الفهرس 
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Abstract
Severe sepsis and septic shock are a leading cause of death in
the world [1] . Sepsis represents a continuum from an inciting
infectious event and the consequent host-pathogen interaction ,
possibly leading to hemodynamic consequences caused by proinflammatory,
anti-inflammatory, and apoptotic mediators. In some
cases sepsis can evolve into severe sepsis, when documented or
suspected infection is associated with multi-organ involvement and
failure, or even into septic shock, when hypotension becomes
unresponsive to fluid therapy and vasopressor are required.
Early recognition of sepsis is not always straight forward and
clinical signs at presentation can be misleading and very
heterogeneous in the population, due to frequent Comorbidities and so
may evolve into septic shock, which is a more severe illness with a
much higher mortality rate.
Despite the international recommendation of an early goaldirected
therapy [4], based on optimization of mean arterial pressure
,central venous pressure, urine output, and central venous oxygen
saturation (ScvO2), mortality rate remains high in septic shock [5-7].
There is a need to test the prognostic value of factors that could be
used for guiding therapy after the initial resuscitation.
We intended in our study to compare & evaluate the effect of
optimizing lactate clearance versus ScvO2 during early hours as target
goals of sepsis resuscitation and also to evaluate this effect as a
prognostic value on ICU length of stay, hospital length of stay, and its
impact on mortality .
We included a prospective observational study of 40 adult
critically ill patients diagnosed to have severe sepsis or septic shock
through their admission to ER department , ICU stay , hospital stay&
28 day mortality at Menoufyia university hospitals then randomly
assigned into 2 groups . Each consisted of 20 patients;
1. group (V), The ScvO2 group :
Resuscitation done to achieve a central venous pressure of 8
mm Hg or higher, the mean arterial pressure goal of 65 mm Hg or
higher, cultures obtained prior to administration of antibiotics, broad
spectrum antibiotics administered this was completed within 3 hours ,
If these targets were not achieved with fluid administration, initiating
and titrating vasopressors (dopamine or norepinephrine) to achieve
this desired blood pressure goal.
Finally, the ScvO2 goal of 70% or higher targeted after
previous targets were met. If the ScvO2 was lower than 70% and the
hematocrit was lower than 30%, packed red blood cells were
transfused to achieve a hematocrit of at least 30%. Dobutamine at a
dose of 5 μg/kg/min if Ht≥30% and ScvO2 ≤70 to reach a target goal
of 70% or higher .
2. group (L) lactate clearance group :
The same previous targets as MAP, CVP, titrating vasopressors
(dopamine or norepinephrine) to achieve this desired blood pressure
goal.
Then lactate clearance goal of 10% or more at the first delayed
measurement and if the hematocrit is less than 30%, packed red blood
cells were transfused to achieve a hematocrit of at least 30%.
dobutamine initiated and titrated in attempts to achieve a lactate
clearance of at least 10%. if LCR remained lower than 10%.
All patients underwent History taking , Hemodynamic
assessment, Thorough Clinical examination . Routine Laboratory
investigations , Microbiological studies. lactate measurement on
admission , lactate clearance in group L &ScvO2In group V at
H0H6, H12, H24, H48 and H72 were analyzed .Survival was
followed-up during 28 days . mortality rates recorded , compared
between both groups then intragroups between survivors and
nonsurvivors .
Our results regarding ScvO2 demonstrated that Target goal of
ScvO2 of 70 % or more was achieved in 90 % of patients in the
central venous saturation group , but with mortality of 45% with
statestically insignificant measurments between survivors and non
survivors (p value> 0.05). throughout the different time interval
during the first 72 hr of resuscitation , with poor prediction of death
at any time.ScvO2 seems to be a useful parameter for initial
resuscitation but is unable to distinguish survivors and nonsurvivors
after this stage. also ScvO2 was high ,(79.3 ±10.6) on admission ,
this means venous hyperoxia The protocols treat venous hyperoxia the
same as normoxia This may lead error while performing
resuscitation which is actually prognostically worse than venous
hypoxia (ScvO2 < 70%). This point highlights the shortcoming of
sepsis resuscitation protocols that focus on the correction of a low
ScvO2 level, signifying impairment in macrovascular oxygen
delivery.. Such a situation does not occur if lactate parameters are
evaluated and clearing lactate levels almost always signifies
improvement in host oxygen utilization signifying the value of lactate
clearance .
Our results regarding Lactate clearance demonstrated that target
goal of Lactate clearance 10 % or more was achieved in 75 % of
patients in the Lactate clearance group , comparing it with Central
Venous Oxygen Saturation as goals of early sepsis resuscitation we
found that targeting lactate clearance of at least 10% as evidence of
adequate tissue oxygen delivery is an effective measure of total body
oxygen metabolism compared to ScvO2 when resuscitating patients
with severe sepsis and septic shock .Also According to this study,
absence of lactate clearance during the first 24 hours is associated
with mortality in septic ICU patients and should lead to therapy
intensification, even in patients who reach standard hemodynamic
target . Fluid resuscitation therapy under the guidance of LCR is
accurate and reliable in patients with severe sepsis and septic shock .
Thepresent research showed discrepancy between lactate and
ScvO2 regarding their correlation with mortality , as we demonstrated
, Target goal of Lactate clearance 10 % or more was achieved in 75 %
of patients in the Lactate clearance group , but with mortality of 30%
so this group had 15% lower in-hospital mortality than those
resuscitated to an ScvO2≥70% . (30% vs 45% respectively) with
statestically significant difference in blood lactate level and lactate
clearance measurements in survivors and non survivors throughout
different time interval during the first 72 hr of resuscitation (p<0.05)
highly significant at 24 hour. (p<0.001). compared with ScvO2 group
which showed no statestically significant difference throughout the
different time measurments (p> 0.05.thus, indicating the value of
lactate clearance as predictive of mortality compared to Scvo2.
Finally, the calculation and interpretation of lactate clearance
appeared useful even after the “golden hours” and enable detection of
patients with a high risk of death.
So, ScvO2 measurement seems to be an interesting tool,
especially in the early phase of shock to guide fluid management and
blood transfusion or inotropic support. Nevertheless, a large
knowledge of its determinants and the physiology of circulation seem
to be essential to ensure a reliable interpretation in clinical practice.
In conclusion, early sepsis resuscitation remains a dynamic
topic of research in this randomized trial, during severe sepsis or
septic shock , a protocol that used lactate clearance compared with
that used ScvO2 as the method of measuring total body oxygen
metabolism found that lactate clearance of at least 10% at a minimum
of 2 hours after resuscitation initiation is a valid way to assess initial
response to resuscitation in severe sepsis. and septic shock . Lactate
normalization during resuscitation is a more powerful indicator of
resuscitative adequacy; however, further research on the optimal
lactate clearance parameters to use during resuscitation and many
other important questions have yet to be answered . Also , Assessment
of lactate clearance in the first 24 hours would be useful for tracking
patients who remained at high risk of death despite achievement of
early goals determined by international recommendations. As
summarized in this report, lactate clearance, as opposed to ScvO2, is
more appropriate goal to choose. Further clinical trials are needed to
conclusively establish lactate clearance as a resuscitation end point
and an outcome measure to be targeted during the most proximal
phases of severe sepsis and septic shock.