Q: Effects of Dabigatran (an oral Direct Thrombin Inhibitor) may get accentuated (increase) with all of the following drugs except?

A) quinidine, 
B) verapamil, 
C) amiodarone,
D) Proton Pump Inhibitors (PPI)



Answer: D

Absorption of Dabigatran may be moderately decreased if taken with a proton pump inhibitor. Drug excretion through P-glycoprotein pumps is slowed in patients taking strong p-glycoprotein pump inhibitors such as quinidine, verapamil, and amiodarone, thus raising plasma levels of dabigatran. 

Tei Index

Q: What is Tei Index?


Answer:  The Tei index is increasingly used to evaluate and described cardiac function. The Tei index is easily derived using conventional pulsed Doppler echocardiography. It is Doppler-derived time interval index that combines both systolic and diastolic cardiac performance. The mean normal value of the Tei index is

• 0.39 ± 0.05 for the LV, and
• 0.28 ± 0.04.11 for the RV

Higher index values correspond to more pathological states with overall cardiac dysfunction.

A note on use of Methyl Prednisolone in acute Reversal of anti-platelets

There is some literature that exist on rapid reduction in the platelet inhibition following intravenous injection of methyl prednisolone in patients receiving clopidogrel, aspirin and other thienopyridines - who may be acutely bleeding. The beneficial effect of methyl prednisolone is may be due to ADP-mediated platelet inhibition. Rapid reversal of antiplatelet activity by steroid, particularly in intra-cranial bleed patients, is of interest and significance as it may prevent hematoma expansion. No specific dose is specified but any dose from 20-80 mg can be used.

Q: During resuscitation in "acute hemorrhagic shock" what is the ratio of IVF in expanding intravascular volume?


Answer: 3:1

As crystalloids quickly leak from the vascular space, each liter of IVF (NS or LR) expands the blood volume by 20-30%; therefore, in general, about 3 L of IVF is needed to be administered to raise the intravascular volume by 1 Litre. 

Q: 46 year old female with no history of tobacco smoking presented to ER with shortness of breath, fever and hypoxia requiring BiPAP mask. CXR showed right sided pleural effusion. Patient is admitted to ICU. You performed bedside ultrasound. Which features may alert you that this may be a malignant pleural effusion?

Answer: Ultrasound of pleural effusion can have a specificity of 100% at diagnosing malignant pleural effusions, if following features can be identified.

• visible pleural metastases
• pleural thickening greater than 1 cm
• pleural nodularity
• diaphragmatic thickening measuring greater than 7mm and 
• an echogenic swirling pattern visible in the pleural fluid

References:

1. Qureshi NR, Rahman NM, Gleeson FV (February 2009). "Thoracic ultrasound in the diagnosis of malignant pleural effusion". Thorax 64 (2): 139–43.

2. Chian CF, Su WL, Soh LH, Yan HC, Perng WC, Wu CP (July 2004). "Echogenic swirling pattern as a predictor of malignant pleural effusions in patients with malignancies". Chest 126 (1): 129–34

Understanding Dialysis Disequilibrium Syndrome (DDS) - "Reverse Urea Effect"

Urea usually has a lag of inherent delay of entry into the brain, means that urea can function as a temporary effective osmole, which couples the faster movement of water in the opposite direction. This effect is called the “urea effect”.

Conversely, when urea is removed from the blood after equilibration between the blood and the brain has been achieved, the lag in the exit of urea from the brain into the blood can draw water into the brain, thus engendering cerebral edema. This process has been termed the “reverse urea effect”. To make things worse, the lag in urea exit from the brain may be magnified in patients with renal failure.
DDS is related to the “reverse urea effect”. The syndrome was attributed to the delayed exit of urea from the brain in the face of a rapid dialysis-induced decline in blood urea level, thus creating an osmotic gradient that favored the shift of water into the brain from the blood.

