003; 163:1033. 

2. Zenone T. Fever of unknown origin in adults: evaluation of 144 cases in a non-university hospital. Scand J Infect Dis 2006; 38:632. 

3. Bleeker-Rovers CP, Vos FJ, de Kleijn EM, et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore) 2007; 86:26. 

4. Knockaert DC, Dujardin KS, Bobbaers HJ. Long-term follow-up of patients with undiagnosed fever of unknown origin. Arch Intern Med 1996; 156:618.