Critical Care, Improving Outcomes, Mythbusting

Procalcitonin: Holy Grail, or Holy Sh*t ?

Procalcitonin is marketed as, “a marker of broad routine use, both for differential diagnosis of bacterial infection as well as for antibiotic stewardship.

But is it?  This study looks at 107 ICUs that had >25 sepsis cases in 2012, and had an ability to perform procalcitonin (PCT) levels on their septic patients, and essentially looked to compare the outcomes of those that had PCT ordered and those that did not.  All in all, there were about 17,000 septic patients without a PCT ordered, and about 3800 patients with a slightly lighter wallet and slightly more anemic after their admission than their comparators.

There was little difference in baseline characteristics – save for those having PCT ordered more likely hailing from the West (27.9% of PCT orders vs 12.7% of those not getting PCT ordered) and the opposite holding true for the South (55.3% without vs 49% with PCT).  PCT was slightly less ordered at teaching facilities (37.8% of septic patients without PCT orders vs 31.9% of those with a PCT ordered).  All other OR were <1.25.

There was no difference in length of stay and no differences in mortality.

There was an increase in days of antibiotic treatment for those in whom a PCT was ordered (relative risk increase 1.17), and with that an accompanying increase in Cdiff (OR 1.42) .  Of course, 1 PCT begets another (33% of the time, and about 3 days later).  Patients with serial PCT orders had higher rates of antibiotic use, higher Cdiff, and again, no mortality benefit.

Stop the madness.  Indiscriminately ordering tests that will not change management should not be done.  And they certainly should not be repeated.

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Critical Care

Who ya gonna call? #VancZosyn!

If there’s some strange cough in your resus room,

Who you gonna call? Vanc-ZoSyn!
If something’s fevered… and it don’t look good,
Who you gonna call? Vanc-ZoSyn!

I ain’t afraid of no Staph.
I ain’t afraid of no Strep.

If high lactates are running through your EMR,
Who you gonna call? Vanc-ZoSyn!

 

There’s been some FOAM rumblings about Vanc/ZoSyn causing AKI, but this was the first time it has been compared directly head to head with Vancomycin-Cefepime. This was a retrospective matched cohort study with 279 patients in each arm – one received combination therapy with vancomycin-cefepime (VC), the other received vancomycin-piptazobactam (VPT) for > 48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dl or they were receiving RRT. Patients receiving VC were matched to patients receiving VPT based on severity of illness, ICU status, duration of combination therapy, vancomycin dose and number of concomitant nephrotoxins. The primary outcome was the incidence of RIFLE criteria-defined AKI, with a slew of secondary outcomes performed as well.

So, wait, what’s so special about RIFLE anyway? Glad you asked: In general, the worse the acute kidney injury, the higher the mortality.

Since this study shows an 11% AKI rate with VC and 29% AKI rate with VPT, maybe we can improve our mortality if we simply switch from zosyn to cefepime?

Except that this group reports mortality was actually worse in the VC group (though not statistically significant – 8.6% vs 5.7%). That’s right – the group with more AKI had less mortality. In other news, ICU stay was decreased (6 vs 8 days), which was statistically significant., and only ~1% of patients in both arms required long term hemodialysis.

While I was getting ready to click submit on this blog post, I found a second paper (published Nov 28, 2016) that looked at a matched cohort of 1633 VPT vs 578 VC patients, with essentially similar results – 21.4% AKI in VPT vs 12.5% VC.  This second paper found similar LoS, but also a similar trend in mortality-  6.9% for the VPT arm and 9.2 for VC.

So… I’m not certain what to make of this – but it seems more than fair to question whether drug induced AKI is a meaningful surrogate marker for sepsis mortality.  We need a long term look at mortality between VC vs VPT to see if VPT induced AKI follows the same trends. Maybe we’re trading a slight bump short term mortality for improved long term mortality with VC (or maybe not).  In the meantime, I think we need to pump the brakes on shouting about Vanc/Zosyn AKI until we sort this out a bit more.

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Critical Care, Improving Outcomes, Mythbusting, Neurology

Compazine… for infectious disease?

Today’s article’s (1, 23 ) are a break from the usual trials that are typically discussed and a bit more “benchside medicine” than bedside medicine.  In fact, let’s look at this as an early request for one of the 12 trials of Christmas.

Phenothiazines have demonstrated in vitro (as well as some in vivo) activity for gram positive cocci, mycobacteria, amoeba (4; 5), and some gram negative rods.

It should be noted that Klebsiellae, pseudomonads and acenetobacters were highly resistant to almost all of these drugs.

The MIC for phenothiazines are usually not reached with conventionally used doses, but these compounds do enhance the activity of various antibiotics to which various bacteria are susceptible (including vancomycin), and even decrease the MIC of resistant organisms.

