- Email: [email protected]
Sepsis, SIRS and MODS
ORGAN FAILURE
(Pauchet’s manoeuvre) is indicated. Formal total gastrectomy may be unnecessary. High lesser curve ulcers can be treated by direct ulcer excision (not a minor procedure). Surgical therapy for any patient with refractory variceal bleeding represents a significant risk. Schaefer proposes the following good practice guidelines for assessing surgical candidacy. • All patients should have received a diagnostic and at least one therapeutic attempt at haemostasis. • Surgical candidates should include those with failed haemostasis after vigorous resuscitation or those with clinically significant re-bleeding after 12–24 hours of initial haemostasis. • Prohibitive surgical risk: Childs class C. In advanced liver disease, transplantation is the management of choice, but donation yield remains the rate-limiting factor. Transplantation is the optimal portal decompressive shunt and has the advantage of restoring synthetic liver function. The recent 1- and 5-year survival rates are 80% and 60% respectively.
Sepsis, SIRS and MODS Nicoletta Zimbler Anne Campbell
Sepsis, systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) represent progressive stages of the same illness, in which a systemic response to an infection may lead to a generalized inflammatory reaction in organs remote from the initial insult and eventually to end-organ failure. Sepsis is the most common cause of death in the intensive care unit (ICU) and the mortality rate is > 50% in most centres in the UK.
Definitions of sepsis In the past, the terms bacteraemia, septicaemia, sepsis, sepsis syndrome and septic shock were all used to define sepsis, which led to an imprecise understanding of sepsis and its related disorders, and to confusion in the interpretation of clinical trials. In 1991, a new set of definitions were introduced by the Consensus Conference of the American College of Chest Physicians and the Society of Critical Care Medicine (USA). They included bacteraemia, sepsis, septic shock, SIRS and MODS in their definitions (Figure 1). SIRS describes the widespread inflammation that occurs following a wide variety of insults (e.g. infection, pancreatitis, trauma, burns), and hence introduces a concept that endogenous mediators of inflammation play an important role in sepsis. The terms septicaemia, sepsis syndrome, and refractory shock were eliminated by the conference because they are nonspecific. Ten years later, the International Sepsis Definitions Conference tried to change the definition of sepsis. The molecular pathogenesis of sepsis is better understood, but very few studies have produced useful conclusions. One of the major problems in research is the heterogeneity of patients and the problems of trying to make groups of patients comparable. A new staging system for sepsis may be introduced by the International Sepsis Definitions Conference that will include information on predisposing factors, infection, host response and organ dysfunction (PIRO). FURTHER READING Poxon V A, Keighley M R B, Dykes P W et al. Comparison of minimal and conventional surgery in patients with bleeding peptic ulcer: a multicentre trial. Br J Surg 1991; 78(11): 1344–5. Rockall T A, Logan R F A, Devlin H B et al. Incidence and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJJ 1995; 311(6999): 222–6. Rollhauser C, Fleischer D E. Nonvariceal upper gastrointestinal bleeding. Endoscopy 2002; 34(2): 111–18.
FOUNDATION YEARS 1:2
Nicoletta Zimblerr is a Consultant Anaesthetist at the London Chest Hospital, UK. Anne Campbell is a Consultant Anaesthetist at Heart Hospital, University College London Hospital, London, UK.
