Definitions and Impactions
SIRS/Systemic inflammatory response syndrome is a condition that is characterized by signs of systemic inflammation (e.g., fever, leukocytosis). The diagnosis of SIRS requires at least 2 of the following:
1.Temperature >38 C or <36 C
2.Heart rate >90 beats/min
3.Respiratory rate >20 breaths/min, or arterial PCO2 <32 mm Hg
4.WBC count >12,000/mm3 or <4000/mm3, or >10% immature neutrophils (band forms)
Sepsis is a kind of SIRS caused by an infection.
Severe sepsis is a sepsis condition accompanied by dysfunction in one or more vital organs, or an elevated blood lactate level (>4 mM/L).
Septic shock is a severe sepsis accompanied by hypotension that is refractory to volume infusion.
Inflammatory injury involving more than one vital organ is called multiorgan dysfunction syndrome (MODS), and the subsequent failure of more than one organ system is called multiorgan failure (MOF).
The organs most often damaged by systemic inflammation are the lungs, kidneys, cardiovascular system, and central nervous system. The most common manifestation of inflammatory organ injury is the acute respiratory distress syndrome (ARDS), which has been reported in 40% of patients with severe sepsis, and is one of the leading causes of acute respiratory failure in critical ill patients.
The number of organs that are damaged by inflammatory injury has important prognostic implications. There is a direct relationship between the mortality rate and the number of organ failures related to inflammation. This demonstrates the lethal potential of uncontrolled systemic inflammation.
The Physiologic Characteristics of Septic Shock
Severe sepsis and septic shock have been implicated in one of every four deaths worldwide, and the incidence of these conditions is steadily rising. The mortality rate averages about 30-50%, and varies with age and the number of associated organ failures. The mortality rate is not related to the site of infection or the causative organism, including multidrug-resistant organisms. This observation is evidence that inflammation, not infection, is the principal determinant of outcome in severe sepsis and septic shock.
- The principal hemodynamic problem is systemic vasodilatation (involving both arteries and veins), which reduces ventricular preload and ventricular afterload. The vascular changes are attributed to the enhanced production of nitric oxide (a free radical) in vascular endothelial cells.
- Oxidant injury in the vascular endothelium (from neutrophil attachment and degranulation) leads to fluid extravasation and hypovolemia, which adds to the decreased ventricular filling from venodilation.
- Proinflammatory cytokines promote cardiac dysfunction (both systolic and diastolic dysfunction); however, the cardiac output is usually increased as a result of tachycardia and volume resuscitation.
- Despite the increased cardiac output, splanchnic blood flow is typically reduced in septic shock. This can lead to disruption of the intestinal mucosa, thereby creating a risk for translocation of enteric pathogens and endotoxin across the bowel mucosa and into the systemic circulation. This, of course, will only aggravate the inciting condition.
The typical hemodynamic pattern in septic shock includes low cardiac filling pressure (CVP or wedge pressure), a high cardiac output, and a low systemic vascular resistance (SVR). Because of the high cardiac output and peripheral vasodilatation, septic shock is also known as hyperdynamic shock or warm shock. In the advanced stages of septic shock, cardiac dysfunction is more prominent and the cardiac output is reduced, resulting in a hemodynamic pattern that resembles cardiogenic shock (i.e., high CVP, low CO, high SVR). A declining cardiac output in septic shock usually indicates a poor prognosis.
The impaired energy metabolism in septic shock is not the result of inadequate tissue oxygenation, but is caused by a defect in oxygen utilization in mitochondria. This condiditon is known as cytopathic hypoxia, and the culprit is oxidant-induced inhibition of cytochrome oxidase and other proteins in the electron transport chain. A decrease in oxygen utilization would explain the observation that the PO2 in skeletal muscle is increased in patients with severe sepsis.
The proposed decrease in oxygen utilization in sepsis is not consistent with the increase in whole-body O2 consumption that is often observed in sepsis. This discrepancy can be resolved by proposing that the increased O2 consumption in sepsis is not a reflection of aerobic metabolism, but is a manifestation of the increased O2 consumption that occurs during neutrophil activation (i.e., the respiratory burst).
