Pathophysiology of Sepsis

My learning materials developed for first year postgraduate emergency medicine candidates on the concept in the pathophysiology of sepsis using storify.com.

Pathophysiology of sepsis

Below are my notes prepared for the intensive course revision for the year 1 emergency medicine postgraduate trainees.

Sepsis from Chew Keng Sheng

Etomidate Versus.....

Widely used as an induction agent, etomidate is an ideal agent for emergency endotracheal intubation because:

1. of its predictability in dosing
2. reliable hypnotic effect
3. rapid onset
4. short duration of action
   
5. it has no effect on histamine release, which contributes to its hemodynamic stability.

Unfortunately, since the early 1980s, there has been concerns about the use of etomidate in critically ill sepsis patients because of its adrenal suppression effects resulting in adrenal insufficiency.

Nonetheless, Journal Watch recently publishes a commentary on a study comparing the effects of etomidate versus midazolam. In fact, a further search shows that there has been another comparison study between etomidate versus ketamine. In both of these studies, when put under comparison, etomidate does not demonstrate significant increase in terms of serious adverse effects.

1. Etomidate versus Midazolam

In this prospective, double-blind, randomized trial involving 122 adult patients in a single emergency department with suspected sepsis and indicated for intubation, the patients were randomized to either receivemidazolam (0.1 mg/kg) or etomidate (0.3 mg/kg) for induction.

No significant differences were demonstrated (midazolam vs etomidate) in terms of

• median hospital length of stay (9.5 and 7.3 days)
• median intensive care unit LOS (4.2 and 3.1 days)
• median ventilator days (2.8 and 2.1 days), or
• inhospital mortality (21% and 26%).

A further subgroup analysis of patients who survived to discharge also showed no difference in median hospital LOS between midazolam and etomidate recipients (11.3 and 11.8 days).

Reference:
Tekwani KL et al. A comparison of the effects of etomidate and midazolam on hospital length of stay in patients with suspected sepsis: A prospective, randomized study. Ann Emerg Med 2010 Nov; 56:481. (Abstract)

2. Etomidate versus ketamine

In another prospective trial involving 469 critically ill patients, the patients were randomized to either receive a single intravenous bolus of etomidate (0.3 mg/kg) or ketamine (2.0 mg/kg) for induction. Unlike the other study mentioned, this study involves 65 intensive care units (ICUs) and 12 emergency departments or prehospital systems in France.

And the results are: yes, adrenal insufficiency did indeed occur significantly more among etomidate recipients compared to ketamine recipients (86% vs. 48%; odds ratio, 6.7).

However, in terms of serious adverse events (maximum sequential organ failure assessment (SOFA) scores during the first 3 days in the ICU, or 28-day mortality, etc), again there was no significant differences were noted between groups.

Reference:
Jabre P et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: A multicentre randomised controlled trial. Lancet 2009 Jul 1; click here.

In other words, although etomidate use does show an increase risk of adrenal insufficiency, a single bolus dose of etomidate does not seem to have increased risk of adverse events when compared with other agents. I am awaiting for more studies in this area..........

Necrotizing Fasciitis

Necrotizing Fasciitis can potentially be a life-threatening and limb-threatening bacterial soft tissue infection. Although it is commonly polymicrobial, one of the notorious organism is Group A Beta Hemolytic Streptococcus (GABHS). The organisms are commonly anaerobic types as these organisms thrive well under the local tissue hypoxia environment although the anaerobic organisms can co-exist with the aerobic types.

Unbeknownst to the patient, often the organism enters the subcutaneous tissue due to very trivial trauma. Nonetheless, as expected, there will be certain predisposing factors which render the host to be immunocompromised for such severe soft tissue infection to occur; viz, diabetes mellitus.

To differentiate necrotizing fasciitis which may rapidly lead to fulminant sepsis and septic shock from cellulitis, one of the key clinical feature of necrotizing fasciitis is that:

the pain and tenderness that the patient experiences may be "out of proportion" to the visible skin lesion externally (in fact, the overlying skin changes are often milder compared to the degree of necrosis occurring underneath).

Secondly, some patients with necrotizing fasciitis may have subcutaneous emphysema which probably is not present in simple cellulitis.

