Norepinephrine or Dopamine?

It looks like...we may have a winner. Yes
Im talking about the use of vasopressors in the setting of septic shock. There have been a few clinical trials done to see if one vasopressor is better than the other in terms of mortality from septic shock. (the latest one was from SOAP 2 trial from NEJM 2010)We didnt have a clear result so far.

But  a recent meta analysis of the trials have shown that norepinephrine might be better than Dopamine. It is associated with a 9% reduction in in-hospital and 28 day mortality in patients with septic shock. Patients on Dopamine had significantly increased incidence of cardiac arrhythmias compared to norepinephrine. This is probably the reason behind the poor performance of Doapmine...as we all know that arrhythmias can hinder cardiac function. The same finding of increased cardiac arrhythmias with Dopamine was also noted in the above SOAP trial.
The above meta-analysis was done at Thomas Jefferson University.(J of Int Care Med ...March 2011)

Would be reasonable to use nor-epinephrine as the first line vasopressor for patients with septic shock. Infact according to the SOAP trial,dopamine was associated with an increased 28 day mortality in patients with cardiogenic shock, as compared to norepinephrine!

The "Duty to warn" !!

We had a young female with HIV for 10 years,who came with an infected condyloma. She has had previous MAC, vulval cancer and cervical dysplasia  in the past. She has been with her partner for last 1 year, and they are sexually active,and use protection everytime. But when enquired, she said that the partner does not know about her HIV status , and she did not want to disclose this to him .Now.......do we have to honour her wish or...do we have to let the partner know?? Lets see what Connecticut law tells us.....(beware..this may not be true for other states!)

The term “duty to warn” refers to situations in which a  physician may learn that a patient is engaging in unsafe sex without having disclosed his or her HIV-positive status to the partner.
Connecticut law permits both public health officers and physicians, under certain circumstances, to inform or warn partners that they may have been exposed to HIV.The term “partner” means an “identified spouse or sex partner of the protected individual or a person identified as having shared hypodermic needles or syringes with the protected individual.” The requirements for such a disclosure by a public health officer are that:

1.There is a reasonable belief of a significant risk of transmission to the partner.

2.The public health officer has counseled the individual regarding the need to notify a partner and reasonably believes that the individual will not disclose to the partner; and

3.The public health officer has informed the protected individual of his or her intent to make the disclosure.

A physician may only warn or inform a known partner if both the partner and the individual with HIV are under the physician’s care. A physician may also disclose confidential HIV related information to a public health officer for the purpose of warning partners, if the physician takes the same steps with respect to his or her patient as public health officers must take above.

In making such a warning, the physician or public health official shall not disclose the identity of the HIV-infected individual and, where practicable, shall make such disclosure in person.

Well...this is still an evolving area of ethics, and might change in the future. Hope this helps.....and this is a sensitive issue to be dealt.

Antihypertensives - a little pharmacology helps

I came across this article recently about some interesting facts about antihypertensive medications and their pharmacology, which I though will be useful for practising clinicians like us!
The article describes about all 4 major types of antihypertensives. But the one which stands out is the angiotension converting enzyme inhibitors----WHY?     due to their difference in pharcological actions compared  to others.Let me start with a question..
If Mr.X tolerates(no hypotension) 5mg of Lisinopril, can we increase the dose to 40mg straightaway?

Most of us would say "NO". But the author says yes....and the explanation is pretty simple, interesting and true!
Unlike the other antihypertensives(beta blockers,CCB,diuretics), ace-i do not have a linear dose-response relationship....meaning that their BP lowering effect is not proportional to the dose. In other words....the efficacy of ace-i is the same irrespective of their dosage. Again...to make it more simple...a dose of 5mg of Lisinopril will lower the BP to the same extent as 40mg of Lisinopril. So why give 40mg in place of 2.5 mg? Well...the dose correlates with the duration of action.the higher the dose...the longer the duration of action!(Brit J Pharm 1984!)
It looks like...we have the low doses of ace-i in the market mainly to be used in patients with heart failure (who might have a low BP due to their other meds) to see if they can tolerate any hypotension induced by addition of ace-i. Also, the common side effect of ace-i...COUGH ..is not dose related.So here again..the dose doesnt matter.

So the article concludes that..ace-i don't have a linear dose-response curve, and so their dose can be increased to the maximal dose without any major concerns for hypotension. But ...one aspect of ace-i that the article doesn't discuss...is hyperkalemia. Well..the risk of hyperkalemia with ace-i is dose related, and whether it would be a good idea to go for a maximal dose straightaway or to increase it gradually, in this aspect.So..bottom line-----beacuse of the risk of hyperkalemia..we may not be able to go to a maximal dose directly, and not because of risk of hypotension.
A quick word abt hyperkalemia with ace-i : the risk is quite low on its own. The risk is high in CKD(4 fold risk), hepatic disease(almost 5 fold risk), taking>15 tablets(5 to 9 fold risk), advanced age(twice likely)...
(Pharm W Sci 2009)

Finally..the above article was published in American J of Cardio vasc Drugs 2011. The graph(above) is a modified graph from the same study. 