A note on Sodium (Na) correction in severe hyperglycemia

To correct Sodium (Na) in hyperglycemia above 200 mg/dL the most commonly used correction factor is a 1.6 mEq per L increase in serum sodium for every 100 mg per dL increase in glucose concentration. 

 At least one study argue that this correction factor may not work if glucose is more than 500 mg/dL. The authors conclude that the conventional correction factor used to correct serum sodium in patients with hyperglycemia is inaccurate and leads to serious underestimation of serum sodium values in association with glucose levels higher than 500 mg per dL. Therefore, the authors recommend using 2.4 as the correction factor to prevent such underestimations, particularly in patients with severe hyperglycemia who require more of a correction.



Reference:

Hillier TA, et al. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. April 1999;106:399–403. 

 Q: 53 year old male is in ICU recovering from DKA. Patient informed you that he has been prescribed an anti-hypertensive in topical form as a treatment for his pain from diabetic neuropathy. He prefers to use the same. Which one it could be?

Answer: Clonidine

Recently one study showed that clonidine could be an effective agent to use as a treatment to relieve pain from diabetic neuropathy.




Reference:

Campbell, CM; Kipnes, MS; Stouch, BC; Brady, KL; Kelly, M; Schmidt, WK; Petersen, KL; Rowbotham, MC; Campbell, JN (September 2012). "Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy"  -. Pain 153 (9): 1815–1823.

Q: What is the recommended target of MAP (Mean Arterial Pressure) in therapeutic hypothermia protocol?

Answer: More than/equal to 80

A mean arterial pressure (MAP) goal of more than 80 mm Hg is recommended in therapeutic hypothermia, as keeping blood pressure on hypertensive side is potentially additive to the neuroprotection of hypothermia. It should be ok to use low dose pressor if required to keep MAP > 80 mm Hg.

Q: Pyridostigmine (Mastinon) which is well known for its use in Myasthenia Gravis can also be use in which other common condition?

Answer: Orthostatic hypotension 

Pyridostigmine has been studied and found to be significantly effective to treat orthostatic hypotension. Beside Midodrine, this could be another nice drug to use in those frustrating situations in ICU where orthostatic hypotension delays transfer out of ICU. Usual dose is 60 mg PO up to 3 times per day.

Reference:

Gales BJ, Gales MA. (2007). "Pyridostigmine in the treatment of orthostatic intolerance". Annals of Pharmacotherapy 41 (2): 314–8

Singer W; Sandroni P; Opfer-Gehrking TL; Suarez GA; Klein CM; Hines S; O'Brien PC; Slezak J; Low PA. "Pyridostigmine Treatment Trial in Neurogenic Orthostatic Hypotension." Archives of Neurology, April 2006, Vol. 63, No. 4, pp. 513-518 .

Q: Which of the following may be used in treatment of massive "Fire Ants" exposure on human body?  

A) immediate application of urine

B) application of aloe vera gel

C) topical anesthetic benzocaine,

D) antihistamines

E) corticosteroid

F) All of the above

Answer: F 

Exposure to colony of fire ants may be fatal if it causes severe allergic  anaphylactic reactions to fire ant stings, but immediate and overall treatment is usually supportive. There is no specific antidote. If no immediate help is needed, human urine can be used for irrigation and to kill fire ants !!

Q: "Banana Bag" cab be used in which condition as an adjuvant treatment beside its use in alcoholism and nutritionally deficient patients?


Answer: Terminally ill patients to relieve pain

The contents of "Banana Bag" are 

•  Thiamine 100 mg 
• Folic acid 1 mg
•  MVI 1 amp (Multivitamin) 
• 3 grams of magnesium sulfate 

 Due to yellow color of MVI, solution is popularly named as "banana bag" in US hospitals. 

