Category Archives: Sepsis

Hyponatremia in SSTI

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I recently cared for a patient who was an injection drug user who presented with fever, tachycardia, and redness/swelling of the forearm near an injection site. Her initial workup was remarkable for an elevated white blood cell count, hyponatremia to the high 120s, and hyperlactatemia. The patient was not eager to be hospitalized (as I have found is often the case with patients who inject drugs), and during our conversation about the risks:benefits of hospitalization and aggressive treatment with IV antibiotics and supportive care for what I felt was likely a very serious soft tissue infection with sepsis, I mentioned that the patient’s blood level of sodium was low and that I was concerned this was a serious and grave sign that their infection might be quite severe. When I went home after the shift, I wondered what that was founded on other than knowing that sodium was included in the LRINEC score and having had some experience in the past seeing patients with serious / necrotizing skin/soft tissue infections (SSTIs) who presented with hyponatremia.

I did a brief literature search and turned up a few articles, including one publication from one of our program’s recent graduates looking at our county hospital’s population of IVDU-associated STTIs.

Briefly, what I found in these articles was:

a.) Hyponatremia is a commonly-reported finding in patients with skin and soft tissue infections, and it seems to be found more commonly in patients with IVDU-associated infections. It was found in 41% of the patients from the Detroit group, 38% of the San Francisco group (compared to 27% of non-IVDU patients), and in the study looking specifically at necrotizing infections (from UCLA Harbor, with 31% of the 124 patients reporting IVDU) 56% of the patients had hyponatremia.

b.) When present, hyponatremia seems to be related to worse outcomes and is prognostically generally a bad sign. The group from SFGH did not report the association between low sodium and outcomes, but the group from Detroit and UCLA both showed significantly higher mortality in the patients with low serum sodiums at presentation.

Another question I asked myself was why do these patients get hyponatremia? I don’t think anyone knows for sure, but the authors from UCLA Harbor postulated the following in their paper:

Sepsis leads to increased muscle glucose uptake, increased lactate production and decreased utilization, an increase in the calculated ratio of muscle membrane permeabilities to Na+ and K+, and an increased intracellular Na+ concentration. These effects may be mediated by complement activation. In addition, sepsis has been linked to an increase in antidiuretic hormone level as well as adrenocortical insufficiency, both of which may lead to hyponatremia. Finally, severe NSTIs lead to marked third spacing of fluids, which may be replaced by free water, leading to hypovolemic hyponatremia.

I don’t know for sure how all this translates into clinical practice, but I do pay attention when I see low sodium in patients with infection, particularly if I’m concerned about how aggressive of a soft tissue infection this might be. But I also know that hyponatremia can be caused by heart failure, dietary deficiency, water intake, drugs, all sorts of things. It is a laboratory finding associated with so many different underlying actual problems, making it rarely useful in isolation. I’ve seen this often used as the reason for justifying admissions for patients with vague symptoms and many comorbidities but I think it is rarely the isolated cause of all of what the patient is experiencing. It’s also something that’s intimidating to be tasked with correcting in people, given the apparent stakes we learn about in medical school! It would be interesting to learn more about hyponatremia acts as a prognostic indicator in all those other conditions — I’m sure it isn’t good.

References

Kievlan DR1, Gukasyan M1, Gesch J1, Rodriguez RM2. Clinical profile of injection drug users presenting to the ED. Am J Emerg Med. 2015 May;33(5):674-6. PMID: 25744147. [PubMed] [Read by QxMD]
Yaghoubian A1, de Virgilio C, Dauphine C, Lewis RJ, Lin M. Use of admission serum lactate and sodium levels to predict mortality in necrotizing soft-tissue infections. Arch Surg. 2007 Sep;142(9):840-6; discussion 844-6. PMID: 17875838. [PubMed] [Read by QxMD]

Transient Hypotension in the Emergency Department

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An interesting technicality in the use of the PERC rule to rule out pulmonary embolism is the tachycardia component — it asks not whether the patient is tachycardic at the time of the application of the rule, or whether tachycardia was sustained throughout the emergency department stay, but instead whether the patient had (as described by Jeff Kline in his great review article on PE diagnosis and risk stratification): “3. Pulse <100 beats/min during entire stay in ED”.  Meaning, even transient tachycardia may suggest a life-threatening diagnosis, even if it resolves while the patient is in the emergency department, and we’re probably PERCing out a whole bunch of patients inappropriately, at least according to Kline (who, notably, testifies a whole bunch as an expert witness in cases of missed pulmonary emboli).

