SIRS, Sepsis, + Septic shock

Question 1

The rationale for glucocorticoid administration in patients with sepsis and septic shock is based upon data which suggest that critical illness….

Answer 1

…induces a state of absolute or relative adrenal insufficiency that may contribute to shock.

Question 2

True or false:

For most adult patients with sepsis and septic shock, we suggest not routinely using intravenous glucocorticoid therapy as part of initial therapy.

Answer 2

True!

This approach is based upon randomized trials and meta-analyses that have consistently demonstrated that while glucocorticoid therapy leads to faster resolution of shock, there appears to be minimal or no effect on mortality.

Question 3

What is refractory shock?

Answer 3

A systolic blood pressure <90 mmHg for more than one hour following both adequate fluid resuscitation and vasopressor administration.

Question 4

When the decision is made to use glucocorticoid therapy in septic shock patients- what is the recommendation?

Answer 4

When the decision is made to use glucocorticoid therapy, we suggest hydrocortisone alone (<400 mg per day in divided doses) rather than combined therapy with fludrocortisone

Question 5

What is the recommended first choice vasopressor?

Answer 5

Norepinephrine is recommended as the first-choice vasopressor.

Vasopressin can be added to norepinephrine with the intent of raising MAP to target or decreasing norepinephrine dosage.

Question 6

What is procalcitonin?

Answer 6

A precursor to calcitonin

However, the synthesis of PCT can be increased (up to 100 to 1000 fold) as a result of endotoxins and/or cytokines

Question 7

What is CRP?

Answer 7

An acute phase protein that can increase with systemic infection

Question 8

What is significant about both procalcitonin and CRP in septic patients?

Answer 8

When we compared the combination matrix of CRP and PCT using the optimal cut-off values, the mortality rate of patients with elevated CRP and PCT was significantly higher than that of patients with non-elevated CRP and PCT or only elevated PCT. However, both CRP and PCT elevated was not an independent predictor of 28-day mortality.

Question 9

What is key in blood glucose management in sepsis patients?

Answer 9

A protocolized approach to blood glucose management which describes insulin infusion initiation when two consecutive blood glucose levels are > 180 mg/dL in ICU patients with severe sepsis is recommended.

This approach should target an upper blood glucose level < 180 mg/dL, rather than an upper target blood glucose ≤ 110 mg/dL.

Question 10

In ancillary analysis of data from the ALLHAT trial, _______ reduced the incidence of new-onset HFpEF compared with…

Answer 10

In ancillary analysis of data from the ALLHAT trial, chlorthalidone reduced the incidence of new-onset HFpEF compared with amlodipine, lisinopril, and doxazosin

Question 11

In HFpEF, what type of antihypertensives should one avoid?

Answer 11

Caveats include avoidance of excessive preload reduction. The patient who has LV diastolic dysfunction with a small, stiff LV chamber may be particularly susceptible to excessive preload reduction, which can lead to underfilling of the LV, a fall in cardiac output, and hypotension.

For these reasons, diuretics or venodilators such as nitrates and dihydropyridine calcium channel blockers must be administered with caution. Careful attention is required for symptoms of ventricular underfilling such as weakness, dizziness, near syncope, and syncope. Overdiuresis can also result in prerenal azotemia.

Question 12

Overdiuresis in those with HFpEF can result in…

Answer 12

Overdiuresis can also result in prerenal azotemia.

Question 13

Evidence of using MRA in HFpEF?

Answer 13

The TOPCAT trial randomly assigned 3445 patients with symptomatic HF and LVEF ≥45 percent to receive either spironolactone or placebo. The composite primary outcome (death from cardiovascular causes, aborted cardiac arrest, or hospitalization for HF) was lower, but not statistically different, with spironolactone compared to placebo (18.6 and 20.4 percent, respectively; hazard ratio [HR] 0.89, 95% CI 0.77-1.04). Hospitalization for HF was less frequent in the spironolactone group (12.0 percent) compared with the placebo group (14.2 percent; HR 0.83, 95% CI 0.69-0.99), but other components of the primary outcome occurred at similar rates in the two treatment groups. Total deaths and total hospitalizations were similar in spironolactone and placebo groups.

Question 14

ARB/ACE inhibitors in HFpEF?

Answer 14

There is no evidence from randomized clinical studies that ACE inhibitor therapy directly improves overall morbidity or mortality in patients with HFpEF. Because patients with HFpEF frequently have comorbidities such as renal insufficiency, ACE inhibitors should be used carefully to avoid the risk of renal dysfunction and hypotension.

There is no evidence from randomized clinical studies that ARB therapy directly improves overall morbidity or mortality in patients with HFpEF. There is no evidence of improved diastolic function with ARB treatment as compared with other therapies in patients with asymptomatic LV diastolic dysfunction or overt HFpEF

Question 15

What is the preferred treatment for those with HFpEF?

