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This thesis hypothesizes the use of serum lactate as a metabolic indicator of high risk patients. Sepsis severity depends on levels of prevalence and the response time taken in administering therapy. This article starts by giving the fundamental definitions regarding sepsis, serum lactate,septicemia, septic shock and severe sepsis and their effects on human health. It discusses the history of sepsis, the mortality and morbidity rates, its global economic burden and the counter measures prompted to control mortality and morbidity. It explores the various studies that have been conducted in this field, their findings and their contribution in the current status of pathology. Some of the measures and/or indicators of mortality in septic patients explored include red blood cell transfusion, base deficits (BD), lactate-pyruvate ratios, fluid therapy, Early Goal Directed Therapy (EGDT, anion gap and vasopressor support.
Under normal conditions, 90 percent the body's energy is supplied via processing of carbohydrates and fats by the body cells in the presence of oxygen, water and carbon dioxide are the by products of the process excreted through sweating and breathing respectively. This process is called the aerobic metabolism. Cases when oxygen supply to the cells is low may be as a result of oxygen deficiency into the bloodstream from the lungs, activate anaerobic metabolism. Oxygen deficiencies may be as a result of decreased blood volume (hypovolemia), myocardial depression, increased activity leading to increased metabolism, and perfusion abnormalities. Carbohydrates are combusted in the oxygen deficit to maintain optimal levels of energy in the muscles. Lactic acid is the by product of anaerobic metabolism implying that whenever oxygen levels are low serum lactate start to rise. Liver purifies blood and lactic acid is one of the blood impurities cleared from the blood stream. Lack of balance between the production of lactic acid and its removal leads to a condition referred to as lactic acidosis. Other mechanisms used to strike out the imbalance are lowering the oxygen concentration in the veins by mixed venous saturation signal and increasing in oxygen extraction (Antinone & Kress T., 2009).
Serum lactate level measures the amount of lactic acid in the blood. It is used in indicating tissue hypoxia and tissue hypoperfusion. According to Meragalli et al., (2004), hypoperfusion is as a result of lack of balance between the oxygen required by the tissues to satisfy metabolic needs and the supplied oxygen. Severe cases of hypoperfusion lead to organ failures.
Sepsis is the fighting back of the body against severe infections which may arise as a result of weak defense system or toxic substances, spread by the blood stream. This action is generally referred as sepsis. The toxic substances can either be due to due to fungal infections or bacterial infections in the blood system. Septic patients fulfill at least two of the following signs and symptoms; increased respiratory rates (tachypnea- more than twenty breaths per minute), low body (hypothermia) or high body temperatures (Hyperthermia), from low blood pressure, rapid heart beats (tachycardia-ninety beats per minute at rest) and abnormal white blood cell count. Statistics has revealed an average of 3-5% of patients in the intensive care unit is affected by sepsis leading to 35-50% mortality rates. High levels of serum lactate have been found in septic patients (Vincent et al., 2002). Other conditions that may develop as a result of sepsis include septicemia, septic shock and severe sepsis. Septicemia is the sepsis as a result of bacteria where as severe sepsis is associated with organ dysfunction. Septic shock is caused by elevated lactate concentrations and high oxygen concentrating in the veins.
Globally sepsis affects 2-14% of intensive care unit admissions with mortality rates of about 50%. This figures increase depending on the level definition of the sepsis. The United States records approximately half a million cases of sepsis annually (Centre for Disease Control data) with a decadal average increase rate of 1.39%. Factors accounting for the increase are better health care leading to the discovery of more that would otherwise have not been discovered, increase in proportion of both the young and the elderly, advanced use of immunosuppressant in chronic diseases and invasive devices. It is estimated that the annual cost of the disease is at $ 16.7 billion (Vincent et al., 2002).
A study by Rivers et al., (2001) carried out a study trying to establish the impact of early administration of the Goal-directed therapy. It involved random selection of patients with septic shock or severe sepsis assigning them either the goal therapy or the standard therapy (this acted as control experiment in this case) six hours before admission to the intensive care unit. The scores for APACHE II (Acute Physiology and Chronic Health Evaluation) were significantly low (13.0±) in patients who were subjected to early goal-directed therapy. Those subjected to the standard therapy had high APACHE II scores of 15.9±6.4 an indication of severe organ dysfunction
Recent research studies converge that there seems to be an increasing trend in mortality rates due to elevated serum lactate levels, Serum lactate levels may be key indication in determining high risk patients (Mercier 2007). In the recent past severe conditions such as heart attack (myocardial infarction) and stroke have recorded low mortality rates due to improved medical conditions, early diagnosis and application of time sensitive medication, similar approach if well applied could yield significant results. Although low blood pressure or hypotension is currently used to characterize the transitions of sepsis to septic shock, it has a limitation as it can not detect sepsis at initial sepsis.
