Lisa Sanders hits another home run – Losing Consciousness.

Those who enjoy hearing about rare syndromes will enjoy this one – I sure did.

Tolvaptan is an ADH antagonist.  We will have few indications, but in the rare true SIADH patient, this drug will have some value.  I do not know the cost.

I see many hyponatremia patients, and few of them have persistent SIADH.  I am glad to have this option for those rare patients. 

The NEJM had a couple of important articles about tolvaptan a couple of years ago.

Making rounds yesterday in the ICU, we found this electrolyte panel

Clinical context – 50 year old woman with known cirrhosis and gram negative sepsis.  Her creatinine and BUN are improving with volume expansion. 

I asked readers to explain her decreased HCO₃

Let me add that she was intubated and on a respirator.

I thank the readers for falling for my trap.  I have posted cases like this in the past, but this may be a better example. 

You cannot make an acid-base diagnosis without an arterial blood gas.

On FiO₂ 30%

The decreased bicarbonate is appropriate for the degree of hyperventilation.  The patient had a respiratory alkalosis with appropriate metabolic compensation.

Our strategy was to decrease the ventilator rate.

Major teaching point here – pCO₂ is a pure measure of ventilation.  As a 4th year medical student, one of our favorite teachers – Dr. Orhan Muren – said this 100 times if he said it once.  By definition the decreased pCO₂ equates with hyperventilation.

Making rounds today in the ICU, we found this electrolyte panel

Clinical context – 50 year old woman with known cirrhosis and gram negative sepsis.  Her creatinine and BUN are improving with volume expansion. 

Explain her decreased HCO₃

Most readers know that I run morning report 2-3 times each week (at 3 different hospitals.)  We frequently discuss the rationale for statin therapy.  Many students and residents focus on LDL and LDL goals, yet recent data suggest that statins really work in at least 2 ways.  Clearly, statins do lower LDL, and thus probably either decrease atherosclerotic plaques or delay their growth.  However, statins also decrease the ongoing inflammatory process within the atherosclerotic plaque.  This plaque stabilization should decrease cardiac events.

We know that immediate statin treatment improves myocardial infarction outcomes.  We believe that this effect stems from a marked decrease in subsequent infarctions.

Recent data are raising questions about our selection criteria for statins.  All experts agree that statins have important effectiveness as secondary prevention.  Data suggest that all patients with proven atherosclerosis benefit from statins, regardless of their initial LDL.  Recent data argue that treating patients with elevated CRP levels might make sense in primary prevention.

This rather long article discusses the data – The Goal of Statin Therapy: LDL? CRP? JUPITER Study

Talking about the Jupiter trial:

Dr. Gotto: What lead to the development of this trial was a post hoc analysis that Dr. Ridker and I and colleagues did on the AFCAPS/TEXCAPS Study.[4] It was a primary prevention trial in people who at that time had what were considered normal lipids except they had a below average HDL. Lovastatin reduced events by 37%. In post hoc analysis, if you had above the median LDL and CRP, you benefited. If you had above the median of either one with the other one below the median, you benefited. The only group that did not benefit were those who had a low LDL and a low CRP — low being below the median — and that group was not tested in this present trial.

The potential synergism of LDL and CRP reduction:

Dr. Willerson: To be complete, also in the New England Journal of Medicine, Steve Nissen and his associates at the Cleveland Clinic did a separate study.[5] They were using ultrasound looking at coronary arteries, looking at reductions in LDL and CRP. They showed exactly the same thing. If you reduced LDL, you got a certain stability of progression of atherosclerosis. If you reduce CRP, you get a certain stability. But if you reduce both, you got an additive stability of coronary atherosclerosis.

So what is my current take?  Secondary prevention is not controversial; primary prevention is very controversial.  I would divide the primary prevention candidates into overall low risk and moderate to high risk.  Those at moderate to high risk represent the real controversy.  The CRP data have caught my eye.  I suspect that measuring CRP in patients with other factors raising risk might make sense.  Fortunately, several excellent statins are generic.  If I had CAD risk factors (my only personal risk is my Y chromosome), I would probably take a statin.  Of course, I take no medications, enjoy taking no medications, and have a desire to continue taking no medications, so I do not know what I would really do.

Statins are not totally benign, but clearly for secondary prevention the risk benefit ratio is tilted strongly to the benefit side.  We still do not have solid answers on primary prevention, but in my mind the data are building towards treating patients with both elevated LDL and CRP.

Earlier this week I received an email asking my opinion of an ER sore throat policy.  The question focused on acute rheumatic disease prevention, and ask my opinion on testing and treatment.  Here is my short answer:

This is a classic question.  I will provide a fairly long answer.

I know of 5 reasons to treat sore throats.  Each deserves some discussion.
 

1. Prevent rheumatic fever.  In North America this rationale is no longer important.  We have very little rheumatic fever, and your estimates seem rational. We see no major difference in this rare complication regardless of strategy.
2. Prevent suppurative complications.  Antibiotics do decrease the incidence of peritonsillar abscess – quoting from Cochrane: “Antibiotics reduced the incidence of acute otitis media (RR 0.30; 95% CI 0.15 to 0.58); of acute sinusitis (RR 0.48; 95% CI 0.08 to 2.76); and of quinsy (peritonsillar abscess) compared to those taking placebo (RR 0.15; 95% CI 0.05 to 0.47).”
3. Shorten duration of symptoms – clearly when adult patients have group A strep they have symptom resolution faster, especially when their symptoms are more severe
4. Decrease spread to close contacts – antibiotics markedly reduce transmission
5. Prevent death – the very rare patient with strep will suffer streptococcal shock syndrome – probably not a reason to consider antibiotics

Experts greatly disagree on these issues and their relative importance.  I treat sick pharyngitis patients knowing that I decrease the risk of suppurative complications (although we do not eliminate that risk) and to decrease the duration of their illness.
 