Banana Bags are very well known for its use in alcoholics, nursing home patients and nutritionally deficient patients, for need of thiamine to prevent Wernicke-Korsakoff syndrome and to replenish whole-body magnesium deficiencies. One less known but beneficial use of "Banana bag" in ICU can be for patients with terminal illness because magnesium can mitigate nerve pain and relieve muscle pain and cramps.

Q: Why in Delirium Tremens (DT) patients, IV Thiamine is preferred over PO Thiamine? 

 

Answer: Orally administered thiamine usually have poor enteral absorption in alcoholic patients, therefore high-risk patients who may go into DTs should  be given parenteral thiamine at 100-250 mg once daily for initial dew days till risk subsides.

Q: 57 year old male with 100 PPY of smoking history is admitted to ICU with COPD exacerbation. Patient developed mild delirium & psychosis in ICU though recovering from his COPD exacerbation and is now extubated.. Olanzapine was initiated by service but delirium and psychosis continue to get worse. What could be the reason?  

Answer: Olanzapine is metabolized by the cytochrome P450 system, principally by isozyme 1A2. By these mechanisms more than 40% of the oral dose is removed by the hepatic first-pass effect. Agents that increase the activity of CYP1A2, notably tobacco smoke significantly increase hepatic first-pass clearance of Olanzapine and decreases its effect

Q: 42 year old male is admitted to ICU with community acquired pneumonia. CXR showed significant unilateral pleural effusion. You decided to perform diagnostic pleural tap to send fluid for culture and sensitivity to guide antibiotic drainage. Initial report from lab showed PH of 7.14 of pleural fluid. What is your next step?  

 

Answer: Chest tube placement 

As famously known: “the sun should never set on a parapneumonic effusion”, PH lower than 7.20 of pleural fluid is the most powerful indicator to predict the need for chest tube drainage in patients with non-purulent, culture negative fluid.

Reference:

1.  Heffner JE, Brown LK, Barbieri C, DeLeo JM. "Pleural fluid chemical analysis in parapneumonic effusions. A meta-analysis". American Journal of Respiratory Critical Care Medicine 1995; 151(6):1700-8

2. Sahn SA, Light RW. The sun should never set on a parapneumonic effusion. Chest 1989;95:945-7.

Q: Why in comparison to others in same group Cefepime is considered 4th generation Cephelosporin? 


Answer: Cefepime is an extended-spectrum cephalosporin active against a broad spectrum of gram-positive and gram-negative aerobic bacteria. The gram-positive spectrum is similar to that of cefotaxime, the gram-negative spectrum is similar to that of ceftazidime, and many, though not all, organisms resistant to these two agents remain susceptible to cefepime, prompting it to have fourth-generation designation. The reason thought to be as Cefepime has a decreased propensity to induce beta-lactamases compared with other beta-lactam antibiotics.

 Cephalosporins are β-lactam antibiotics, which are grouped into four generations according to their antibiotic spectrum of activity. The first generation has mainly gram-positive activity. The second and third generation has more gram-negative activity with mostly decreased activity against gram-positive bacteria. Few examples are: 

 •First Generation: cefazolin, cefalexin, cefadroxil 
•Second Generation: cefamandole, cefoxitin, cefuroxime, cefotetan
 •Third generation: cefotaxime, ceftriaxone, ceftazidime 
 •Fourth generation: cefepime, cefozopran, cefpirome, cefquinome

Q: After how many hours of Propofol infusion, hypertriglyceridemia may become an issue?

Answer: About 48 hours

Risk of hypertriglyceridemia ( > or = 400 mg/dl) and pancreatitis in ICU are

• median infusion rate of propofol around 50 microg/kg/minute
• median time around 54 hours (higher with longer duration of propofol infusion)
• Older age
• longer ICU stay
• Admission in medical ICU

Reference:

Devlin JW, Lau AK, Tanios MA. - Propofol-associated hypertriglyceridemia and pancreatitis in the intensive care unit: an analysis of frequency and risk factors.- .Pharmacotherapy. 2005 Oct;25(10):1348-52

Q: All of the following drugs can be given as epidural Except?