Thirdly, from the external look as well, the picture of necrotizing fasciitis just appear "uglier" with bullous lesions with serous discharge (as in the picture above).

Pathologically, in necrotizing fasciitis, the organisms are notoriously aggressive by invading the underlying fascia (thus the name, fasciitis). This also earns them the title "flesh eating bacteria syndrome". In contrast, in simple cellulitis, the organisms seldom go beyond the underlying fascia, although, if left untreated, necrotizing fasciitis is a sequelae of cellulitis.

Read an article from e-Medicine online here.

Download a FREE BMJ Review article on necrotizing fasciitis here.
Download another excellent FREE review article here.

Note: kindly report any broken link to cksheng74@yahoo.com

© 2010 by Dr. Keng Sheng CHEW.


Necrotizing Fasciitis by Dr. Keng Sheng CHEW is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

Will Procalcitonin Become An Indispensable Diagnostic Tool To Guide Antibiotics Use in Respiratory Infections? A Step Closer Towards The Reality

From the results of a multicenter, randomized controlled trial reported in the September 9 issue of the Journal of the American Medical Association (JAMA), it seems probable that Procalcitonin (PCT) measurements may reduce rates of antibiotic use for lower respiratory tract infections (LRTIs).

Although procalcitonin is not routinely used in clinical practice in Malaysia, certainly as more and more data are available in the future, it may become an important diagnostic and prognostic adjunct.

Inappropriate antibiotic prescribing for lower respiratory tract infection (LRTI) is widespread and can promote bacterial resistance while increasing costs and incidence of drug-related adverse effects.

In that study, Schuetz P et al. from the ProHOSP Study Group, evaluated whether the use of a serum procalcitonin (PCT)-based algorithm could safely reduce antibiotic administration for LRTI (defined as community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, or acute bronchitis).

The algorithm encouraged or discouraged antibiotic use according to different PCT cutoff values. They randomized 1359 consecutive adult patients who presented to six tertiary care hospital emergency departments in Switzerland with LRTI diagnosed by clinical and laboratory criteria to receive antibiotic administration according to the algorithm or standard guidelines.

The primary outcome of that study, i.e., incidence of adverse outcomes within 30 days (a composite of death, intensive care unit admission, disease-specific complications, and recurrent infection requiring antibiotics) did not differ significantly between the algorithm and standard guidelines groups (15.4% and 18.9%).

But the good news is that the mean duration of antibiotic exposure and the incidence of antibiotic-associated adverse effects were significantly lower in the algorithm group than in the standard guidelines group (5.7 vs. 8.7 days, respectively, and 19.8% vs. 28.1%, respectively).

Although LRTIs are responsible for more disease and death in the U.S. than any other infection, to date, clinical markers are inaccurate for distinguishing between bacterial and viral infection.

Procalcitonin is released in response to bacterial infection, correlates with severity of LRTI, and is rarely elevated in viral infections. (Note: PCT levels are usually low in viral infections, chronic inflammatory disorders or autoimmune processes whereas the PCT levels in sepsis are generally greater than 1-2 ng/mL and often reach values between 10 and 100 ng/mL, or considerably higher in individual cases, thus enabling the diagnostic differentiation between these various clinical conditions and a severe sepsis)

PCT has the greatest sensitivity (85%) and specificity (91%) for differentiating patients with SIRS from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha (Click here to download a copy of the article).

Besides being highly specific increase in response to severe systemic bacterial infections and sepsis, another major advantage of Procalcitonin (PCT) compared to other parameters is its early rise in response to the infections. Thus, in septic conditions increased PCT levels can be observed 3-6 hours after infectious challenge.

This study demonstrates that a clinical decision rule based on PCT levels can appropriately diminish antibiotic use and help tailor duration of therapy without compromising patient safety.

Reference:
Schuetz P et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The ProHOSP randomized controlled trial. JAMA 2009 Sep 9; 302:1059.

Other references:
1. Christ-Crain M, Stolz D, Bingisser R; et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93. Click here to download in pdf.

2. Nobre V, Harbarth S, Graf JD; et al. Use of procalcitonin to shorten antibiotic treatment duration in septic patients. Am J Respir Crit Care Med. 2008;177(5):498-505. Click here to download in pdf.