PURPOSE OF STUDY
The rationale of this study is to use serum lactate as a metabolic indicator of high risk patients. Researches have indicated that lactate levels greater than 4mmol/L indicate tissue hypoperfusion. Instead of using arterial lactate levels which take long, you can use peripheral venous lactate levels. Early detection of levels of serum lactate during emergency can also be done using point-of -care devices
Weil & Afifi, (1970)conducted one of the earliest empirical study investigating to what levels are the increase in lactate, abbreviated as L (for this study) and pyruvate (P) in arterial blood indicate oxygen deficit and irreversible tissue injury. As a trial Hemorrhagic shock was initiated in the witstar rat using a standardized method and subjected to four hour bleeding. The lactate and pyruvate quantities were obtained by adding blood directly to a cold metaphosphoric (50g/L) acid solution. They found out that the rats oxygen consumption was cut down by almost 40% compared to the control experiment, increases in both pyruvates (P) and lactate (L) by 0.07 to 0.18 mm and 0.80 to 6.06 mm respectively. The pH reduced from 7.39 to 7.08. The log of lactate (L) had correlation levels of 0.5 with the cumulative oxygen debt. From this they also found out that the log of lactate (L) and cumulative oxygen debt had significant correlations with correlation of survival and cumulative oxygen debt. Correlating them partially revealed that not even lactate pyruvate ratio (L/P) or excess lactate (XL) could improve the accuracy of predictability. This study was extended to 142 patients. Using discriminant function analysis it was evidenced that the combination of lactate, excess lactate and the lactate/ pyruvate ratio did help in bringing distinction. There conclusion was only lactate was the important factor in the predictability, pyruvate and the combined ratios are of no importance.
A study by Rivers et al., (2001) tried to establish the impact of early administration of the Goal-directed therapy. It involved random selection of patients with septic shock or severe sepsis assigning them either the goal therapy or the standard therapy (this acted as control experiment in this case) six hours before admission to the intensive care unit. The patients were required to have a systolic blood pressure with a maximum of 90 mm Hg or a blood lactate of more than 4mmol/L. The scores for APACHE II (Acute Physiology and Chronic Health Evaluation) were significantly low (13.0±) in patients who were subjected to early goal-directed therapy. Those subjected to the standard therapy had high APACHE II scores of 15.9±6.4 an indication of severe organ dysfunction
A more detailed study of the above mode, Early Goal Directed Therapy (EGDT) was developed to help in curbing the rates of mortality. It included evaluating the level of the frequency of the sepsis and mortality rate, classifying the vulnerability of the patients basing on pathogenesis, resource mobilization, assessment of outcomes, blood flow abnormalities reversals. This study established the importance of Scvo2 and ScÅ«o2. ScÅ«o2 represents the blood oxygen concentration entering the right hand side of the heart. This helps in determining the tissues body's oxygen demand against supply. This research established that low levels of Scvo2 in initial sepsis conditions can be translated as an indicator of mortality. It recommends 70% of Scvo2 and 65% of ScÅ«o2 for recovery from severe sepsis conditions. (Nguyen et al., 2006)
The EGDT study also discovered that inotropic therapy by the likes of Hayes et al was not successful due to poor patient selection, bad timing and poor dosage of dobutamine therapy. In the EGDT dobutamine was administered increasingly at the rate of 2.5 g/kg/min for
every 15 to 20 min to maintain constant blood pressure and achieve an Scvo2 of greater than 70%. Other approaches applauded by the EGDT is the early use of antibiotics, red blood cells transfusion with 7-9 mg/dL hemoglobin concentrations was critically ill patients (Nguyen et al., 2006)
A study by Mikulaschek A., et al., (1996) trying to verify whether can be predicted by anion gap or base revealed that neither of the two can predict lactate. This study involved 52 patients, 43 survivors and 9 dead, with trauma admitted to the intensive care unit. Anion gaps, Lactate and base excess were recorded at the beginning and after every 8 hours with the maximum at 48 hours. The results indicated high serum lactate in the dead at sixteen hours after admission compared to the survivors with the greatest difference 48 hrs after admission. There was no significant difference in lactate, anion gap and bases between the dead and survivors, neither was there correlation between lactate and base excess nor lactate and anion gap.