A) Morphine, 

B) Ketamine,

C) Clonidine

D) Lidocaine

E) Propofol

Answer: E (Propofol)

Propofol is obviously can't be given due to risk of sedation and has never been tried! Morphine, Ketamine and Lidocaine are well known to get used as epidulrals. Objective of above question is to bring to attention the use of Clonidine as an epidural.

It is well established that clonidine is an effective analgesic, and this is attributable to its α2-agonist activity. A tremendous amount of modulation of incoming pain signals occurs in the dorsal horn of the spinal cord prior to being sent to higher centers in the CNS. Messages are either strengthened or attenuated by release of various neurotransmitters by primary afferent Aδ or C fibers, interneurons, and descending bulbospinal fibers. Nociceptive stimuli will promote release of excitatory transmitters from primary afferents in the dorsal horn. To compensate, there is simultaneous release of norepinephrine from descending inhibitory bulbospinal neurons, which binds to α2-receptors in the dorsal horn to diminish afferent pain transmission, thereby producing analgesia.

Q: What is "Safe Triangle" to insert chest tube?

Answer: British Thoracic Society recommends the tube is inserted in an area described as the "safe triangle", a horizontal line at the level of the nipple and two muscles of the chest wall i.e., latissimus dorsi and pectoralis major. 

Reference:

Laws, D. "BTS guidelines for the insertion of a chest drain". Thorax 58 (90002): 53ii–59

Q: What is the risk of Re-Expansion Pulmonary Edema (REPE) after thoracentesis?

Answer:  0.18% per 1 ml of fluid removed

One study which span over 12 years and looked into 9320 inpatient thoracenteses on 4618 patients found following complication rates after the procedure 

• 0.61% - iatrogenic pneumothoraces
• 0.01% -  REPE and
• 0.18% - bleeding episodes.

 Iatrogenic pneumothorax was significantly associated with removal of >1500 mL fluid, unilateral procedures and more than one needle pass through the skin (as expected).

For every 1 mL of fluid removed there was a 0.18% increased risk of REPE.

Interestingly, There were no significant associations between bleeding and INR, PTT and platelet counts. 

Reference:

Mark J Ault, Bradley T Rosen, Jordan Scher, Joe Feinglass, Jeffrey H Barsuk - Thoracentesis outcomes: a 12-year experience - Thorax 2015;70:127-132

A note on inhaled Milrinone

(instead of systemic Milrinone)

The major advantage of inhaled milrinone is its pulmonary selectivity, thereby avoiding systemic side effects and ventilation-perfusion mismatch. Inhaled milrinone is an effective pulmonary vasodilator and appears to be an alternative promising approach in addressing the problem of right-ventricular decompensation following cardiopulmonary bypass.

Reference:

Wang H, Gong M, Zhou B, Dai A. - Comparison of inhaled and intravenous milrinone in patients with pulmonary hypertension undergoing mitral valve surgery. -  Adv Ther. 2009 Apr;26(4):462-8

Q: 58 year old male with CKD 3 (Chronic kidney Disease) is admitted to ICU with hypertensive crisis. Patient is started on Nitroprusside drip by an "Old fashioned ER Doc".  ICU fellow on call at night decided to "float swan" to determine volume status. After few hours of admission, patient went into undetermined lactic acidosis. Pulmonary artery catheter (PAC) progressively showed increase in SVO2. What is your concern?

A) Missed sepsis

B) Cyanide poisoning

C) Underlying Cirrhosis

D) Inadequate titration of drip

E) Artifact in PAC                            

Answer: Cyanide poisoning

High SvO2 accompanied by lactic acidosis indicates failure of the cells to extract. In nitroprusside toxicity, cyanide poisoning is well may be the cause, particularly in renal compromised patients. To make things complicated, possible early sign of cyanide toxicity is the acute resistance to the hypotensive effects of increasing doses of sodium nitroprusside.