The discovery that tissue oxygenation is (more than) adequate in severe sepsis and septic shock has important implications because it means that efforts to improve tissue oxygenation in these conditions (e.g., with blood transfusions) are not justified.
Serum Lactate Levels
The increase in serum lactate levels in severe sepsis and septic shock is not the result of inadequate tissue oxygenation, but instead appears to be the result of enhanced production of pyruvate and inhibition of pyruvate dehydrogenase, the enzyme that converts pyruvate to acetyl coenzyme A in mitochondria. Endotoxin and other bacterial cell wall components have been implicated in the inhibition of this enzyme. This mechanism of lactate accumulation is consistent with the notion that tissue oxygenation is not impaired in severe sepsis and septic shock.
The management of septic shock is outlined in Table 14-3, and is organized in "bundles", which are sets of instructions that must be followed without deviation to provide a survival benefit. The acute sepsis bundle is considered the most important, and must be completed within 6 hours after the diagnosis of septic shock.
Volume resuscitation is often necessary in septic shock because cardiac filling pressures are reduced from venodilatation and fluid extravasation. The volume resuscitation requires the insertion of a central venous catheter to monitor the central venous pressure (CVP).
1.Infuse 500-1,000 mL of crystalloid fluid or 300-500 mL of colloid fluid over 30 minutes.
2.Repeat as needed until the CVP reaches 8 mm Hg, or 12 mm Hg in ventilator-dependent patients.
If CVP measurements are not available, a volume of at least 20 mL/kg (crystalloid fluid) can be used for the volume resuscitation.
After the initial period of volume resuscitation, the infusion rate of intravenous fluids should be reduced to avoid unnecessary fluid accumulation. A positive fluid balance is associated with increased mortality in septic shock, so attention to avoid fluid accumulation will improve the chances of a favorable outcome.
If hypotension persists after the initial volume resuscitation, infusion of a vasoconstrictor drug (vasopressor) like norepinephrine or dopamine should begin. Vasoconstrictor drugs must be infused through a central venous catheter, and the goal is to achieve a mean arterial pressure (MAP) >=65 mm Hg.
Norepinephrine is favored by many because it is more likely to raise the blood pressure than dopamine, and is less likely to promote arrhythmias. However, neither agent has proven superior to the other for improving the outcome in septic shock.
When hypotension is refractory to norepinephrine and dopamine, vasopressin may be effective in raising the blood pressure (Vasopressin is used as an additional pressor rather than a replacement for norepinephrine or dopamine). Vasopressin is a pure vasoconstrictor that can promote splanchnic and digital ischemia, especially at high dose rates. Although vasopressin may help in raising the blood pressure, the accumulated experience with vasopressin shows no influence on outcomes in septic shock.
Corticosteroids have two actions that are potentially beneficial in septic shock: they have antiinflammatory activity, and they magnify the vasoconstrictor response to catecholamines. Unfortunately, after more than 50 years of investigations, there is no convincing evidence that steroids provide any benefit in the treatment of septic shock. Yet steroids therapy continues to be popular in septic shock. The following comments reflect the current recommendations regarding steroid therapy in spetic shcok.
1.Steroid therapy should be considered in cases of septic shock where the blood pressure is poorly responsive to intravenous fluids and vasopressor therapy. Evidence of adrenal insufficiency (by the rapid ACTH stimulation test) is not required.
2.Intravenous hydrocortisone is preferred to dexamethasone (because of the mineralocorticoid effects of hydrocortisone), and the dose should not exceed 300 mg daily (to limit the risk of infection).
3.Steroid therapy should be continued as long as vasopressor therapy is required.
For the pharmacotherapy of antimicrobial therapy please view the thread of Systematic Approach for Selection of Antimicrobials at http://www.tomhsiung.com/wordpress/2014/03/systematic-approach-for-selection-of-antimicrobials/