32
© 2005 The Medicine Publishing Company Ltd
ORGAN FAILURE
Haemodynamic and laboratory parameters suggestive of sepsis
Definitions of sepsis Term Bacteraemia
Definition Presence of bacteria in blood
Sepsis
Patients having an inflammatory response with documented infection
Septic shock
Hypotension not responsive to adequate fluid resuscitation with hypoperfusion or organ dysfunction
SIRS
Systemic response to include 2 or more abnormalities in temperature, heart rate, respiratory rate and white blood cell count
MODS
Two or more organ dysfunction
Ð Systemic vascular resistance and Ï cardiac output Ï Oxygen consumption Leukocytosis/neutropenia Lactic acidosis Impaired renal functionl/liver dysfunction Thrombocytopenia/disseminated intravascular coagulation Ï Procalcitonin Ï Cytokines/C-reactive protein
3
Microbiology: making a microbiological diagnosis in sepsis is important to ensure that effective antimicrobial therapy is given and to provide information for the local microbiology database to assist with empirical prescribing. There are marked differences between ICUs in their microbial ecology, including the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). Antimicrobial resistance patterns also vary widely (e.g. penicillin resistance in Streptococcus pneumoniae, e gentamicin resistance in Enterobacter spp). Blood cultures are positive in one-third of sepsis cases. Gram-positive and Gram-negative infections occur with equal frequency. Mixed bacterial infections are less common (< 10% of cases in the UK). Gram-positive infections are usually caused by staphylococci (both Staphylococcus aureus and coagulase-negative staphylococci), but are also caused by enterococci and pneumococci. Most Gram-negative infections are caused by Enterobacter spp. (usually Escherichia coli and Klebsiella), although pseudomonas is another likely pathogen. Candidiasis is the cause of sepsis in 5% of cases in the UK.
Source: Levy M M, Fink M P, Marshall J C et al. 2001 SCCM/ESICM/ACCP/ ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29: 530–8.
1
Investigations Clinical and laboratory diagnosis of sepsis The clinical signs are listed in Figure 2. The haemodynamic and laboratory parameters that suggest sepsis are shown in Figure 3. Biological markers of infection The early detection of sepsis is difficult. The early signs of sepsis may be similar to those of various non-infectious processes. In addition, culture results may not be immediately available. A component of the inflammatory response is the release of cytokines and acute phase proteins which rapidly increase in the serum. The principal cytokines (tumour necrosis factor-alpha TNFalpha, interleukin-1 IL-1, IL-6, IL-8, IL-10) increase during sepsis. However, they also increase in non-bacterial infections (e.g. malaria), burns, trauma and pancreatitis. Acute phase proteins (e.g. C-reactive protein) and procalcitonin are useful in differentiating conditions that mimic sepsis; their levels are usually significantly higher in bacterial infections than in viral or inflammatory conditions.
Non-infective causes of SIRS
Diagnosis of infection Sepsis can complicate infection occurring at any site, but the respiratory tract, abdomen and blood stream are commonly affected.
Tissue injury
Surgery/trauma Haematoma/venous thrombosis Myocardial/pulmonary infarction Pancreatitis
Metabolic
Thyroid storm Acute adrenal insufficiency
Drug-related
Blood products Cytokines (e.g. granulocyte macrophage colony stimulating factor) Malignant hyperpyrexia due to anaesthetic agents Neuroleptic malignant syndrome
Malignancy
Tumour lysis syndrome Hypernephroma/lymphoma
Neurological
Subarachnoid haemorrhage
Clinical signs of sepsis • • • • • •
Fever/hypothermia Tachycardia Tachypnoea Signs of peripheral vasodilatation Shock Agitation, confusion, decreased level of consciousness 4
2
FOUNDATION YEARS 1:2
33
© 2005 The Medicine Publishing Company Ltd
ORGAN FAILURE
Excluding non-infective causes of SIRS: establishing that the patient has an infective cause of SIRS can be difficult, and may be best carried out by eliminating non-infective causes (Figure 4).
The diagnosis of intra-abdominal infection is made using ultrasonography or CT (CT is more useful than ultrasonography in evaluating the retroperitoneum). Wherever possible, percutaneous drainage of intra-abdominal abscesses is useful. Laparotomy should be reserved for those cases where: • there are no well-defined collections • dead tissue requires debridement • residual collections cannot be drained percutaneously.