Sepsis is a possibility but it usually presents with hypotensive shock. Similarly cirrhotic patients are usually hypotensive.

Q: Which group of drug may increase the chance of anaphylactoid reaction to intravenous contrast dye? 

Answer: Beta blockers 

Beside other risk factors including previous allergic reactions or underlying cardiac or respiratory disease, use of Beta-blockers has been found to be a risk factor for allergic type reaction to IV contrast.

Q: Which 2 group of drugs may increase the chances of Hypersensitive reactions (HSRs) to intravenous Iron infusion?

 

Answer: Beta blockers and ACE inhibitors

Few risk factors associated with high risk of HSRs to IV Fe infusion are previous reaction to IV Fe, fast infusion, history of various allergies, history of asthma, eczema or systemic inflammatory disease, concomitant use of beta blocker or ACE inhibitor, old age, or anxiety either on patient or staff part.

IV Fe infusion should not be given in first trimester of pregnancy and should be given with caution in severe underlying respiratory or cardiac illness.

Q: Which artifacts may commonly lead to high mixed venous oxygen saturation (SVO2)?

 

Answer: 

SvO2 (Mixed venous oxygen saturation) can be falsely elevated 

• if the tip of the pulmonary artery catheter is  in wedged position
• if the tip of the pulmonary artery catheter is positioned distally
• If excessive vacuum has been applied to the sampling syringe
• aspiration of air into the blood gas syringe during sampling
• the presence of an air bubble in the syringe or blood draw

Q: 24 year old male has been brought to ICU from ER after he was stuck at his workplace in a kitchen and was exposed to smoke inhalation for 15 minutes. Patient has clinically no respiratory symptoms and wants to go home after 6 hours in hospital (ER and ICU). Most of the labs and CXR are essentially normal. Carboxyhemoglobin level is 14% and earlier ABG was reported "essentially normal". Which one other lab you may like to do before sending patient home?

Answer: VBG (Venous blood gas) 

Patient should not be discharged from hospital if there is a history of closed-space exposure for longer than 10 minutes or if manifest  symptoms of carbonaceous sputum, bronchospasm, odynophagia or if workup shows arterial PO2 less than 60 mm Hg or any  metabolic acidosis or carboxyhemoglobin levels 15% or above. Often missed is VBG (venous blood gas) as if arteriovenous oxygen difference (on 100% oxygen) is greater than 100 mm Hg, patient should not be allowed to go home.

Borderline cases can be hard to decide as frequently symptoms develop late. This patient should be allowed to go home with high caution as there is already long exposure to smoke as well as carboxyhemoglobin level is almost at cut off of 15%.

Q: What are the 4 clinical stages of hepatic encephalopathy?

Answer:

First stage: Inverted sleep-wake pattern (sleeping by day, being awake at night).

Second stage: Lethargy and personality changes.

Third stage: Marked confusion.

Fourth stage: Coma

Q: Name at least 5 "non-infectious" complications of Peritoneal Dialysis?

Answer:

• Increase Intra-Abdominal Pressure
• Ventral Hernias
• Genital Edema
• Hydrothorax
• Hemoperitoneum
• Chyloperitoneum

A note on Vitamin C Resuscitation in "Burn Patient"

The landmark "Tanaka study" showed that high dose Vitamin C (ascorbic acid) during the first 24 hours after burn

•  reduced resuscitation fluid requirements by 40%, 
•  reduced burn tissue water content 50%

 All these eventually lead to reduced requirement for mechanical ventilation and reduced ventilator days. 


References: 

1. Tanaka H, Matsuda T, Miyagantani Y, et al: Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration. Arch Surg 2000; 135:326–331 

2. Dubick MA, Williams C, Elgjo GI, et al: High-dose vitamin c infusion reduces fluid requirements in the resuscitation of burn-injured sheep. Shock 2005; 24:139–144