Friday June 29, 2007
Difference between Lactate Ringer's and Normal Saline solutions

Lactated Ringer's Solution was invented about 125 years ago by a British physiologist Sydney Ringer and never lost a day in its popularity. Let see its difference from normal saline.

Normal Saline is the solution of 0.9% NaCl. It has a slightly higher degree of osmolality compared to blood. One litre of Normal Saline contains

154 mEq/L of Na+ and
154 mEq/L of Cl−

Lactated Ringer's (per litre) Solution contains:

130 mEq/L of Na+ but total cations of 137 mEq/L , so still is isotonic.
109 mEq/L of Cl−
28 mEq/L of lactate
4 mEq/L of potassium
3 mEq/L of calcium.

Lactate converts to bicarbonate in liver.

Bonus Pearl: Patients with lactic acidosis usually have inadequate liver metabolism of lactate so conversion to HCO3- from the infused lactate of LR is impaired and may give false readings of serial lactate measurements but may be a better choice in regular situations where hyperchloremia restricts use of normal saline.

Wednesday June 27, 2007
Heparin rebound phenomenon

Heparin rebound phenomenon, is considered to be a contributive factor in excessive postoperative bleeding after cardiac surgery. It is due to the reappearance of anticoagulant activity despite adequate neutralization with protamine.This phenomenon is well known since atleast last 45 years 1.

The underlying etiology is due to the fact that a significant amount of heparin remains bound to plasma proteins and escape neutralization by protamine. Later this heparin get released and may contribute to excessive postoperative bleeding after cardiac surgery. Though logically, the treatment is more administration of prtoamine but caution should be taken as high and inappropriate protamine dose may lead to 'acute' pulmonary hypertension 2 and interestingly failed to show decrease in blood product adminstration 3 or any difference in the thrombelastographic profiles or coagulation screen (PT, PTT, ACT and platelets) 2. Also life threatening protamine reactions is another risk need to be considered 5.


Note: This Heparin rebound phenomenon is different from Rebound increase in Thrombin Generation and Activity after cessation of intravenous heparin in patients with acute coronary syndromes which is also often referred as heparin rebound phenomenon 4.



References: click to get abstract/article

1. Heparin rebound phenomenon in extracorporeal circulation - Surg Gynecol Obstet.1962 Aug;115:191-8.
2. Heparin rebound phenomenon--much ado about nothing? - Blood Coagul Fibrinolysis. 1992 Apr;3(2):187-91.
3. Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery? - J Thorac Cardiovasc Surg 2004;128:211-219
4. Rebound Increase in Thrombin Generation and Activity After Cessation of Intravenous Heparin in Patients With Acute Coronary Syndromes - Circulation. 1995;91:1929-1935.
5. Life Threatening Protamine Reactions In Cardiac Surgery: Literature Review With A Case Report - The Internet Journal of Thoracic and Cardiovascular Surgery. 2005. Volume 7 Number 1

Thursday June 21, 2007
Calcium infusion and thrombophlebitis

One important factor while writing order for IV calcium is of central line availability. If central line is not available, it is better to write order for calcium gluconate instead of calcium chloride. Calcium infusion tends to cause thrombophlebitis and chances are higher with calcium chloride as it contains 3 times more elemental calcium in camparison to same dose of calcium gluconate.

1 gram of Calcium gluconate contains 4.65 mEq of elemental Calcium, and
1 gram of Calcium chloride contains 13.6 mEq of elemental Calcium.

Wednesday June 13, 2007
Hypotension from intravenous Amiodarone

Continuing our theme from yesterday on Amiodarone, it would be of interest to know that hypotension from IV amiodarone bolus is mostly not due to amiodarone itself but due to its solubilized vehicle called polysorbate 80.

Polysorbate 80 itself can decreases heart rate by depressing AV nodal conduction and has property of increasing atrial and ventricular myocardial refractory period but can cause hypotension due to histamine releasing effect.

Polysorbate 80 is also blamed for Acute amiodarone-induced hepatitis but literature is scant on it.


References: click to get abstract/article

1. Pharmacology and Toxicology of a New Aqueous Formulation of Intravenous Amiodarone (Amio-Aqueous) Compared with Cordarone IV. - American Journal of Therapeutics. 12(1):9-16, January/February 2005.

2. Effects of amiodarone with and without polysorbate 80 on myocardial oxygen consumption and coronary blood flow during treadmill exercise in the dog - J Cardiovasc Pharmacol. 1991 Jul;18(1):11-6.

3. Histamine-releasing properties of Polysorbate 80 in vitro and in vivo: correlation with its hypotensive action in the dog - Agents Actions, 1985 Sep;16(6):470-7.

4. I.V. Amiodarone: What Do We Really Know About It? Cardiac Electrophysiology Review, Volume 2, Number 1 / March, 1998

5. Early acute hepatitis with parenteral amiodarone: a toxic effect of the vehicle? - Gut, Vol 34, 565-566, 1993

Tuesday June 12, 2007
Bedside tip !

If you opt to use intravenous Amiodarone, try to give it via central line as phlebitis is a common side effect, if given peripherally. It is reported in upto 16% 1 of cases particularly if given beyond 24 hours.



