Misc. past college questions

Question 1

What are the current Sepsis 3 definitions for sepsis and septic shock (20%)
Discuss the challenges of developing definitions for sepsis and septic shock and the advantages of standardised definitions (80%)

Answer 1

Sepsis 3 definitions:
Sepsis = life threatening organ dysfunction due to a dysregulated host response to infection
Organ dysfunction = increase of 2 + of SOFA score ( every 2 points = 10% mortality
qSOFA = HAT
Hypotenion < 100 systolic
Altered mental status < GCS 15
Tachypnoea RR>22

Septic shock = sepsis plus ( despite adequate fluid resus) lactate 2 or more and hypotension requiring vasopresors.

Advantages of standardised definitions:
*Universal application -allows healthcare providers to reocognise / identify potential sepsis and septic shock early
*Standardised definitions facilitate speaking of a common language in and out of critical care environement
*Standardised definitions also helpful for research, evaluating new and comparing therapies

Challenges of developing definitions:
*Sepsis as a concept is difficult to define
*Despite old SIRS definitions being recognised as not as helpful - world wide mortality has still declined
*There is no gold standard to compare any new definition to
*Still heavily reliant on ‘expert opinion’ for development
*Some components of new definitions e.g. Lactate - not universally available - bias toward resource rich countries.
*Some components of definitions e.g. SOFA qSOFA not well known about outside of critical care

Question 2

Critically evaluate the role of Early Goal Directed Therapy in Septic Patients

Answer 2

*EGDT = *
A protcolosied approach to early ( within 6 hours) targeted management of specific (haemodynamic parameters and goals) with early interventions eg. abx / fluids / vasopressors / inotropes and blood

Rationale:
Aim to improve O2 delivery to tissues
Sepsis associated with risk of shock development - i.e. inadequate O2 delivery
Improved O2 delivery shown to improve outcome

Early Goals =
1) CVP 8-12mmHg
2) MAP >65mmHg
3) u/o >0.5ml/kg/hour
4) Scv02 > 70%
5) Hematocrit > 0.3

Advantages =
* Surviving sepsis guidelines continue to endorse EGDT
* Rivers trial demonstrated improved survival with ScVO2 monitoring vs standard care
* MAP goals are evidence based
* MAP, CVP and SvO2 generally able to be assessed easily in critical care
* ScVO2 is predictive of outcomes

Disadvantages =
* Excessive O2 delivery is not benign
* Protocols for implementing EGDT usually result in more fluid administration and more vasoactive use
* R/o adverse effects of blood transfusion
* PAC / not routinely placed

Evidence

RIVERS TRIAL ( NEJM 2001)
P = American single centre 263 patients with sepsis or septic shock
I= Protocol including EGDT for 6 hours - CVP 8-12, Hct >0.3, Scv02 >70, MAP>65
C=Usual care
0=Significant benefit of EGDT in survival.

Critique: - single centre study, conflict of interests e.g. lead author and manufacture of ScVO2 measuring CVC.

ProCESS TRIAL (NEJM 2014) US
P = RCT of adults (n= 1351) with suspected sepsis arriving to ED in the US
I = Protocolised EGDT based on Rivers study for 6 hours
C = usual care
O = No difference in mortality

ARISE TRIAL (NEJM 2014) (AUSTRALIA/NZ)
P = Multi centre RCT of adults ( n=1600) with suspected sepsis
I = EGDT based on Rivers study for 6 hours
C = usual care with NO ScVO2 measurement
0 = No difference in mortality

ProMIse TRIAL ( NEJM 2015) UK
P= Multi centre UK RCT of adults ( n= 1260) with suspected sepsis
I= EGDT for 6 hours based on Rivers study with CVC for ScvO2 and Aline inserted
C= Usual care with Aline / CVC prn
O= no difference in mortality

-3 landmark trials show no difference in mortality for EGDT vs usual care.
- Usual care often included use of CVC and MAP targets anyway but didn’t involve use of continuous monitoring of ScV02 or CVP to guide management.
-Multicentre, international evidence presented in robust randomised trials

Own approach to Sepsis:

• Recognise suspected sepsis early
• Simultaneous assessment, monitoring and management
• Early blood cultures and antibiotics
• Optimise filling state up to 30ml/kg crystalloid
• Optimise haemodynamics and O2 delivery to tissues - >
  ○ Early consideration of Aline MAP > 65 in most patient groups
  ○ Don’t delay vasopressors for CVC but consider early if req noradrenaline
  ○ Optimise oxygenation
• No robuse evidence for routine static CVP measurements
• No robust evidence to support routine continuous ScVo2 monitoring