I recently had a handful of patients in whom concerning blood pressures were measured and documented, which then resolved when vital signs were re-checked or after a small quantity of fluid or repositioning. I was wondering whether anyone had looked at the prognostic significance of ED hypotension, and whether these momentary dips in blood pressure should be something that concerns me. I did a quick search and found two studies that addressed this question in two different populations:

First we have, from the Rick Bukata school of title writing: “Emergency department hypotension predicts sudden unexpected in-hospital mortality: A prospective cohort study.”  This study, by Alan Jones and Jeff Kline out of (and formerly out of) Carolinas, prospectively enrolled 4,790 adult ED patients admitted to the hospital for reasons other than trauma. Patients were divided into those with and without systolic BPs below 100 mmHg at any time during their ED visit and followed through their hospitalization for the primary outcome of in-hospital mortality. Secondary outcomes included “sudden and unexpected death”, the relationship between the degree and the duration of hypotension measured and mortality, and the test characteristics of hypotension as a test for predicting in-hospital mortality.

Their conclusions are illustrated well in this graph:

hypotension

As they concisely summarize in the article’s conclusion:

Patients exposed to hypotension had a threefold increased risk of in-hospital death and a 10-fold increased risk of sudden, unexpected in-hospital death. Patients with any one SBP < 80 mm Hg had a sixfold-increased incidence of in-hospital death, and patients with a SBP < 100 mm Hg for > 60 min had almost a threefold-increased incidence of in-hospital death.

The second article from the same group echoes this conclusion in a different population of patients. This article, “The significance of non-sustained hypotension in emergency department patients with sepsis” is a secondary analysis of the above data set which looks specifically at the prognostic value of non-sustained hypotension defined as one or more occurrence of SBP < 100 mmHg in patients with sepsis as defined by the receipt of antibiotics in the ED + at least two SIRS criteria.

774 patients met their inclusion criteria for sepsis, and after 74 were excluded for “overt shock” (sustained hypotension or use of pressors). They examined the remaining patients for a primary outcome of in-hospital death.  They found, as one might expect, that hypotension predicts worse outcomes in this sub-population of patients — including when patients had non-sustained hypotension. Again, there seemed to be a “dose-dependent” relationship, with an inverse relationship between the nadir of the ED SBP and the frequency of in-hospital death, as shown here:

sepsishypotension

Another important finding (though taken in context of a fairly small sample) was the statistically similar incidence of the primary outcome in both the groups with transient and sustained hypotension. Both groups of patients had a 2.5-3x higher risk of in-hospital mortality when compared to patients without any hypotension.

Without belaboring the point, these two studies underscore the prognostic significance of even transient hypotension in the undifferentiated emergency department patient, and (as is better known to have implications in terms of severity) in patients diagnosed with sepsis. Like the previous post regarding lactate, or the well-known pearl about tachycardia at discharge, this is a number that should get your attention and which demands evaluation and possible intervention / escalation of care.

References

Marchick MR1, Kline JA, Jones AE. The significance of non-sustained hypotension in emergency department patients with sepsis. Intensive Care Med. 2009 Jul;35(7):1261-4. PMID: 19238354. [PubMed] [Read by QxMD]
Holler JG1, Bech CN1, Henriksen DP2, Mikkelsen S3, Pedersen C4, Lassen AT1. Nontraumatic hypotension and shock in the emergency department and the prehospital setting, prevalence, etiology, and mortality: a systematic review. PLoS One. 2015 Mar 19;10(3):e0119331. PMID: 25789927. [PubMed] [Read by QxMD]

Hyperlactatemia in the Emergency Department

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Much has been made over measurement of serum lactate over the last several years– primarily focusing on whether we should be measuring it in the first place, and what the significance (and etiology) of elevations in serum lactate is, and what role it should play in diagnosis and risk stratification. Back in 2010, Scott Weingert was organizing the New York Sepsis Collaborative, and produced this podcast covering the basics of lactate measurement, with a particular bent towards sepsis. He did a great job covering the essential take-home of the data that existed thus far, and addressed a lot of points of confusion many people have about lactate — namely, the idea that it results from hypoxia/hypoxemia or anaerobic respiration, and covers some of the alternative etiologies of hyperlactatemia, i.e. any beta agonist, whether endogenous catecholamines or exogenous, such as albuterol or epinephrine being used as a vasopressor. The takeaway from this, echoed in sepsis care guidelines issued by many other organizations since and in the policies and protocols in many hospitals and emergency departments, is that elevated lactate is a marker of increased mortality, and may be an early alarm that someone is in septic shock or headed towards it.

