ICU Rounds Report - Dec 16th, 2010

Auto-Anticoagulation of Cirrhosis? Patients with liver failure commonly present with elevated INRs and low platelet counts. Liver dysfunction alters synthesis and production of both the pro- and anti-coagulants produced by the liver. In addition, numerous other effects alter normal coagulation in the cirrhotic patient: low platelets, platelet dysfunction, altered endothelial function (including elevated levels of prothrombotic vWF and tFVIII), elevated levels of nitric oxide, etc. Further confusing things: liver failure can dramatically increase rates of fibrinolysis. What does it all mean?

In other words: Does a liver failure patient with an INR of 2.3 needs DVT prophylaxis?

It depends on who you ask. The recent medical literature suggests that cirrhosis offers little, or no protection.  Now, in the first study of its kind, researchers at the University of Missouri looked at the relationship between pathologic INR elevations and DVT. They retrospectively evaluated 190 hospitalized patients with varying degrees of chronic liver disease and found rates of DVT of 6.3% overall (by comparison, rates of DVT in high risk surgical inpatients without prophylaxis is between 4 - 8%).  Interestingly, higher elevations in INR were associated with greater DVT risk. Lastly, the study found that receiving DVT prophylaxis didn't protect against DVT, although the study was underpowered to detect a statistical difference and only 25% of liver failure patients received some kind of prophylaxis. Sadly, there is no data available for surgical patients.

What everyone can agree on is that current panel of test used to diagnosis coagulation abnormalities in liver failure (plt count, PT, aPTT) are worthless because the balance of pro/anticoagulant factors is not considered by these tests (which tend to measure simple deficiencies of anticoagulants). Abnormal hemostatic tests have never been shown to correlate to bleeding tendencies in liver failure. Further, it is clear from liver transplantation surgery that preemptive "correction" of the abnormal values does not reduce, and probably promotes, bleeding. With this shift in thinking, many centers are now reporting the ability to keep liver transplantation "bloodless" (no transfusions needed) greater than half the time. To accurately diagnosis whether a liver failure patient is pro- anti- or euthrombotic requires much more sensitive testing, such as TEG,  which is not widely available.

So we're left where we started, which is were every good paper ends: more research is needed! Do liver patients needs SCDs/heparin? Anyone's guess. How can we even measure coagulation in liver failure? Not really possible. Does prophylaxis even work in the setting of liver failure? No one has a clue. Is working in an ICU awesome anyway? Yes, very! 
Dabbagh, O, et al. Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest 2010; 137:1145.
Lisman, T, Porte, RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010; 116:878.
Gulley D et Al.  Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci . 2008; 53( 11): 3012- 3017.
Northup PG, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol 2006 ;101(7):1524-1528.

Gotta have more? Old Issues HERE.

ICU Rounds Report - Dec 9th, 2010

Creatinine, an oldie but a goodie? Creatinine is a breakdown product of creatine kinase in skeletal muscle. First found in blood in 1896, it was noticed that levels go way up with chronic kidney disease in the 1910's. We've been fixated on it every since as the biomarker for kidney function. It's been routinely measured on hospital inpatients for at least 60 years.  It's worth reviewing it strengths and weaknesses.

In the strength column, we can place that we have lots of experience with it. It's widely available, cheap to measure and tracks chronic disease quite nicely. Downsides? First, I've never liked saying it. It's a funny word. Second, the production of creatinine is highly variable, dependent on multiple factors including age, sex, race, muscle mass, nutritional state and others. Second, up to 40% of urinary creatinine is secreted by the tubules not filtered. In other words, it will never directly correlate with GFR as well as something that is not secreted at all, such as cysatinC (CysC). This leads to delays in the diagnosis of acute drops in GFR. Which brings us to the third major problem: It's slow. When the kidney filtering slows or stops, it takes days the serum creatinine to rise because basal production rates are so slow. Currently, we have to wait 2 days to learn the kidneys have been injured, beyond the time when interventions are thought to possibly improve outcomes. Its like trying to diagnosis an acute MI without troponins and just waiting to see how it will all settle out.