Mikkelsen et al., (2009) carried out a study to find out whether organ dysfunction and shock is related to mortality and initial serum lactate. The danger factor was initial venous lactate measured in mmol/L scaled as follows; low for two and less than two, intermediate for anything between 2 and including 3.9, high was from for and above. The variability was introduced via age, sex, race, severity of illness, acute and chronic organ dysfunction and initiation of EGDT. Initial serum lactate was linked with mortality independent of organ dysfunction and shock in patients admitted to the emergency department with severe sepsis. High and intermediate serum lactate levels were not dependent on mortality.
Using 50 adult patients with trauma in the intensive care unit and 25 healthy adults as control experiment, a study conducted by Kadam et al., (2003) found out that base deficits (BD) high levels of serum lactate are indicators of tissue hypoxia. The patients were further divided into three groups depending with the base deficit scales; group I - BD 3 to 5.9, group II - 6 to 14.9, group III-15. This study measured the serum lactate, base deficit and lactate pyruvate at the beginning of the study and after every six hours thereafter. The ratio of Lactate to pyruvate and serum lactate were high in patients admitted with trauma compared to the normal people admitted as control experiment. Notable highs were noted in the base deficit group II with 0.516±0.36 mmolL-1, L/P ratio 7.72±2.49 and group III with 0.66±0.134 mmolL-1, 10.99±2.16 unlike group I 0.362±0.049 mmolL-1, 5.63±1.77. The serum lactate levels were directly proportional base deficit. The serial estimation of serum lactate and decline in values are useful in predicting the mortality of trauma.
This study similar to the above was conducted by Hosein et al., but using 10 children with an average age of 4.9 years. The lactate to pyruvate ratio (LP), lactate and pyruvate was monitored in relation to cardiac index and oxygen delivery to the onset of hyperlactataemia after fontan operation at intervals of thirty minutes for twelve hours. The driver force behind this was the fact that tissue hypoxia in situations of relative oxygen debt, as a result of low cardiac output may lead hyperlactataemia. PiCCO was used in measuring the cardiac index at intervals of four hours. Their results indicated strong correlations between subcutaneous tissue lactate and serum lactate were strongly correlated with 0.87 as the correlation coefficient. The average blood lactate rose to 3.73 mmol l-1 from 2.23 mmol l-1 in the first five hours. The tissue microdialysis results revealed both pyruvate and lactate rose with lactate values rising from 3.8 to 5.3 while LP ratio remained low an indicator of sufficient oxygen supply to the tissues. The oxygen delivery increased from 4556 to 6076 ml min-1 just like the cardiac index from 2.83 (0.63) to 3.77 (1.34) l min-1 m-2.
Both serum levels of interleukin and blood lactate and those of tumor necrosis factor in patients with septic shock have been found to correlate with prognosis. This study was therefore aimed at defining the relative value of these measures. The study finds that irrespective of the modern cardiovascular support and antibiotic therapy, the number of deaths from septic shock is still large. The overall mortality however was found to depend on a number of factors including the severity of shock, the earlier health condition, the extent of organ failure as well as the age of the patient. Poor prognosis of this disorder has been attributed to the development of tissue hypoxia and excessive response from systemic immunology. The study revealed that the main mediators of sepsis in humans are interleukin-6 and (TNFÎ±) tumor neurosis factor. TNFÎ± is found to be crucial in starting many of the alterations linked with septic shock such as altered metabolism and hypotensive. It also revealed that exogenous recombinant administration doesn't induce hemodynamic alterations in dogs but has been linked with the response of metabolism to sepsis which entails synthesis of sharp phase reactants. Data from the study showed that the big variability in (TNFÎ±) tumor neurosis factor and IL-6 levels is what limits the significance of prognosis in patients with septic shock. They then concluded that the predictive value of cytokine levels with time is not greater than the predictive value of blood lactate levels (Marecaux G., et al., 1996.).
There have also been attempts to use vasopressor support in treating septic shock as an alternative when fluid administration fails. Hollenberg, (2007) argues that much as the ultimate activity to be carried out on a shock patient is restoring pressure and perfusion, blood pressure does not always translate to blood flow. It is therefore important to note that despite restoration of arterial pressure normalization of cellular metabolic activities may fail. In his article he points out the need for clinicians to come out with well defined end points to facilitate efficacy of vasoactive agents( examples of vasopressor agents are dopamine, norepinephrine, phenylephrine, epinephrine, vasopressin). In this article he states different catecholamine agents have different effects on pressure and flow. This article recommends the use of arterial cannula to provide accurate arterial pressure rather than the cuff on shock patients. For response t o therapy the study recommends the use of hemodynamic monitoring due to the possibilities of rapid hemodynamic changes and low levels of accuracy by noninvasive evaluation.