Spontaneous bacterial peritonitis

An acute bacterial infection of ascitic fluid. Happens in people with ascites due to any etiology(even with CHF, Budd chiari !!!). The route of infection is still not entirely clear. It may be a simple translocation of bacteria from the gut due to bacterial overgrowth  (as previously thought), or from hematogenous spread. But in general its the gut bacteria which accounts for most of SBP. This is mainly due to reduced intestinal transit times in pts with cirrhosis, along with low protein and complement levels etc.
The common bugs are E.Coli, Klebsiella and Strep pneumoniae.
Diagnosis is based on diagnostic aspiration of the ascitic fluid. We all tap the ascitic fluid in someone with symptoms of infection(fever, abdominal pain, tenderness etc). But around 30% of pts with SBP might not have any symptoms!! So...what shall we do?.........One of our gastroenterologist says...."JUST TAP ALL ASCITES". Well...he might be right...given a mortality range of 30-70% for SBP!


Based on the tap....it can be classified as follows...
1.SBP - if >250 PMN/micL  AND positive culture.
2.Culture-negative neutrocytic ascites -ascitic fluid culture is negative, but PMN count is ≥ 250 cells/µL. 
3. Monomicrobial nonneutrocytic bacterascites - positive culture result with a PMN count ≤ 250 cells/µL.
Irrespective of what type it is!!!......they all need to be treated based on clinical suspicion.


A very simple method being used these days(mostly in Europe) to diagnose SBP is the simple Leukocyte esterase test, which can be done at bedside. It has a sensitivity & specificity of 100 % & 91% resp to diagnose SBP! ( E Jof Gastro Hep 2007)
What to treat with -- A 3rd generation Cephalosporin or a fluroquinolone. Its rare to have anaerobic SBP , as ascitic fluid is rich in Oxygen!


When to use albumin - One of the main causes of mortality in SBP is due to development of renal failure. Albumin in addition to antibiotics have shown to prevent renal impairment and also to reduce mortality by around 10 to 15%based on this randomised trial(NEJM 1999). Its given as 1.5 g/kg at diagnosis and 1 g/kg on Day3.There is another randomised trial underway in Brazil to add more evidence to this practice.(ALTERNATE trial). 


Prohylaxis for SBP - Well..there are a group of patients who will benifit from prophylaxis. They are 1.anyone with a previous episode of SBP reducing mortality by 25% over a 1 year period(Hepatology 1990)  2. GI bleed with a course of 7 days.  3.pts with ascitic fluid protein <1 g/dl plus one of the following --- creatinine >1.5, bilirubin>4.(Hepatology 1995) The last criteria is a soft call, and would depend on local practice.The last two indications are a short course(1 -2 weeks) of antibiotics.The first indication is a longer term prophylaxis (1 year or more). Norfloxacin 400 daily is a preferred drug(as it selectively targets Gram negatives, and leaves anaerobes !)

Iron and Iron defeciency anemia - quick recap

Eventhough we have read about Iron deficiency and anemia for a while now, we kind of need some reinforcements from time to time.(I....definitely need some!!). 
Lets start with the iron  panel (well ...never forget to examine and correlate with the pt history & findings!)

IRON PANEL - A normal adult body contains 3-4 grams of iron; about 2 grams is stored in hemoglobin, about 400mg in iron-containing proteins, about 3-7 mg is bound to transferrin in plasma, and the remaining iron is stored as ferritin and hemosiderin (an iron storage complex found within cells). Transferrin saturation(TSAT) & total iron binding capacity(TIBC) are 2 common tests done. TSAT essentially measures the same thing as TIBC. Total iron binding capacity indicates how much room there is for iron, while TSAT shows how much iron is currently saturating transferrin. Usually transferrin is about 1/3 full of iron: serum iron (Fe) divided by TIBC = 1/3. TSAT is reduced in patients with IDA and often in patients with anemia of chronic disease.

Ferritin is the cellular storage protein for iron in tissues found in the intestines, liver and spleen which contain approximately 20% iron.In general, TSAT < 20 &/or ferrtin<200ng/dl are considered to be iron deficient.


CALCULATE IRON DEFICIT - (especially if rapid replenishment is planned) - First, calculate the patient’s hemoglobin deficit by subtracting their current hemoglobin from the goal of 14g/dL. Second,calculate the body’s total hemoglobin deficit in grams by multiplying pts. weight by the normal blood volume of 65mL/kg.Tis gives the total hemoglobin deficit.There are 3.3mg of iron for each gram of hemoglobin in the blood. So,lastly, multiply the total hemoglobin deficit by 3.3mg to calculate iron deficit. 