Related previous pearls:

Why we call it Am-iod-arone !
Amiodarone Neurotoxicity !
Amiodarone pulmonary toxicity



References: click to get abstract/article

1. Amiodarone as a First-Choice Drug for Restoring Sinus Rhythm in Patients With Atrial Fibrillation - Chest. 2000;117:1538-1545

Saturday June 9, 2007
The calcium phosphate precipitation and microemboli via TPN

If a patient is receiving total parental nutrition (TPN) and develops respiratory compromise, TPN should be immediately stopped and inspected for any precipitation. The calcium phosphate precipitates, although rare can form and when infused acts like microemboli. A filter can be utilized to overcome the problem when infusing TPN. Other ways to avoid the problem

• Infuse TPN within 24 hours of preparation.
• Use Ca-gluconate instead of CaCl.
• Keep the Ca:PO4 ratio greater than 1:2.
• Keep the total amount of Ca and PO4 less than 45 mEq/L.

Read case report and very extensive discussion on this topic: Microvascular Pulmonary Emboli Secondary to Precipitated Crystals in a Patient Receiving Total Parenteral Nutrition - Chest. 1999;115:892-895


References (Clickable):

1. Calcium and phosphates compatibilities in parenteral nutrition admixtures Tunis Med. 2006 Nov;84(11):677-82

2. Intravenous in-line filters: filtering the evidence. Curr Opin Clin Nutr Metab Care. 2003 May;6(3):319-25

3. Total parenteral nutrition associated crystalline precipitates resulting in pulmonary artery occlusions and alveolar granulomas. Dig Dis Sci. 2003 Jul;48(7):1352-4.

4. Pulmonary deposition of calcium phosphate crystals as a complication of home total parenteral nutrition, Journal of Parenteral and Enteral Nutrition, Vol 13, Issue 2, 209-213

Friday June 8, 2007
What Dig. level makes you happy ?

Digoxin is known to provid reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function without improving mortality (DIG trial -The Digitalis Investigation Group trial) 1. Very interesting work published in JAMA about 3 years ago (about 3800 patients) as a followup of above trial - looking into mortality association with different Digoxin level 2 . What they found:

* SDC = serum digoxin concentration
* Patients were divided into 3 groups based on SDC at 1 month

• Patients with SDCs of 0.5 to 0.8 ng/mL had a 6.3% lower mortality rate compared with patients receiving placebo.
• No reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL,

And

• Patients with SDCs of 1.2 ng/mL and higher had an 11.8% higher absolute mortality rate than patients receiving placebo.

Study suggested that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL.


Read interesting article: DIGOXIN DELUSIONS (from ucsf.edu)



References: Click to get abstract

1. The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure, The Digitalis Investigation Group - NEJM, Vol 336, Feb 20, 1997, number 8

2. Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure -JAMA. 2003;289:871-878.

Thursday June 7, 2007
Tachyphylaxis Associated With Continous Cisatracurium (Nimbex)

Tachyphylaxis is common among patients treated with neuromuscular blockers and varies with clinical situation like burn patients are more prone to have resistance with pancuronium. Cisatracurium is a very common neuromuscular blocker prescribed in ICUs, particularly it is a prefered agent in patients with major organ failures as it has a clearance mechanism independent of organ function. Other advantges of cisatracurium is no vagolytic effects ( minor histamine-releasing properties) and less association with prolonged muscle weakness. One disadvantage of continuous cisatracurium therapy is possible tachyphylaxis after 48-72 hours and may require escalating dose of the drug.

Reference:

Tachyphlaxis Associated With Continous Cisatracurium Versus Pancuronium Therapy - Pharmacotherapy, Pharmacotherapy 22(7):823-830, 2002

Tuesday June 5, 2007
Prescribing vitamin B6 with linezolid

Linezolid is found to be associated with 2 major side effects: cytopenias and peripheral neuropathy 1. When Vitimain B6 (PYRIDOXINE) was prescribed for peripheral neuropathy, interestingly it was found to help in reversing cytopenias more than peripheral neuropathy 2 . Dose of vitamin B6 used was 50 mg PO once a day.So far we have only few case reports but Vitamin B6 is safe and inexpensive and most experts don't see any harm in prescribing it along with linezolid.


References: click to get article

1. Severe sensory neuropathy associated with long-term linezolid use - Neurology.2005; 64: 926-927
2. Reversal of linezolid-associated cytopenias, but not peripheral neuropathy, by administration of vitamin B6 - Journal of Antimicrobial Chemotherapy 2004 54(4):832-835

Saturday June 2, 2007
Linezolid infusion and exposure to light

Case: You have a patient diagnosed with vancomycin-resistant enterococci (VRE) and has been started on linezolid (Zyvox). While evaluating patient at bedside you saw a bag labelled with linezolid, due to infuse in 30 minutes. What would be your instruction to pharmacy ?

Answer: To protect the infusion bag of linezolid from light. Linezolid infusion bag need to be protected from light while awaiting infusion to avoid degradation. Once infusion is started, bag can be unwrap.Note: IV Zyvox may exhibit a yellow color that can intensify over time, but it is a benign effect and does not affect potency.


Reference: click to get abstract

1. Zyvox - rxlist.com