I wanted to cover two studies — one by Shapiro et al. (a big name in sepsis research), and the other by del Portal et al– that looked at this question in the ED. These were prospective and retrospective cohort studies respectively, and both looked at over 1,000 emergency department patients and evaluated the prognostic significance of elevated venous lactate measurements. In the first study by Shapiro et al, they evaluated all patients admitted to the hospital with an infection-related diagnosis. In the second study, they looked at older adults admitted to the hospital with any diagnosis, though a very large proportion of patients were excluded. Reasons for exclusion (they excluded >14,000 of 16,886 total admissions , so I think this really affects the robustness of this paper) were things like being a sick trauma patient, transfers out, LWBS or leaving AMA — those are all reasonable, but they also excluded all patients in whom a lactate was not drawn in the ED. Without providing the numbers to break this down, it’s tough to say how generalizable these conclusions are, or if lactates were only obtained in patients that the providers thought were sick/potentially septic in the first place (which was the protocol at the hospital conducting the study by Shapiro et al.).

As one might expect, both studies found that hyperlactatemia correlates with badness in the form of increased mortality. The relationship is linear, and statistically significant. The authors also stratified the mortality by time — in Shapiro et al. by 28d in-hospital v. death within 3 days (top graph), and in del Portal’s study by in-hospital, 30 day and 60 day mortality (bottom):

lactateshapirolactatedelcar

Note the similar trend and the steep upward trajectory of the relationship — these results have been paralleled in the critical care literature, and have led to the commonly-accepted idea that a lactate > 4.0 is a threshold above which one should be concerned for hypoperfusion or shock, even in the absence of hypotension. These studies do not, and no studies have, established a causal relationship between lactate elevation and increased mortality– nor have they shown that trying to “clear” lactate will lead to better outcomes than trending alternative markers of perfusion (though several studies have looked at this question, without any definite conclusions). They also did not establish that one need only be worried about lactate > 4.0 — multiple studies including this one have shown that infected patients with lactate in the 2.0–3.9 mmol ⁄ L range have a risk of mortality that is approximately twice that of patients with a lactate level of < 2.0 mmol ⁄ L. They also have not established that we need not be worried about patients without hyperlactatemia — so-called “occult” sepsis.

More recent studies have questioned the relationship between hyperlactatemia and hypoperfusion per se by looking at changes in microcirculation, but I think it’s safe to say that an elevated lactate in a patient with suspected infection should still ring alarm bells in your head. Having these mortality “buckets” in mind when mentally risk stratifying patients or prioritizing them for workup or interventions can also help — particularly when these patients might otherwise look well and thereby fly under the radar.

In my mind, an elevated serum lactate must be explained — sometimes, the explanation is that they just got a nebulizer treatment, are in alcoholic ketoacidosis (which along with the production of ketones, leads to an accumulation in reduced nicotinamide adenine dinucleotide (NADH), which then results in impaired conversion of lactate to pyruvate or preferential conversion of pyruvate to lactate, both resulting in increased lactic acid level), or seized. But these are diagnoses of exclusion, and one must assume until proven otherwise that this represents their body’s sympathetic accelerator pedal being pushed to the floor and that they are needing resuscitation and provision of care with the mentality that this is a sick patient.

 

References

Shapiro NI1, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, Weiss JW. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005 May;45(5):524-8. PMID: 15855951. [PubMed] [Read by QxMD]
del Portal DA1, Shofer F, Mikkelsen ME, Dorsey PJ Jr, Gaieski DF, Goyal M, Synnestvedt M, Weiner MG, Pines JM. Emergency department lactate is associated with mortality in older adults admitted with and without infections. Acad Emerg Med. 2010 Mar;17(3):260-8. PMID: 20370758. [PubMed] [Read by QxMD]