SOME FACTS ABOUT ORAL IRON REPLACEMENT

*The recommended daily dose for the treatment of IDA in adults is 150-200 mg per day of elemental iron.(a 325mg FeSo4 tablet has 65mg iron, a 325mg ferrous fumarate has 106mg of iron)
*It is best to give iron on an empty stomach ...as otherwise the iron binds with food in the stomach and impair
absorption; additionally, iron is best absorbed in an acidic environment.
*Since Iron is absorbed in the duodenum, enteric coated tablets may not be useful.
*After initiating oral iron, reticulocytosis will peak at 7-10 days in patients with moderate to severe anemia. *Hemoglobin levels begin to rise in 2 weeks. If taken in adequate doses, the hemoglobin would normalise by 8 - 10 weeks.
*10 to 20% of patients will have GI side effects. So, a tablet with lower elemental iron may be tried.....or tablet may be tried with a small snack(accepting a somewhat reduced absorption)

VRE ...when to treat!!

Vancomycin resistant enterococci are emerging as another leading nosocomial bacteria in hospitals.Enterococci are gram-positive and facultatively anaerobic microorganisms commonly found as part of the normal flora in the gastrointestinal tract.Several factors contribute to this increased risk among hospitalized patients, such as the disruption of the normal gastrointestinal flora by administration of broad-spectrum antibiotics, colonization with hospital-associated strains, poor infection control practices, presence of indwelling devices including urinary catheters, and an immunosuppressed state.Enterococcus faecalis andEnterococcus faecium are the two most common species isolated in this setting. The most common types of infection caused by enterococci are urinary tract infections (UTIs)


Given this intro...there may be 3 clinical scenarios we come across in hospital practice...
1. VRE UTI                 2. aymptomatic VRE bactereuria         3.VRE colonization
Well ..these have to be differentiated in clinical practice, as the last 2 dont need treatment , except in some special circumstances.

 A good detailed history about UTI symptoms in very much the deciding step for who to treat. Any lower or upper UTI system is needed to suspect UTI from VRE( except in elderly pts ). Once this is present, then proceed according to the flow sheet above.Evidence of VRE in the urine in the absence of symptoms or pyuria may have limited clinical importance in most patients, representing asymptomatic VRE bacteriuria or colonization, and generally does not require treatment; however, treatment may be considered in very high-risk patients (e.g., patients with catheter-acquired bacteriuria that persists 48 hrs after indwelling catheter removal, patients with planned genitourinary procedures, solid organ transplant recipients, neutropenic patients, and pregnant women).Always change Foley catheters once VRE is found in the urine.


 Aminopenicillins, both with (e.g., ampicillin-sulbactam, amoxicillin-clavulanate) or without β-lactamase inhibitors and penicillin are generally considered to be the drugs of choice for the empiric treatment of VRE infections.In case of ampicillin resistance , then nitrofurantoin or Linezolid can be used for VRE cystitis...........and Daptomycin or Linezolid can be used for upper tract UTIs and VRE bactermia. Duration of treatment doesnt need to be extended beyond 14 days.

The masks we (throw) use on patients .......

Oxygen masks are effective oxygen delivery device which is used mainly to supply oxygen from a storage tank to the lungs. Many people make use of this nowadays most especially medical care providers, aviators, medical researchers and hyperbaric chamber and other patients. Because of this, a wide variety of styles are now available for oxygen masks.

There are four available basic styles of oxygen masks. These are the simple facemask, the venture mask, the partial rebreather mask and the non-rebreather mask.

The simple facemask is the most commonly available oxygen mask to the public. This has a number of vents on both sides and can deliver 35-40 percent of oxygen. However if the oxygen flow increases to 10L/min, this can deliver up to 50 percent oxygen. The disadvantage with this type of oxygen mask is that this seals poorly and has large ventilation holes, thus oxygen flow is diluted with air.

The venture mask, on the other hand, is an oxygen mask that uses a mechanical venturi effect in order to increase the flow rate of oxygen into the mask. It supplies a desired amount of oxygen starting from 24% upto 40%, and this amount can be adjusted by using different valves. Useful in COPD patients when you want to control the amount of O2 they receive.

Another type of oxygen mask is the partial rebreather. This type of mask, which is often called as medium concentration oxygen delivery mask, almost looks like the non-rebreather mask but it does not have a one-way valve between the mask and the reservoir bag. This delivers almost 40 to 50 percent oxygen, and can increase up to 60 percent. Dont use this in a patient with tendency towards Co2 retention.

The last type is the non-rebreather. From the four types, this is the one that can deliver up to 90 percent of oxygen. This makes use of valves on both sides in order to prevent air and patient exhalation from diluting the oxygen in the reservoir bag. The valves open when the patient inhales and breathes in oxygen. However, masks of this type with valves on both sides are prescription masks only.

These are the different styles of oxygen masks. All are able to deliver the amount of oxygen needed. These are effective if used in appropriate clinical setting!!