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

DO2 – VO2 - SvO2

VO2-VCO2 production during shivering

VO2-VCO2 production during agitation

VO2-DO2 dependence

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

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)

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 ?

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.

The beneficial effect of supranormalization of oxygen delivery with dopexamine hydrochloride on perioperative mortality Boyd et al. JAMA 1993;270:2699-2707 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.

Elevation of systemic oxygen delivery in the treatment of critically ill patients Hayes et al. N Engl J Med 1994;330:1717-1722 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

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

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

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

Treatment of Sepsis Hemodynamic Optimization Appropriate ATB treatment

N Engl J Med 2001;345:1368-1377

Chest 2006;

Crit Care Med 2002;30:1686-92

Crit. Care Med 2002;30:1686-92 21 randomized controlled trials Mortality reduction with hemodynamic optimization when treated early before MSOF when group mortality is >20%

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