Answer 15

Mineralocorticoid receptor antagonists — For patients with clear evidence of HFpEF and current or recent (eg, within 60 days) elevated natriuretic peptide (either B-type natriuretic peptide [BNP] ≥100 pg/mL or N-terminal pro-BNP [NT-proBNP] ≥360 pg/mL) who can be carefully monitored for changes in serum potassium and renal function, we suggest treatment with an MRA.

Question 16

x

Answer 16

Acute phase proteins (APPs) are defined as proteins that change their serum concentration by >25% in response to inflammatory cytokines (IL-1, IL-6, TNFα). The acute-phase response is considered part of the innate immune system, and APPs play a role in mediating such systemic effects as fever, leukocytosis, increased cortisol, decreased thyroxine, decreased serum iron, and many others.

Question 17

CRP

Answer 17

Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via C1q.[5]

Question 18

x

Answer 18

When there is a stimulus, the CRP level can increase 10,000-fold from less than 50 μg/L to more than 500 mg/L. Its concentration can increase to 5 mg/L by 6 hours and peak at 48 hours. Therefore, the only factor that affects the blood CRP concentration is its production rate, which increases with inflammation, infection, trauma, necrosis, malignancy, and allergic reactions. Other inflammatory mediators that can increase CRP are TGF beta 1, and tumor necrosis factor alpha. In acute inflammation, CRP can increase as much as 50 to 100 mg/L within 4 to 6 hours in mild to moderate inflammation or an insult such as skin infection, cystitis, or bronchitis. It can double every 8 hours and reaches its peak at 36 to 50 hours following injury or inflammation. CRP between 100 and 500 mg/L is considered highly predictive of inflammation due to bacterial infection. Once inflammation subsides, CRP level falls quickly because of its relatively short half-life

Question 19

x

Answer 19

Scleroderma, polymyositis, and dermatomyositis elicit little or no CRP response. CRP levels also tend not to be elevated in SLE unless serositis or synovitis is present. Elevations of CRP in the absence of clinically significant inflammation can occur in kidney failure. CRP level is an independent risk factor for atherosclerotic disease. Patients with high CRP concentrations are more likely to develop stroke, myocardial infarction, and severe peripheral vascular disease.[44] Elevated level of CRP can also be observed in inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis.[26]

Question 20

x

Answer 20

C-reactive protein (CRP) is a traditional biomarker which is elevated in inflammatory states including rheumatoid arthritis and infection4. Aside from its roles as a biomarker, CRP also functions as a part of the defense mechanism against inflammation and pathogen invasion5. However, CRP has low specificity for diagnosing sepsis, and the plasma level of CRP is not a reliable indicator for the degree of systemic inflammation6.

PCT is used as an indicator for antibiotics treatment because the level of PCT is higher in fungal, parasitic, and bacterial infections than in viral infections. Accordingly, high early levels of PCT in sepsis have been suggested to be associated with unfavorable prognosis7. Nevertheless, early PCT levels are subject to alteration by the type and severity of the initial cause of the sepsis and not necessarily the severity of the sepsis itself; therefore, it is not recommended to utilize early PCT level as a definite indicator of prognosis

When we compared the combination matrix of CRP and PCT using the optimal cut-off values, the mortality rate of patients with elevated CRP and PCT was significantly higher than that of patients with non-elevated CRP and PCT or only elevated PCT. However, both CRP and PCT elevated was not an independent predictor of 28-day mortality.

Question 21

x

Answer 21

— The ESR, defined as the rate (expressed in mm/hour) at which erythrocytes suspended in plasma fall when placed in a vertical tube, is an indirect measure of the acute phase response and of levels of APR, particularly fibrinogen [6]. It can be influenced by other constituents of the blood, such as immunoglobulins, as well. The ESR can also be affected by changes that may be unrelated to inflammation, including changes in erythrocyte size, shape, and number; and by other technical factors.

Question 22

x

Answer 22

Systemic lupus erythematosus (SLE) represents an exception to the generalization that CRP concentrations correlate with the extent and severity of inflammation in patients with rheumatic disorders [75]. The ESR may be elevated, sometimes markedly, in patients with active SLE, while the CRP response is muted. The muted CRP response in SLE appears to result from the ability of type I interferons, which are highly expressed in most lupus patients, to inhibit CRP induction in hepatocytes [83]. While many patients with active SLE do not have significantly elevated CRP concentrations [84], CRP concentrations may be quite elevated in patients with active lupus serositis [85] or with chronic synovitis [86]. In a febrile lupus patient, marked CRP elevation (greater than 6 mg/dL) favors the diagnosis of bacterial infection [84]. In a landmark study, infection was present in all patients with CRP levels over 6 mg/dL (60 mg/L) except for those with serositis, supporting the clinical utility of regarding marked CRP elevation as strongly suggestive of infection [85]. (See “Clinical