So where am I going with all of this? For starters, lets look at some common causes of meningitis, in no specific order:

Strep pneumo (gram positive); group B strep (gram positive); staph aureus (gram positive); Listeria (gram positive); Neisseria meningitidis (gram neg diplococci); H flu (gram neg)

All things phenothiazines are thought to have activity against.

You’re likely to be giving patients with potential meningitis something for pain (I hope?), so why not go with compazine?  Likewise, patients whom you may suspect bacteremia from a cellulitis, why not give compazine to, ummm, “counteract the nausea” associated with the opiates you gave for pain control?

I think this falls into the unlikely to harm, might help category, and is seemingly a ripe area for research.  Is this practice changing?  Nope, not at all.  Food for thought, but until compazine is proven unsafe in an infectious process, I will continue my love affair with compazine for headaches, nausea, and vomiting (regardless of suspected etiology).

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Critical Care, Improving Outcomes, Mythbusting

1 in 10 EGLS saves a life.

Do current sepsis guidelines go far enough?

That was my first thought when I read today’s article. This single center ICU study looked at 220 patients divided into two categories- one category in which patients that were managed in adherence with the 2012 surviving sepsis guidelines – 20-49 ml / kg initial IV fluid bolus, continued fluid challenges until CVP of 8-12, with more given based on treating team. Noradrenaline until MAP of 65, and dobutamine for cvSO2 <70% in combination with either lactate >2 or urine output <0.5 ml / kg / hr). The other 110 patients had treatment guided by limited echo:

Treatment options looked like this:

1) IVC fluctuation <15% & normal LV function= give pressors only (discontinue IV fluid)

2) IVC fluctuation >15% & normal LV function = 20-40 ml /kg IV fluid given

3) IVC fluctuation >15% & mod/severe LV function = 10-20ml/kg IV fluid given AND initiate dobutamine 5ug/kg/min

4) IVC fluctuation <15% & mod/severe LV function = discontinue IV fluid and initiate dobutamine 5 ug/kg/min

 

These patients were pretty sick- all patients were mechanically ventilated and on noradrenaline. Limited echo was performed within 24 hours of presentation to ICU and within 36 hours of presentation to the ED (actual times were within 7-15 hours in the ICU, on average, 11 hours). Patient characteristics were pretty similar in terms of age, APACHE scores, and labs (similar ESRD/CHF percentage as well ~20% of both patient arms). Surprisingly, patients received a ridiculous amount of IV fluid from the ED – 68 (55-70) ml / kg in the echo group vs 65 (55-72) ml / kg in the standard of care arm. Yes, even with 20% of patients having ESRD / CHF – the least amount of IVF given was 55 ml / kg !

Results?

Despite all of this IV fluid given in the ED, 35% of patients still have >15% IVC collapse (!). 65% of patients had their fluid restricted, and 22% in the echo arm vs 12% in the standard of care were started on dobutamine. On Day 1 in the ICU, patients received less IVF in the echo arm (49 (33-74) ml / kg, vs 66 (42=100) ml / kg) – but still a significant amount if IVF.

28 day survival was 56% vs 66% in favor of the echo arm, with significantly less acute kidney injury (65% vs 88% for all AKI, and 19% vs 36% for stage 3 AKI).

So your NNT to save a life is 10, and 4 to reduce incidence of any AKI.

So, is this really an ED paper? Well, it depends on your area of practice. The local flavor of the authors is such that their local policy was to initiate dobutamine in the ICU and not in the ED. Are you boarding ICU players? Are your hospitalists ultrasono savvy? How involved are your intensivists in patient care while patients are awaiting an ICU bed? Are you okay with administering at least 40 ml /kg IV fluid and starting pressors on your septic shock patients? If the answer is no or “not really” to any of these questions, then the answer is yes.

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Improving Outcomes, Improving Throughput, Mythbusting

Albuterol: Sepsis Mimic

In today’s day and age of overtesting, some providers will not send home a patient with an abnormal lactic acid at all, regardless of etiology. So let’s examine what can possibly cause abnormalities of the current apple of our sepsis eye.

Here, 28 healthy subjects were randomized to placebo or 10 mg of nebulized albuterol over an hour. This is what many of us would consider “an hour long treatment” – or about 4 of those plastic neb vials. Serum lactate (and serum potassium as well) was measured prior to treatment, and at 30 minutes and 70 minutes after the start of treatment.

In the 14 patients receiving albuterol, their lactate went up on average 0.77 mmol/L vs a decrease of 0.15 mmol/L for the placebo group, while serum potassium levels went down by 0.5 mEq/L in the treatment arm vs no change in the placebo arm.

In our current overdiagnosis induced sepsis frenzy, if you must order a lactic acid, do it before giving albuterol, or better yet, if there is clearly some other reason for dyspnea aside from an infectious etiology (asthma or COPD that require immediate albuterol) – don’t order a lactic at all and document that an infectious etiology is not the cause of today’s abnormal vital signs.

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