Localizing the site and source of infection can be difficult, due to the multiple pathological processes present and the use of antibiotics preventing microbiological diagnoses. Fever is a common sign in hospitalized patients and may be the first indicator of sepsis. Clinical examination guided by risk factors relevant to the individual patient is essential, and should direct subsequent investigations. Wounds caused by surgery or trauma should be examined for signs of infection. Attention should be paid to sites of vascular access for signs of phlebitis or cellulitis, and to central venous catheters for signs of infection. Pressure areas or injection sites should be observed for evidence of infection of soft tissue. Fundoscopy should be performed to identify candidal endophthalmitis. Occasionally, the site of infection is occult (e.g. sinusitis, deep intra-abdominal infection). Urine should be cultured and examined microscopically, diarrhoea should be tested for Clostridium difficile. Ventilator-associated pneumonia is common, but difficult to diagnose. Less common causes of sepsis (e.g. acalculous cholecystitis, candidiasis) should always be considered.
Haemodynamic therapy Shock is the alteration of tissue perfusion, with a reduction in the delivery of oxygen and other nutrients to the tissues, causing cellular, and then organ, dysfunction. The goals of haemodynamic therapy are to restore effective tissue perfusion and therefore normalize cellular function. In sepsis, abnormal distribution of a normal or increased cardiac output and abnormal control of the microvasculature result in impaired tissue perfusion and cellular damage. The resulting inflammatory response involves many mediators (e.g. nitric oxide). Hence, the endpoints of therapy are more difficult to define than in other forms of shock, where a reduction of blood flow is the main problem. Septic shock is characterized by hypotension (in adults, a mean arterial pressure of < 65–70 mmHg) and is characterized by oliguria, reduced capillary refill and confusion. Adequacy of tissue perfusion can be assessed by evaluating coagulation, renal function, liver function and gut perfusion.
Management Antibiotics The use of pre-emptive broad-spectrum antibiotics is essential in the management of sepsis. The drainage of abcesses and the removal of foreign material or necrotic tissue are also extremely important. The Gram stain and the primary site of infection are the two most important factors in determining the choice of antibiotic therapy (see above). Early administration of appropriate antibiotics reduces mortality in sepsis. Furthermore, administration of two antibiotics may improve outcome further by: • broadening the antibacterial spectrum • treating polymicrobial infections, which are more likely in infections of the abdomen and pelvis • acting synergistically (resulting in enhanced antibacterial activity) • reducing the emergence of resistant bacteria. Severe sepsis and MODS may be treated by monotherapy with imipenem or meropenem. This is as effective as combination therapy with two antibiotics and is less toxic.
Mixed venous oxygen saturation (SvO2) can be measured in patients who have a pulmonary artery catheter in situ. SvO2 is dependent on cardiac output, oxygen demand, haemoglobin and arterial oxygen saturation. SvO2 is usually 70–75%, but can be elevated in sepsis due to maldistribution of blood flow. Levels of lactate in blood are usually raised in sepsis, secondary to anaerobic metabolism due to hypoperfusion or from decreased clearance by the liver. Fluid resuscitation: the goal of fluid resuscitation is restoration of tissue perfusion. Volume replacement results in increased cardiac output and oxygen delivery. Fluid challenges should be titrated to clinical endpoints of blood pressure, heart rate, urine output and central venous pressure. Sepsis is associated with hypovolaemia. This may be relative, due to vasodilation and peripheral blood pooling. Thus, the initial phase of sepsis presents with low cardiac output and low filling pressures. The hyperdynamic state becomes apparent only after volume repletion. The choice of fluid for resuscitation may not be important, but haemoglobin should be maintained at > 8 g/dl.
Surgery Radiological and surgical procedures to control the source of an infection should be undertaken only after stabilization, although resuscitation should proceed as rapidly as possible. However, in sepsis associated with some conditions (e.g. intestinal infarction), haemodynamic stabilization (see below) is not possible until the rapidly advancing tissue necrosis has been stopped. In necrotizing fasciitis, delayed and incomplete debridement results in increased mortality. The decision to intervene surgically in infected pancreatic necrosis should be delayed in the stable patient to permit adequate demarcation of tissue planes.
FOUNDATION YEARS 1:2
Vasopressor therapy should be started when fluid resuscitation fails to restore organ perfusion. An arterial catheter for continuous monitoring of blood pressure should be used. A mean arterial pressure < 60 mmHg is associated with compromised autoregulation in coronary, renal and cerebral vascular beds; elderly patients require higher pressures to maintain adequate perfusion. Norepinephrine and dopamine are first-line treatment to correct hypotension in septic shock.
34
© 2005 The Medicine Publishing Company Ltd
ORGAN FAILURE
The coagulation and fibrinolytic system in disseminated intravascular coagulation (DIC) Cytokines Mononuclear cells
Natural anticoagulant pathways (all depressed in DIC)
Endothelial cells
Tissue factors + Factor VIIa
Factor IX Factor IXa
Tissue factor pathway inhibitor
Protein C +S
Factor Xa Factor V
Factor X Antithrombin III
Cytokines Prothrombin
Plasminogen
Thrombin
Plasminogen activator inhibitor-1
Fibrinogen
Fibrin Plasmin Fibrin degradation
5
Inotropic therapy is not straightforward. Epinephrine increases blood pressure in patients unresponsive to other agents, but its negative effects on gastric flow and effect on lactate levels in blood suggest its use should be limited.
Patients also require less prolonged mechanical ventilation and renal replacement therapy.
Other supportive therapies Patients who survive circulatory and organ failure in sepsis may suffer complications such as pulmonary embolism and bleeding from stress ulcers, and it is important to give effective prophylaxis. Catabolism associated with sepsis influences recovery, and can compromise the immune response to infection. Early and adequate enteral nutritional support is therefore important.
Adult respiratory distress syndrome (ARDS) When the clinical signs of sepsis first appear, more than one-third of patients meet the criteria for ARDS. ARDS is characterized by an acute onset of hypoxia and radiographical evidence of bilateral infiltrates (without evidence of fluid overload). Management involves the treatment of the underlying cause and support of the respiratory system. Death from refractory respiratory failure is uncommon; the most common cause of death is multiple-organ failure or recurrent sepsis. A small proportion of patients will subsequently develop lung fibrosis, and it is not clear whether treatment with corticosteroids improves outcome in these cases.
Complications
Recent advances in the treatment of sepsis Recombinant human-activated protein (APC): in 2001, results of the PROWESS clinical trial were published, which suggested a significant reduction in mortality in sepsis cases who were treated with APC. This was the first time the importance of the coagulation cascade in causing sepsis had been addressed. When APC binds with protein S, anti-inflammatory, anticoagulatory, and profibrinolytic actions are triggered (Figure 5).
FURTHER READING Fry D E. Sepsis syndrome. Am Surg 2000; 66: 126–32. Levy M, Fink M P, Marshall J C et al. 2001 SCCM/ESICM/ACCP/ATS/ SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29: 530–8. Marshall J C. SIRS and MODS: what is their relevance to the science and practice of intensive care? Shockk 2000; 14: 586–9.
Corticosteroids: adrenocortical function is insufficient in sepsis. Recent studies suggest that using low doses of corticosteroids to treat sepsis markedly reduces the doses of vasopressors used and significantly reduces mortality. Insulin: tight control of blood glucose (<6.1 mmol/l) significantly reduces mortality in sepsis, especially in severe sepsis and MODS.
FOUNDATION YEARS 1:2
35
© 2005 The Medicine Publishing Company Ltd
(Pauchet’s manoeuvre) is indicated. Formal total gastrectomy may be unnecessary. High lesser curve ulcers can be treated by direct ulcer excision (not a minor procedure). Surgical therapy for any patient with refractory variceal bleeding represents a significant risk. Schaefer proposes the following good practice guidelines for assessing surgical candidacy. • All patients should have received a diagnostic and at least one therapeutic attempt at haemostasis. • Surgical candidates should include those with failed haemostasis after vigorous resuscitation or those with clinically significant re-bleeding after 12–24 hours of initial haemostasis. • Prohibitive surgical risk: Childs class C. In advanced liver disease, transplantation is the management of choice, but donation yield remains the rate-limiting factor. Transplantation is the optimal portal decompressive shunt and has the advantage of restoring synthetic liver function. The recent 1- and 5-year survival rates are 80% and 60% respectively.
Sepsis, SIRS and MODS Nicoletta Zimbler Anne Campbell
Sepsis, systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) represent progressive stages of the same illness, in which a systemic response to an infection may lead to a generalized inflammatory reaction in organs remote from the initial insult and eventually to end-organ failure. Sepsis is the most common cause of death in the intensive care unit (ICU) and the mortality rate is > 50% in most centres in the UK.
Definitions of sepsis In the past, the terms bacteraemia, septicaemia, sepsis, sepsis syndrome and septic shock were all used to define sepsis, which led to an imprecise understanding of sepsis and its related disorders, and to confusion in the interpretation of clinical trials. In 1991, a new set of definitions were introduced by the Consensus Conference of the American College of Chest Physicians and the Society of Critical Care Medicine (USA). They included bacteraemia, sepsis, septic shock, SIRS and MODS in their definitions (Figure 1). SIRS describes the widespread inflammation that occurs following a wide variety of insults (e.g. infection, pancreatitis, trauma, burns), and hence introduces a concept that endogenous mediators of inflammation play an important role in sepsis. The terms septicaemia, sepsis syndrome, and refractory shock were eliminated by the conference because they are nonspecific. Ten years later, the International Sepsis Definitions Conference tried to change the definition of sepsis. The molecular pathogenesis of sepsis is better understood, but very few studies have produced useful conclusions. One of the major problems in research is the heterogeneity of patients and the problems of trying to make groups of patients comparable. A new staging system for sepsis may be introduced by the International Sepsis Definitions Conference that will include information on predisposing factors, infection, host response and organ dysfunction (PIRO). FURTHER READING Poxon V A, Keighley M R B, Dykes P W et al. Comparison of minimal and conventional surgery in patients with bleeding peptic ulcer: a multicentre trial. Br J Surg 1991; 78(11): 1344–5. Rockall T A, Logan R F A, Devlin H B et al. Incidence and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJJ 1995; 311(6999): 222–6. Rollhauser C, Fleischer D E. Nonvariceal upper gastrointestinal bleeding. Endoscopy 2002; 34(2): 111–18.
FOUNDATION YEARS 1:2
Nicoletta Zimblerr is a Consultant Anaesthetist at the London Chest Hospital, UK. Anne Campbell is a Consultant Anaesthetist at Heart Hospital, University College London Hospital, London, UK.
32
© 2005 The Medicine Publishing Company Ltd
ORGAN FAILURE
Haemodynamic and laboratory parameters suggestive of sepsis
Definitions of sepsis Term Bacteraemia
Definition Presence of bacteria in blood
Sepsis
Patients having an inflammatory response with documented infection
Septic shock
Hypotension not responsive to adequate fluid resuscitation with hypoperfusion or organ dysfunction
SIRS
Systemic response to include 2 or more abnormalities in temperature, heart rate, respiratory rate and white blood cell count
MODS
Two or more organ dysfunction
Ð Systemic vascular resistance and Ï cardiac output Ï Oxygen consumption Leukocytosis/neutropenia Lactic acidosis Impaired renal functionl/liver dysfunction Thrombocytopenia/disseminated intravascular coagulation Ï Procalcitonin Ï Cytokines/C-reactive protein
3
Microbiology: making a microbiological diagnosis in sepsis is important to ensure that effective antimicrobial therapy is given and to provide information for the local microbiology database to assist with empirical prescribing. There are marked differences between ICUs in their microbial ecology, including the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). Antimicrobial resistance patterns also vary widely (e.g. penicillin resistance in Streptococcus pneumoniae, e gentamicin resistance in Enterobacter spp). Blood cultures are positive in one-third of sepsis cases. Gram-positive and Gram-negative infections occur with equal frequency. Mixed bacterial infections are less common (< 10% of cases in the UK). Gram-positive infections are usually caused by staphylococci (both Staphylococcus aureus and coagulase-negative staphylococci), but are also caused by enterococci and pneumococci. Most Gram-negative infections are caused by Enterobacter spp. (usually Escherichia coli and Klebsiella), although pseudomonas is another likely pathogen. Candidiasis is the cause of sepsis in 5% of cases in the UK.
Source: Levy M M, Fink M P, Marshall J C et al. 2001 SCCM/ESICM/ACCP/ ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29: 530–8.
1
Investigations Clinical and laboratory diagnosis of sepsis The clinical signs are listed in Figure 2. The haemodynamic and laboratory parameters that suggest sepsis are shown in Figure 3. Biological markers of infection The early detection of sepsis is difficult. The early signs of sepsis may be similar to those of various non-infectious processes. In addition, culture results may not be immediately available. A component of the inflammatory response is the release of cytokines and acute phase proteins which rapidly increase in the serum. The principal cytokines (tumour necrosis factor-alpha TNFalpha, interleukin-1 IL-1, IL-6, IL-8, IL-10) increase during sepsis. However, they also increase in non-bacterial infections (e.g. malaria), burns, trauma and pancreatitis. Acute phase proteins (e.g. C-reactive protein) and procalcitonin are useful in differentiating conditions that mimic sepsis; their levels are usually significantly higher in bacterial infections than in viral or inflammatory conditions.
Non-infective causes of SIRS
Diagnosis of infection Sepsis can complicate infection occurring at any site, but the respiratory tract, abdomen and blood stream are commonly affected.
Tissue injury
Surgery/trauma Haematoma/venous thrombosis Myocardial/pulmonary infarction Pancreatitis
Metabolic
Thyroid storm Acute adrenal insufficiency
Drug-related
Blood products Cytokines (e.g. granulocyte macrophage colony stimulating factor) Malignant hyperpyrexia due to anaesthetic agents Neuroleptic malignant syndrome
Malignancy
Tumour lysis syndrome Hypernephroma/lymphoma
Neurological
Subarachnoid haemorrhage
Clinical signs of sepsis • • • • • •
Fever/hypothermia Tachycardia Tachypnoea Signs of peripheral vasodilatation Shock Agitation, confusion, decreased level of consciousness 4
2
FOUNDATION YEARS 1:2
33
© 2005 The Medicine Publishing Company Ltd
ORGAN FAILURE
Excluding non-infective causes of SIRS: establishing that the patient has an infective cause of SIRS can be difficult, and may be best carried out by eliminating non-infective causes (Figure 4).
The diagnosis of intra-abdominal infection is made using ultrasonography or CT (CT is more useful than ultrasonography in evaluating the retroperitoneum). Wherever possible, percutaneous drainage of intra-abdominal abscesses is useful. Laparotomy should be reserved for those cases where: • there are no well-defined collections • dead tissue requires debridement • residual collections cannot be drained percutaneously.
