Q: 54 year old male with ESRD (End Stage Renal Disease) admitted to ICU post-operatively. Patient has significant "oozing" from surgical site. Surgeon ruled out surgical bleed. You corrected coagulopathy and gave one dose of DDAVP (Desmopressin) with only partial response. Hematology recommends IV Estrogen. What is the dose?


Answer: Estrogens improve bleeding time and decrease clinical bleeding significantly particularly in uremic patients. The dose is 0.6 mg/kg IV over 30 minutes per day. It can be repeated upto 5 days.The time to onset of action is about 6 hours. Estrogens have also been successfully used in patients with GI bleed in patients with uremic platelet dysfunction.

Mechanism of action: It has been postulated that the hormones decrease production of L-arginine, which is a precursor of NO. By decreasing NO concentrations, which seem to be higher in uremia, there is less guanylyl cyclase stimulation and less production of cGMP. This potentially leads to increased production of TxA2 and ADP, which are crucial contributors to formation of platelet plugs. Also estrogen decrease antithrombin III and protein S levels, and increase factor VII concentrations, might contribute to the therapeutic effect in this clinical situation.

How much FFP?

Dr. Sam Schulman from Karolinska Hospital, Stockholm, Sweden wrote an excellent review on "Care of Patients Receiving Long-Term Anticoagulant Therapy" in August 14, 2003 issue of NEJM. Part of article suggest formula for amount of FFP (Fresh Frozen Plasma) to correct INR upto desired level in a bleeding patient from over-anticoagulation.

Amount of FFP needed(ml) =(target level as percentage - present level as percentage) x Wt.(kg)

The "percentage" is prothrombin complex, expressed as a percentage of normal plasma, corresponds to the mean level of the vitamin K–dependent coagulation factors. It can be compute easily with following table:

INR 1 = 100 (%)
INR 1.4 - 1.6 = 40
INR 1.7 - 1.8 = 30
INR 1.9 - 2.1 = 25
INR 2.2 - 2.5 = 20
INR 2.6 - 3.2 = 15
INR 4.0 - 4.9 = 10
INR > 5 = 5 (%)

Example: In a 70 kg patient bleeding with INR of 7.5 and if our target is to bring INR down to 1.4, using above table:

Total FFP needed = (40 - 5) x 70 = 2450 ml

(One unit FFP usually contains 200-250 ml of FFP)

Reference: click to get reference

Care of Patients Receiving Long-Term Anticoagulant Therapy - NEJM - Volume 349:675-683, August 14, 2003

Q: In Uremia (Choose one)?

A) PTT is prolonged, PT is normal, Platelet count normal, Bleeding time is prolonged.

B) PTT is prolonged, PT is normal, Platelet count is decreased, Bleeding time is normal

C) PTT is normal, PT is normal, Platelet count is decreased, Bleeding time is prolonged

D) PTT is prolonged, PT is prolonged, Platelet count is decreased, Bleeding time is normal

E) PTT is normal, PT is normal, Platelet count is normal, Bleeding time is prolonged

Answer is E

Uremia causes dysfuntion of platelet but there is no decrease in numbers. Uremia does not effect PT and PTT - so only bleeding time is prolonged.

Recommended Reading: (click) Evidence-based treatment recommendations for uremic bleeding: Stephanie J Hedges and coll., - Nature Clinical Practice Nephrology (2007) 3, 138-153

Q: What does types A, B and C stand for in hepatic encephalopathy?


Hepatic encephalopathy is subdivided in type A, B and C depending on the underlying cause.

Type A (=acute) describes hepatic encephalopathy associated with acute liver failure.

Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease.

Type C (=cirrhosis) occurs in patients with cirrhosis.

Q: What is the drug of choice to control cocaine induced seizures?


A: Diazepam and lorazepam.

Also, barbiturates, may be effective in controlling seizures because they may act synergistically with the benzodiazepines.

Important pearl to remember is: Phenytoin may not be effective against cocaine-induced seizures.

CABG vs Stents - 2 parts (from NEJM)

Click on play buttons

Q: Gastric fluid itself contains very little potassium (about 10 mEq/L) than why vomitting induces hypokalemia?


Answer: Vomitting induce volume depletion which causes hypokalemia by 3 systemic effects.