An underpinning of this "controversy" involves an understanding of the microbiology of tonsillitis and pharyngitis.  Most physicians (including many experts) only worry about Group A strep.  As readers know I worry about the common non-group A strep – Group C and Group G.  Obviously, I am also quite worried about Fusobacterium necrophorum. While rare, Neiserria gonorrheae can cause suppurative pharyngitis. 

Other important considerations in the differential include acute HIV infection, EBV, chlamydia and mycoplasma.  Finally, we must always think about the initial presentation of suppurative disease (especially peritonsillar abscess.)

The problem with adult sore throats is that most physicians consider them simple, routine and uninteresting.  In fact, the management of most pharyngitis is simple and routine, but just because most patients have a viral infection or strep throat does not mean we should not think carefully about each patient.  We have a responsibility to understand the red flags for even this seemingly routine problem.

The primary care physician drew blood cultures and started moxifloxacin.  Two days later the blood cultures come back growing gram negative rods in the anaerobic bottles.  He is called back to the ER.  On exam he has a fever of 103, markedly swollen right tonsil with exudates, mild swelling of right neck, but no clear adenopathy.  He does not have a cough.

CT scan shows a huge right tonsil, but no evidence of abscess and normal patent internal jugular vein.

Now what would you do?

What do you think is wrong with this man?

A 30-year-old man comes to your office for 2 days of progressive pharyngitis.  He is unable to eat but is drinking well.  He has a temp of 103 and endorses a drenching night sweat.  He has a swollen right tonsil with marked exudates.  His right neck is slightly swollen.  You cannot feel anterior or posterior adenopathy.

His rapid strep test and flu screen are both negative.

Would you give antibiotics?

Would you get blood cultures?

I am current at the ACP annual meeting, and this morning heard a brilliant grand rounds on hyponatremia – given by Juan Carlos Ayus.  I have found an excellent article in the Southern Medical Journal that he co-authored on treatment of dysnatremias and also provide this Medscape link – Hospital-Acquired Hyponatremia — Why Are Hypotonic Parenteral Fluids Still Being Used?

Hospital-acquired hyponatremia can be lethal. There have been multiple reports of death or permanent neurological impairment in both children and adults. The main factor contributing to the development of hospital-acquired hyponatremia is routine use of hypotonic fluids in patients in whom the excretion of free water, which is retained in response to excess arginine vasopressin (AVP), might be impaired. The practice of administering hypotonic parental fluids was established over 50 years ago, before recognition of the fact that there are numerous potential stimuli for AVP production in most hospitalized patients. Virtually all neurological morbidity resulting from hospital-acquired hyponatremia has been associated with administration of hypotonic fluids. Multiple prospective studies have shown that 0.9% NaCl is effective prophylaxis against hyponatremia. There is not a single report in the literature of neurological complications resulting from the use of 0.9% NaCl in non-neurosurgical patients. Patients at greatest risk of developing hyponatremic encephalopathy following hypotonic fluid administration are children, premenopausal females, postoperative patients, and those with brain injury or infection, pulmonary disease or hypoxemia. When hyponatremic encephalopathy develops, immediate administration of 3% NaCl is essential. In this Review, we discuss the question of why administering hypotonic fluids is unphysiologic and potentially dangerous, the settings in which isotonic fluids should be administered to prevent hyponatremia, and the appropriate treatment of hyponatremic encephalopathy.

Several key points that added to my knowledge:

1. Premenopausal women are more likely to develop hyponatremic encephalopathy – probably secondary to the effect of estrogen on astrocytes – therefore increased cerebral edema for the same level of hyponatremia

2. The cerebral edema can cause non-cardiogenic pulmonary edema – and thus hypoxemia.

3. When hypoxemia occurs, then cerebral blood flow decreases, with potential disastrous results.

4. He argues passionately against the routine use of hypotonic parenteral fluids (see the link above)

5. He argues that the treatment for hyponatremic encephalopathy is 100 cc of hypertonic saline (3%) push, with transfer to the ICU and careful frequent monitoring of sodium levels.  Pulmonary edema is not a contraindication to hypertonic saline if the patient has normal heart size.

This was truly an excellent talk on an infrequent but potentially lethal condition.  He included in the discussion the consideration of marathon runners.  He now recommends that marathon runners to present with altered mental status should receive 100 cc of 3%NS bolus.  According to his presentation this can save lives.  The articles address the risk of demyelinization – and explain how to avoid that complication. 

Activated Vitamin D Associated with Mortality Drop in Chronic Kidney Disease

For patients with moderate-to-severe chronic kidney disease and hyperparathyroidism, activated vitamin D appears to lower the risk of death over two years, an observational study found.

The 429 patients with stage 3 or 4 disease who took oral calcitriol had a 26% reduced risk of death (P=0.016) and a 20% reduced risk of death or long-term dialysis (P=0.038) compared with 989 patients who did not take oral calcitriol, Bryan Kestenbaum, M.D., of the University of Washington here, and colleagues reported online in the Journal of the American Society of Nephrology. The results will be published in the August print issue.

These data have great importance to generalists and nephrologists.  These data support the hypothesis that the secondary hyperparathyroidism Is a major problem for these patients.