Cardiovascular system
Early goal-directed therapy aims to prevent sudden deterioration of the cardiovascular system, improve oxygen delivery and prevent tissue hypoxia. After adequate volume resuscitation, this is achieved with the help of vasopressor agents such as noradrenaline or adrenaline; however, this is associated with increased tissue oxygen demand, and decreased renal and mesenteric blood flow.
Vasopressin, a potent vasoconstrictor, has an established role in systemic arterial pressure maintenance. In septic shock, a relative vasopressin deficiency along with enhanced sensitiv- ity exists. Vasopressin acts on the VIa receptors in the vascular smooth muscle and produces organ-specific vascular effects, including vasodilation of the cerebral, coronary and pulmonary vessels, and vasoconstriction of the skeletal and skin blood vessels. Vasopressin also decreases the noradrenaline requirement significantly.
Respiratory system
Respiratory failure in septic shock frequently leads to acute respiratory distress syndrome (ARDS), which requires mechanical ventilation. Despite advances in mechanical ventilation strategies, the mortality is around 36 per cent (which has decreased from 50 per cent over the past decade). Acute respiratory distress syndrome is diagnosed by acute onset of severe respira- tory distress with bilateral pulmonary infiltrates consistent with pulmonary oedema. This bilat- eral non-cardiogenic pulmonary oedema leads to varying degrees of refractory hypoxemia. A PaO2/FiO2ratio of 200 or less is defined as ARDS. The aetiology is usually pulmonary or extra- pulmonary in origin. The causes are shown in Table 9.3. Sepsis-associated ARDS carries the highest mortality. The pathogenesis of ARDS involves endothelial dysfunction and loss of epithelial integrity, resulting in alveolar oedema and damage to type II pneumocytes, which Table 9.3 Causes of acute respiratory distress syndrome
Pulmonary Extrapulmonary
Aspiration Sepsis
Pneumonia Shock
Near-drowning Trauma
Smoke inhalation Pancreatitis
Burns Fat embolism
Pulmonary contusion Multiple blood transfusion Cardiopulmonary bypass
Summary causes surfactant deficiency. Atelectasis results in increased shunt, leading to refractory hypox- aemia. Management of ARDS includes mechanical ventilation, fluid management and sup- portive treatment of the aetiology.
Mechanical ventilation
Patients with ARDS require intermittent positive-pressure ventilation (IPPV) with positive end expiratory pressure (PEEP). The ARDS Network trial demonstrated a 22 per cent decrease in mortality with 6 mL/kg compared with 12 mL/kg tidal volume ventilation and with a PEEP of 8–12 cmH2O. With low tidal volume ventilation, the respiratory rate may go up to 35 breaths/min in order to clear the carbon dioxide. This can contribute to high levels of intrinsic PEEP, minimising the alveolar recruitment/derecruitment process.
Prone-position ventilation
In the supine position, atelectasis in the dependent region of lungs in ARDS creates large intrapulmonary shunt and hypoxaemia. Prone-position ventilation (PPV) is thought to recruit and ventilate the atelectatic dorsal lung units, thus improving ventilation perfusion and gas exchange.
Newer ventilatory strategies
High-frequency oscillatory ventilation (HFOV) oscillates the lung around a constant mean airway pressure, which allows maintenance of alveolar recruitment while providing low end expiratory and peak pressures.
Novel strategies
Granulocyte–macrophage colony-stimulating factor (GS-CSF) deficiency leads to impaired homeostasis of pulmonary surfactant and the development of an alveolar proteinosis-like dis- ease. GM-CSF restores impaired function of granulocytes and macrophages and haematopoiesis.
Endocrine system
Functional adrenal insufficiency and tight glycaemic control are two important aspects in the management of septic patients. Patients with severe sepsis may develop relative adrenal insuf- ficiency or SIRS-induced glucocorticoid receptor resistance. Studies suggest that, in severe septic patients, hydrocortisone 50 mg every 6 h is beneficial.
Hyperglycaemia and insulin resistance are common in critically ill patients, increasing the risk of complications such as severe infection, critical illness polyneuropathy and multiorgan failure. Van den Berghe et al. (2001) demonstrated that the maintenance of blood glucose between 4.4 mmol/L and 6.1 mmol/L reduced the morbidity and mortality in critically ill patients.
Renal replacement therapy
Acute renal failure is a complication of septic shock that can precipitate life-threatening com- plications such as hyperkalaemia, acidosis and fluid overload. Haemofiltration is the main form of continuous renal replacement therapy (CRRT) used to support renal function in acute renal failure. Critically ill patients do not tolerate the higher flow rates required in haemodialysis and develop hypotension. Septic patients tolerate haemofiltration better with hypotension. The concept of direct removal of pro- and anti-inflammatory mediators from the circulation may interrupt the inflammatory cascade and hence attenuate the septic shock.
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SUMMARY
The treatment of sepsis has changed significantly over the past few years; however, adopting these newer practices can be a real challenge to physicians. In the UK, all intensive care units 123
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME AND SEPSIS
are adopting these practices in the form of ‘sepsis care bundle’ and ‘ventilatory care bundle’. The ‘bundle’ is defined as a group of interventions related to a disease process that, when implemented together, results in a better outcome than when implemented individually. Before initiating a new high-cost therapy, basic measures such as effective resuscitation can make a significant difference in the outcome of the patient.
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QUESTIONS
1What is sepsis?
2What is septic shock?
3What is MODS?
4What is the role of early-goal-directed therapy in septic shock?
5What is ARDS?
6What are the causes of ARDS?
7What is the pathogenesis of ARDS?
8What do you understand by the term ‘PEEP’?
9What is the treatment for ARDS?
10What is activated protein C?
11What is the mechanism of action of activated protein C?
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REFERENCES
Bone RC, Balk RA, Cerra FB, et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: the ACCP/SCCM Consensus Conference Committee – American Col- lege of Chest Physicians/Society of Critical Care Medicine. Chest 101: 1644–55.
Marshall JC (2004). Sepsis: current status, future prospects. Curr Opin Crit Care 10: 250–64.
Rivers E, Nguyen B, Havstad S, et al. (2001). Early goal directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345: 1368–77.
Van den Berghe G, Wouters P, Weekers F, et al. (2001). Intensive insulin therapy in critically ill patients. N Engl J Med 345: 1359–67.
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FURTHER READING
Finney SJ, Evans TW (2001). Mechanical ventilation in acute respiratory distress syndrome. Curr Opin Anaesthesiol 14: 165–71.
Intensive Care National Audit and Research Centre. www.icnarc.org.
Kandasamy R (2006). Current concepts in the management of MODS. Ind J Trauma Crit Care 7: 478–86. Marshall JC (2001). Inflammation, coagulopathy and the pathogenesis of multiple organ dysfunction syn-
drome. Crit Care Med 29: S99–106.
Richard DG (2003). Specialised nutrition support in critically ill patients. Curr Opin Crit Care 9: 249–59.