1. Volume depletion leads to secondary hyperaldosteronism, which, in turn, causes enhanced cortical collecting tubule secretion of potassium in response to enhanced sodium reabsorption.

2. Metabolic alkalosis which increases collecting tubule potassium secretion due to the decreased availability of hydrogen ions for secretion in response to sodium reabsorption.

3. Metabolic alkalosis directly enhances potassium entry into cells.

Q: Caspofungin may cause which electrolyte imbalance?


Answer: Hypokalemia

3-11% of patients may develop hypokalemia. Other adverse lab abnormalities include eosinophilia, anemia, decreased white blood cell count, elevations in liver function tests and serum bilirubin.

Q: 53 year old male with history of HIV is admitted to ICU with clinical signs of meningitis. Resident performed Lumbar Punture and called you with panic as opening pressure is noted to be 200 mm H2O. Whats your diagnosis?

Answer: Cryptococcosis

Cryptococcosisis is a systemic or central nervous system (CNS) fungal infection caused by the yeast Cryptococcus neoformans . Cryptococcal infection is usually asymptomatic and self-limited. In patients with advanced HIV infection (eg, those with CD4 counts less than 100 cells/µL), Cryptococcus may cause life-threatening illness, either from a new exposure or through reactivation of a previously acquired latent infection. One of the hallmark is elevated ICP. Elevated ICP significantly increases the morbidity and mortality of cryptococcal meningitis and should be treated by the removal of CSF. The CSF opening pressure should be checked on the initial LP. LP and CSF removal should be repeated daily as needed for ICP reduction. Ventriculostomy or a ventriculoperitoneal (VP) shunt may be needed if the initial opening pressure is more than 400 mm H2O, or in refractory cases.

Recommended Reading: EDITORIAL REVIEW: HIV-associated cryptococcal meningitis, Joseph N. Jarvis and Thomas S. Harrison, AIDS 2007, 21:2119–2129

Q: Does (Metronidazole) Flagyl crosses blood brain barrier? Yes OR No

Answer: Yes

Flagyl can cross blood brain barrier and so neurotoxicity and neuropathy due to it is underdiagnosed.

1. Metronidazole-Induced and Wernicke Encephalopathy: Two Different Entities Sharing the Same Metabolic Pathway? (Letter) -American Journal of Neuroradiology 29:e84, October 2008

2. Painful neuropathy due to skin denervation after metronidazole-induced neurotoxicity - J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2009.194118

Q: What are ESKAPE pathogens?

Answer: The ESKAPE pathogens are six bad bugs on the loose!

Enterococcus faecium,

Staphylococcus aureus,

Klebsiella species,

Acinetobacter baumannii,

Pseudomonas aeruginosa, and

Enterobacter species

These are biggest infectious threats in view of their rising resistance and no new novel antibiotics coming in pipeline!

Recommended Reading: (click) Progress and Challenges in Implementing the Research on ESKAPE Pathogens - Louis B. Rice, MD, Infect Control Hosp Epidemiol 2010;31:S7–S10

Zyprexa as anti-emetic

Olanzapine (Zyprexa) is an antipsychotic in the thienobenzodiazepine class that blocks multiple neurotransmitters in brain. Olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Studies have shown the effectiveness of olanzapine as an antiemetic. Olanzapine combined with a single dose of dexamethasone and a single dose of palonosetron is found to be very effective in controlling acute severe nausea.


Olanzapine as an Antiemetic in Refractory Nausea and Vomiting in Advanced Cancer - Journal of Pain and Symptom Management, Volume 25, Issue 6, Pages 578-582 (June 2003)

Q: What is the difference between filgrastim (Neupogen) and pegfilgrastim (Neulasta)?


Answer:

Filgrastim (Neupogen): is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes in neutropenic patients. It can be given subcutaneously or intravenously. Usual dose is 5 mcg per kg of weight daily.

Pegfilgrastim (Neulasta): When compared to filgrastim, pegfilgrastim has an added polyethylene glycol molecule which reduces renal clearance and prolongs persistence in vivo (half life range: 46-62 hours). Pegfilgrastim can be given on the first day of chemotherapy.The effects of one dose of pegfilgrastim last fourteen days. It can only be given subcutaneously and not intravenously. The recommended dosage is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle.