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Monday, January 25, 2016

Sensitivity, specificity and likelihood ratios

A short tutorial on sensitivity, specificty and likelihood ratios. A few good tutorials in YouTube are linked below as well.



Sensitivity, specificity and likelihood ratios from Chew Keng Sheng


A good series of 6 short videos on sensitivity, specificity, ROC curve and the concept of the trade-off between sensitivity and specificity:








A short tutorial on likelihood ratios:

Sunday, January 17, 2016

Damage Control Resuscitation

Damage control resuscitation (DCR)
Historically, first described by Rotondo et al in 1993. In that study, although no significant differences were identified between the 22 patients with definitive laparotomy (DL) vs 24 damage control surgery (DC) (with actual survival rates were similar, ~ 55% DC vs. 58% DL), in a subset of 22 patients with major vascular injury and two or more visceral injuries (maximum injury subset), survival was markedly improved in patients treated with damage control (77% vs 11%) (Fisher's exact test, p < 0.02).

Three main phases - damage control surgery aimed to arrest bleeding to limit risk of contamination, Operative time should be limited to 90 min to minimise risk of hypothermia, coagulopathy, and acidemia (Riha et al, 2013); transfer to ICU for resuscitation to normalize tissue oxygen delivery, and resolve acidosis and coagulopathy; and then back to OR again for definitive repair of injuries temporized during damage control surgery.

Four mechanisms of trauma-associated coagulopathy (besides dilutional effect of IV fluids) (Pohlman et al, 2015):
1) a qualitative platelet defect (particularly after traumatic brain injury [TBI])
2) diffuse endothelial cell injury
3) depletion of coagulation factors and platelets through hemorrhage and deposition into injuries,
4) consumption of platelets and coagulation factors secondary to disseminated intravascular coagulation (DIC) or hyperfibrinolysis

Why acidemia is bad? (Pohlman et al, 2015):
Acidemia diminishes coagulation factor enzymatic activity, depletes fibrinogen and reduces the number of circulating platelets.

Acidemia also
(1) decreases cardiac contractility, causes dysrhythmias, which, in effect, may cause cardiogenic shock on hypovolemic shock in the exsanguinating patient.
(2) desensitizes peripheral vasculature adrenergic receptors to endogenous catecholamines disabling compensatory mechanisms in response to hemorrhagic shock
(3) stimulates inflammation, and suppresses immunity

Why hypothermia is bad?
(Pohlman et al, 2015): The enzymatic specificity constants of coagulation factors in hemostatic pathways and platelet activity are negatively affected to a significant degree by hypothermia. Coagulation factor activity is reduced approximately 10%–15% for each 1 °C drop in temperature

Although damage control surgery and resuscitation was initially described following abdominal injury, the basic principle has been extended to all aspects of trauma care
 
Resuscitation
Massive Transfusion (MT): ≥10 units of packed red blood cells within a 24-hour period

The physiology supporting the 1:1:1 (FFP:platelets:PCs) approach is based on the basis of dilutional coagulopathy with conventional transfusion especially so associated with crystalloid (3:1, 3L of crystalloid with 1L of blood).

Neal et al (2012) - Crystalloid resuscitation in a ratio greater than 1.5:1 per unit of PRBCs transfused was independently associated with a higher risk of MOF, ARDS, and ACS.

Holcomb et al (2015) - RCT (n = 680 with major traumatic bleeding) FFP: platelets: PC of 1:1:1 vs 1:1:2.

No significant differences in terms of mortality at 24 hours (12% in 1:1:1 vs 17% in 1:1:2) or at 30 days (22% vs 26% respectively) but patients given 1:1:1 were significantly more likely to have adequate hemostasis (86% vs 78%) and had fewer exsanguination deaths at 24 hours (9% vs 15%).

Other retrospective studies:

Bergman et al (2007) - combat-related trauma, 1:1.4 plasma to RBC ratio is independently associated with improved survival to hospital discharge, primarily by decreasing death from hemorrhage.

Complications of massive transfusion of PCs:
1) Dilution thrombocytopenia
2) Lower fibrinogen levels (give cryoprecipitate)
3) electrolyte abnormalities
4) TRALI/MOF

Platelets:
Every 50 × 109/L increase in admission platelet count decreases odds of death at 6 h decrease by 17% (p=0.03, 95% CI 0.70–0.99), whereas any platelet transfusion within the first 24 h is associated with a lower mortality in injured patients compared to patients who do not receive platelets (p<0 .001="" 95="" br="" ci="">
Tranexamic acid (TXA)
In a Cochrane review, Henry et al (2011) showed that TXA decreases the need for blood transfusion by one-third in patients undergoing high-risk elective surgery

Permissive hypotension:
Landmark study: Bickell et al (1994) NEJM - hypotensive patients who received no IV fluid administration prior to OR and were allowed a lower blood pressure in the pre-hospital and emergency room phases had a higher survival than those who were treated with more fluids targeting a “normal” systolic blood pressure (70% vs 62%, p = 0.04). Extrapolation to blunt trauma (especially with TBI?)

Rationale of permissive hypotension
(1) decreasing the incidence and severity of dilutional coagulopathy and
(2) avoiding the hypothetical “pop the clot” effect, which occurs when the fresh and unstable clot sealing a vascular laceration is dislodged when the intravascular pressure increases.
(3) decreases inflammatory cascade, which is exacerbated in response to IV fluids administration

In an animal study, permissive hypotension >90 - 120 min is associated with worse end-organ damage (Li et al, 2011)
 
Definitive surgery
Definitive repair of injuries temporized during damage control surgery usually starts 24 to 48 hours following initial injury.

References:
  1. Riha GM, Schreiber MA. Update and new developments in the management of the exsanguinating patient. J Intensive Care Med 2013;28(1):46-57. 
  2. Rotondo MF, Schwab CW, McGonigal MD, Phillips GR, Fruchterman TM, Kauder DR, et al. 'Damage control': an approach for improved survival in exsanguinating penetrating abdominal injury. J Trauma. 1993;35(3):375-82
  3. Neal MD, Hoffman MK, Cuschieri J, Minei JP, Maier RV, Harbrecht BG, et al. Crystalloid to packed red blood cell transfusion ratio in the massively transfused patient: when a little goes a long way. J Trauma Acute Care Surg 2012;72(4):892-8.
  4. Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007;63(4):805-13.
  5. Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA 2015;313(5):471-82. Epub 2015/02/04.
  6. Pohlman TH, Walsh M, Aversa J, Hutchison EM, Olsen KP, Lawrence Reed R. Damage control resuscitation. Blood Rev 2015;29(4):251-62.
  7. Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. The Cochrane Database Syst Rev 2011(3):CD001886. doi: 10.1002/14651858.CD001886.pub4.
  8. Li T, Zhu Y, Hu Y, Li L, Diao Y, Tang J, et al. Ideal permissive hypotension to resuscitate uncontrolled hemorrhagic shock and the tolerance time in rats. Anesthesiology. 2011;114(1):111-9.

Sunday, November 22, 2015

BLS and ACLS Updates 2015 - The Malaysian Perspective

A talk that I presented during the Kelantan Resuscitation Updates 2015 (22 Nov 2015) based on the new AHA/ILCOR guidelines. However, I have put in some emphasis on certain aspects which are relevant in the Malaysian setting (for both major referral hospitals as well as smaller, lesser-equipped hospitals/clinics). Basically however, there are no major changes in this year 2015 updates. If you have already been doing well with the Guidelines 2010, you don't really need to waste money for an updated ACLS course. As Justin Morgenstern said it so well

"If I had to take away just 2 learning points, they would be:
  1. These guidelines are very similar to the 2010 guidelines. There are no changes important enough to warrant paying for another ACLS course. If you know the 2010 guidelines, just keep providing good patient care.
  2. As always, the science is weak. Only 1% of recommendations were “level A”, meaning high quality evidence from more than one RCT. The most common phrase I encountered reading through these guidelines was “may be reasonable”. This phrase is essentially meaningless and can easily be translated into “may not be reasonable”. Tread with care."  (Emphases mine, read more in his blog)


ACLS 2015 Updates - The Malaysian Perspective from Chew Keng Sheng


To download this slide in pdf, go to http://www.slideshare.net/cksheng74/acls-2015 and click 'download'.

Anyway, a number of great resources worth mentioning (much better than I can ever produce):

1) Emergency Medicine Cases Podcast has released a 2-part series on ACLS 2015 Guidelines (episodes no 71 and 72 - click here and here to access)

2) Boring EM Blog has released a series of infographics on the Top Five series - top five BLS changes, top five ACLS changes, etc. Beautifully, beautifully done. Great for visual learners. Trust me, it is not "boring"! Click here to download for FREE.

3) This is THE website, THE front page that you should go to for CONTINUOUS updates on BLS, ACLS, PALS, etc. As the American Heart Association has mentioned, there will no longer be a 5-yearly update.  But it is going to be a continuous web-based updates (e.g. the ROC-ALPS trial, of which, the results will probably be published early 2016 and it may shed some light as to whether amiodarone or lignocaine for shockable rhythms may actually improve survival to discharge). Click here and come back here often.

4)  As mentioned above, Justin Morgenstern's take on the first 10 minutes is worth reading. Click here.

5) R.E.B.E.L Em podcast: Our Top Five AHA 2015 Guideline Updates. Click here to download and listen.

6) And finally, of course, download the entire full text of the AHA Guidelines here in Circulation.


It is interesting to note that the highlights of AHA 2015 Guidelines is now also available in Bahasa Malaysia. Click on the image to go to the website to download:

https://eccguidelines.heart.org/index.php/circulation/cpr-ecc-guidelines-2/ 
 

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