1. The golden hour(s) for severe sepsis and septic shock treatment
D. Matamis M.D, Papageorgiou Hospital
Thessaloniki - Greece

2. DO2 – VO2 - SvO2

3. VO2-VCO2 production during shivering

4. VO2-VCO2 production during agitation

5. VO2-DO2 dependence

6. Regional SvO2 ScvO2 jugular SvO2 hepatic SvO2 renal SvO2
coronary sinus SvO2
mesenteric SvO2

7. Tissue Hypoxia O2 reserves DO2/VO2 imbalance Decrease in O2 delivery
Increase in O2 Consumption
O2 reserves
25% of the Ο2 delivered in the
periphery is used
Is it reasonable?
- CaO2 =20 ml/dl
- (a-v)DO2 = 5 ml/dl
- SvO2 75%,
Marathon Runners
Deep Divers (mammals, Birds)

8. Tissue Hypoxia -The Concept of Supra-normal Values
ICU patients
Trauma
Severe Sepsis
Extensive Surgery
If we increase DO2
Mortality
Goals of the hemodynamic optimization
DO2 ?
SvO2 ?, ScvO2 ?
C.I ?

9. The first randomized controlled trial Shoemaker et al
The first randomized controlled trial Shoemaker et al. Chest 1988;94:1176
General surgery high risk patients.
trauma, vascular, acute abdominal catastrophe, extensive ablative surgery
Three groups 1. CVP control group
2. PAC control group
3. PAC protocol group.
Goals of therapy C.I > 4,5 lit/min/m2, DO2>600ml/min/m2,
Reduction in mechanical ventilation (9,4 vs 2.3) and ICU days (15,8 vs 10,2)
146 patients, 55 non randomized, 45 not ill enough, non consecutive enrolled,
severity illness score not employed for baseline comparability, Co-interventions,
hemodynamic and oxygen transport values for each group not reported.

10. The beneficial effect of supranormalization of oxygen delivery with dopexamine hydrochloride on perioperative mortality Boyd et al. JAMA 1993;270:
Dopexamine as the pharmacologic agent to increase DO2
The intervention was initiated preoperative
Patients comparable at baseline
Pre and post op DO2 values were higher in the treatment group
28 days mortality was lower in the treatment group
6% vs 22% p< 0,015
But
The median duration of ICU stay were 40 and 46 hours
In other studies ICU stay ranged from 5 to 24 days
The population in the study of Boyd at al was less critically ill.

11. Elevation of systemic oxygen delivery in the treatment of critically ill patients Hayes et al. N Engl J Med 1994;330:
100 patients
Dobutamine as the pharmacologic agent to increase DO2
Randomization after standard fluid resuscitation
Mortality was higher in the treatment group 48% vs 30%
But
Delay to start the protocol
More seriously ill patients, higher APACHE score in the protocol group
Patients in the protocol group received more aggressive treatment
50 mcg/kg/min Dobutamine and more than 68% Norepinephrine
70% of the patients did not reach the supranormal value

13. Control group MAP > 60 mmHg
Large (762 patients) multi-center randomized trial
Three groups
Control group
Supranormal C.I group
Normal SvO2 group (>70%)
Standard clinical care in all three groups
MAP > 60 mmHg
CVP=8-12
PAOP≤18mmHg
Urine output≥0.5ml/kg
pH ≥ 7,3-7,5
- 55% of the CI group failed to achieve a supranormal value

15. The negative results of these study may be due to failure to achieve treatment goals rather than failure of treatment to influence outcome

16. 7 randomized trials 1016 patients included
Maximizing Oxygen delivery in critically ill patients: A methodologic appraisal of the evidence. Heyland et al. Crit Care Med 1996;24:517-24
7 randomized trials 1016 patients included
Major problem:
crossover of the patients
Time of intervention
Pre or postoperative in the ICU
Timing of inotropic support

17. Treatment of Sepsis
Hemodynamic Optimization
Appropriate ATB treatment

18. N Engl J Med 2001;345:

23. Chest 2006;

28. Crit Care Med 2002;30:

29. Crit. Care Med 2002;30:
21 randomized controlled trials
Mortality reduction with
hemodynamic optimization
when treated early before MSOF
when group mortality is >20%

35. Conclusion Sepsis related mortality and ICU-hospital LOS depends of:
Early detection or screening for high-risk patients
Early detection and treatment of tissue hypoxia
Early administration of appropriate antibiotic treatment
Providing education of all involved personnel