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Thursday, September 25, 2014

Pathophysiology of sepsis

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


Thursday, March 27, 2014

Emergency Medicine Digest

Selected publications of interest

1. Does a higher MAP target in septic shock confer lower mortality target?
No. A target mean arterial pressure of 80 to 85 mm Hg conferred no mortality benefit over the standard 65 to 70 mm Hg target.

Reference: 
Asfar P et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014 Mar 18; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1312173)

The surviving sepsis campaign 2012 recommends a maintenance of mean arterial pressure (MAP) target of at least 65 mm Hg as part of a sepsis bundle. However, the guideline does not mention whether a higher MAP target might improve mortality and decrease end-organ dysfunction. Neither does the guideline specify an optimal range of MAP.  The guideline simply says "at least" 65 mm Hg.

In a 29-center French study, a group of researchers compared the outcomes in 776 patients with septic shock who were randomized to MAP targets of either 65 to 70 mm Hg or 80 to 85 mm Hg.

They found that there was no significant differences between the lower-target versus the higher-target groups in 28-day mortality (34% and 37%), 90-day mortality (42% and 44%) and even the median intensive care unit length of stay (8 days in both groups).

However, consistent with other previous studies, the higher-target group had a lower incidence of doubling of the blood creatinine level and hence were less likely to require dialysis.

Previously, Dunser et al (2009) showed in a large, retrospective study, that a MAP of more than 75 mm Hg may be required to maintain kidney function. (Ref: Dunser MW, Takala J, Ulmer H, et al. Arterial blood pressure during early sepsis and outcome. Intensive Care Med 2009;35:1225-1233). This notion was later confirmed in another small, prospective, observational study. (Ref: Badin J, Boulain T, Ehrmann S, et al. Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study. Crit Care 2011;15:R135-R135).

Why?  Why did the higher-target group were less likely to require dialysis? The postulated basic physiological mechanism is that chronic arterial hypertension causes a rightward shift in cerebral pressure-flow autoregulation, resulting in a higher targeted mean arterial pressure to maintain organ perfusion (Ref: Strandgaard S, Olesen J, Skinhoj E, Lassen NA. Autoregulation of brain circulation in severe arterial hypertension. Br Med J 1973;1:507-510).

Unfortunately, although the higher-target group were less likely to require dialysis, this benefit seemed to be offset by a significant increased risk of developing atrial fibrillation.

Why? First of all, septic shock per se is a major risk factor for atrial fibrillation (Ref: Walkey AJ, Wiener RS, Ghobrial JM, Curtis LH, Benjamin EJ. Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA 2011;306:2248-2254).

But the high-target group received significantly higher doses and longer duration of vasopressor catecholamines infusion, and this was postulated by the researchers to be related to the higher incidence of atrial fibrillation. Nonetheless, this postulation remains to be verified in future trials.

2. Fixed D-dimer cutoff of 500 µg/L, versus age-adjusted D-dimer to rule out pulmonary embolism

Measurement of plasma d-dimer allows pulmonary embolus (PE) to be ruled out when clinical suspicion is low or moderate, but interpretation is complicated by the fact that d-dimer levels rise normally with age. In a multicenter European study, investigators prospectively evaluated the accuracy of an age-adjusted d-dimer cutoff in 2898 patients with low or moderate clinical probability for PE. - See more at: http://www.jwatch.org/na34001/2014/03/18/age-specific-cutoffs-d-dimer-rule-out-pulmonary-embolus#sthash.Gj3B1o3b.dpuf
Reference: 
Righini M, Van Es J, Den Exter PL, et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study. JAMA. 2014;311(11):1117-1124. doi:10.1001/jama.2014.2135.
Measurement of plasma d-dimer allows pulmonary embolus (PE) to be ruled out when clinical suspicion is low or moderate, but interpretation is complicated by the fact that d-dimer levels rise normally with age. In a multicenter European study, investigators prospectively evaluated the accuracy of an age-adjusted d-dimer cutoff in 2898 patients with low or moderate clinical probability for PE. - See more at: http://www.jwatch.org/na34001/2014/03/18/age-specific-cutoffs-d-dimer-rule-out-pulmonary-embolus#sthash.Gj3B1o3b.dpuf

Measurement of plasma d-dimer can be used to rule out pulmonary embolus (PE) when the pre-test probability using Well's score or revised Geneva score is low but PERC score cannot rule out PE clinically (see a blog post here and here).