These limitations have lead to the intense development of serum and urinary biomarkers that better reflect GFR, give real time information about kidney injury and will, in all likelihood, make our old friend creatinine obsolete for ICU use with in 10 years . We've got several great candidates which work quicker, correlate better with disease severity and give more prognostic information coming down the pipeline, some of which are already being used in POC testing around the world (NGAL, KIM-1, L-FAB).
Rabinowitch IM. The prognostic value of the study of the blood creatinine in nephritis: based upon the study of fourteen cases with complete postmortem examination. Can Med Assoc J 1921; 11:320–322.
Moore, E, et al. Novel biomarkers of acute kidney injury: ready for clinical application? Current Opinion in Critical Care. Dec 2010 16(6): 523–525


Ultrasound for ICP. Occasionally, (meningitis, trauma, liver failure, strokes) we wonder what the pressure inside the head is. CTs of course, let us peek inside but only allow inferences. Sometimes, we wonder so much about ICP that we have the brain surgeons put an invasive monitor thru the skull. That's nice because it can also be therapeutic (in the case of EVDs). But is there a quicker way? Yes! Does it work? Maybe!

In 2010, when someone asks the question, 'is there a quicker way' the correct answer is either Epic or Ultrasound. Ultrasound? Sure. Recall that the optic nerve is sheathed within the dura. It appears that elevated pressures allow CSF buildup in this semi-compliant sheath and widen the diameter. (That's also the basis for blathering on about papilloedema). Multiple studies have measured the diameter of the optic sheath with ultrasound (at a standardized location, 3mm past the globe) and found a nice concordance with ICP. On study found a diameter greater than 5 (normal=3mm) was strongly predictive of an of ICP >20 mm Hg (sensitivity and specificity 94% and 76%, respectively).

Further work with MRI looking at the optic nerve sheath has shown that it is even more sensitive. With MRI, a cut-off value of 5.30 mm yields a sensitivity of 100% for diagnosis an ICP greater than 20.
Soldatos T. Optic nerve sonography: a new window for the non-invasive evaluation of intracranial pressure in brain injury. Emerg Med J  2009;26:630-634
Geeraerts T, et al. Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure. Crit Care 2008;12(5):R114. Epub 2008 Sep 11.

ICU Rounds Report - Dec 7th, 2010

It's so cold out there! Survival after out of hospital cardiac arrest with a good outcome is a rare event. Despite advances across other fronts in medicine, survival with an intact brain hadn't improved much in the last 50 years until someone tried post-arrest cooling. Previously, post-resuscitation efforts have been entirely supportive. Now, for comatose patients after vfib arrest, cooling the body to 34 degrees for 24 hours can nearly double the chance of recovery. Currently at UVa, we're cooling 3-4 patients a month (last month we did 7!).

But how do we cool patients? Everything has been tried. From ice bags, cold saline, irrigating bladder/stomach with cold fluids to cardiopulmonary bypass. All present technical and clinical challenges, not the least of which is that body vigorously defends its tightly regulated core temperature by increasing metabolic rate and shivering, usually requiring paralysis. Surface cooling is cumbersome and ineffective. Intravascular cooling (which we use) is expensive and risky. What if there was another way?

Researchers in toasty warm LA have published a trial using cannabanoid agonists in rats after resuscitation in vfib arrest. The results are very good news if you are a rat in a coma after vfib arrest: the drug appears to safely lower body temperature to ~34 degrees with no other major noted side effects. More importantly, the neurologic and functional outcome was significantly improved relative to controls.  The idea may represent a new therapeutic class for a common and lethal problem for thousands of Americans.

Finally, a quote from recent editorial on the new findings by Samuel Tisherman, "From the campaign 20 yrs ago (showing a frying pan representing marijuana and an egg representing your brain), to current controversies regarding legal medical uses, marijuana has a long history of capturing our interest. Wouldn't it be cool if a derivative actually improves brain function rather than frying it?"
Sun S, Tang W, Song F, et al: Pharmacologically induced hypothermia with cannabinoid receptor agonist WIN55, 212-2 after cardiopulmonary resuscitation. Crit Care Med 2010; 38:2282–2286
Bernard SA, Gray TW, Buist MD, et al: Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557–563