Unfortunately, because several studies in the past have shown that D-dimer levels increase normally with age, using a fixed cut-off value of D-dimer to rule out PE is not very useful in the elderly.
For example,  in a previous study, D-dimer test was able to rule out PE in 60% of patients younger than 40 years, but in only 5% of patients older than 80 years. This results in a lot of unnecessary costly investigations being subjected to these older and often fragile patients.

(Ref: Righini  M, Nendaz  M, Le Gal  G, Bounameaux  H, Perrier  A.  Influence of age on the cost-effectiveness of diagnostic strategies for suspected pulmonary embolism. J Thromb Haemost. 2007;5(9):1869-1877.)

In this current multicenter European study (involving 19 centers in Belgium, France, the Netherlands, and Switzerland), investigators prospectively evaluated the accuracy of an age-adjusted d-dimer cutoff (defined as age × 10 in patients 50 years or older) in 2898 patients with low or moderate clinical probability for PE as compared to a fixed the cutoff at 500 µg/mL.

It was shown that using the age-adjusted cutoff resulted in a 12% absolute increase and a 41% relative increase in the proportion of negative d-dimer results without the loss of sensitivity of detecting PE. In those patients with in-between values (between 500 µg/mL and their cut-off value), only one (0.3%) was found to have PE during follow-up.

Hence, from this study, it is suggested that:
  • for patients younger than 50 years old, use the fixed cut-off point for D-dimer at 500 µg/mL.
  • for patients 50 years and older, a D-dimer result was considered negative if it was less than (age in years ×10) µg/mL.
or patients aged 50 and older, a d-dimer result was considered negative if it was less than age ×10 - See more at: http://www.jwatch.org/na34001/2014/03/18/age-specific-cutoffs-d-dimer-rule-out-pulmonary-embolus#sthash.Gj3B1o3b.dpuf
Bear in mind, the usage of CTPA especially in elderly patients is not without risks. Elderly patients are more likely to present with renal impairment and to develop contrast-induced nephropathy. The use of the ventilation-perfusion lung scan is also limited by the higher number of inconclusive results obtained in this age group.

Sunday, February 09, 2014

Funnel or tapered shaped pediatric airway - where does this concept come from?

Pediatric airway, especially for those 2 years of age, has often been described as a funnel-shaped with its narrowest part at the level of the cricoid cartilage (in contrast with the cylindrical adult larynx).

But where does this concept originate from?

Ríos Medina et al (2012) in a review article (click here to download in pdf) stated that it was way back in 1951 when Eckenhoff wrote about the anatomical considerations of the pediatric larynx and their implications for anesthesia.

However, Eckenhoff's article was in turn based on descriptions made half a century before by Bayeux, who reported the findings from anatomic dissections in 15 bodies of children between 4 months and 14 years of age, together with their corresponding plaster models. In that article, Eckenhoff describes the cricoid cartilage as a rigid structure that cannot be distended in order to pass the ETT, and describes how its parts come together to form a ring around the larynx. Eckenhoff actually clearly states the danger of extrapolating such cadaver findings to live human beings. Unfortunately a number of anesthesiology textbooks picked up on these anatomical descriptions of the pediatric airway since then.

In 2003, Litman et al., in a study using MRI on 99 children under 14 years of age showed that the narrowest portion was identified at the cross-sectional diameter of the vocal cords.

Dalal et al. (2009), in another study using video bronchoscopy on 128 children under 13 years of age seems to confirm Litman's findings. Although the approaches are different, the glottis is identified as the narrowest portion and the larynx as being more cylindrical than rather than traditionally taughted to be tapered. Nonetheless, Litman observes that, although his results show that the narrowest portion of the pediatric airway is at the glottis entrance, functionally the cricoid cartilage is a rigid structure that cannot be distended, and it is still the site of the greatest risk for injury.

Although this new concept is probably still evolving,  the clinical implication is that cuffed ET tubes can be used safely just as with uncuffed tubes.

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