Localizing the site and source of infection can be difficult, due to the multiple pathological processes present and the use of antibiotics preventing microbiological diagnoses. Fever is a common sign in hospitalized patients and may be the first indicator of sepsis. Clinical examination guided by risk factors relevant to the individual patient is essential, and should direct subsequent investigations. Wounds caused by surgery or trauma should be examined for signs of infection. Attention should be paid to sites of vascular access for signs of phlebitis or cellulitis, and to central venous catheters for signs of infection. Pressure areas or injection sites should be observed for evidence of infection of soft tissue. Fundoscopy should be performed to identify candidal endophthalmitis. Occasionally, the site of infection is occult (e.g. sinusitis, deep intra-abdominal infection). Urine should be cultured and examined microscopically, diarrhoea should be tested for Clostridium difficile. Ventilator-associated pneumonia is common, but difficult to diagnose. Less common causes of sepsis (e.g. acalculous cholecystitis, candidiasis) should always be considered.
Haemodynamic therapy Shock is the alteration of tissue perfusion, with a reduction in the delivery of oxygen and other nutrients to the tissues, causing cellular, and then organ, dysfunction. The goals of haemodynamic therapy are to restore effective tissue perfusion and therefore normalize cellular function. In sepsis, abnormal distribution of a normal or increased cardiac output and abnormal control of the microvasculature result in impaired tissue perfusion and cellular damage. The resulting inflammatory response involves many mediators (e.g. nitric oxide). Hence, the endpoints of therapy are more difficult to define than in other forms of shock, where a reduction of blood flow is the main problem. Septic shock is characterized by hypotension (in adults, a mean arterial pressure of < 65–70 mmHg) and is characterized by oliguria, reduced capillary refill and confusion. Adequacy of tissue perfusion can be assessed by evaluating coagulation, renal function, liver function and gut perfusion.
Management Antibiotics The use of pre-emptive broad-spectrum antibiotics is essential in the management of sepsis. The drainage of abcesses and the removal of foreign material or necrotic tissue are also extremely important. The Gram stain and the primary site of infection are the two most important factors in determining the choice of antibiotic therapy (see above). Early administration of appropriate antibiotics reduces mortality in sepsis. Furthermore, administration of two antibiotics may improve outcome further by: • broadening the antibacterial spectrum • treating polymicrobial infections, which are more likely in infections of the abdomen and pelvis • acting synergistically (resulting in enhanced antibacterial activity) • reducing the emergence of resistant bacteria. Severe sepsis and MODS may be treated by monotherapy with imipenem or meropenem. This is as effective as combination therapy with two antibiotics and is less toxic.
Mixed venous oxygen saturation (SvO2) can be measured in patients who have a pulmonary artery catheter in situ. SvO2 is dependent on cardiac output, oxygen demand, haemoglobin and arterial oxygen saturation. SvO2 is usually 70–75%, but can be elevated in sepsis due to maldistribution of blood flow. Levels of lactate in blood are usually raised in sepsis, secondary to anaerobic metabolism due to hypoperfusion or from decreased clearance by the liver. Fluid resuscitation: the goal of fluid resuscitation is restoration of tissue perfusion. Volume replacement results in increased cardiac output and oxygen delivery. Fluid challenges should be titrated to clinical endpoints of blood pressure, heart rate, urine output and central venous pressure. Sepsis is associated with hypovolaemia. This may be relative, due to vasodilation and peripheral blood pooling. Thus, the initial phase of sepsis presents with low cardiac output and low filling pressures. The hyperdynamic state becomes apparent only after volume repletion. The choice of fluid for resuscitation may not be important, but haemoglobin should be maintained at > 8 g/dl.
Surgery Radiological and surgical procedures to control the source of an infection should be undertaken only after stabilization, although resuscitation should proceed as rapidly as possible. However, in sepsis associated with some conditions (e.g. intestinal infarction), haemodynamic stabilization (see below) is not possible until the rapidly advancing tissue necrosis has been stopped. In necrotizing fasciitis, delayed and incomplete debridement results in increased mortality. The decision to intervene surgically in infected pancreatic necrosis should be delayed in the stable patient to permit adequate demarcation of tissue planes.
FOUNDATION YEARS 1:2
Vasopressor therapy should be started when fluid resuscitation fails to restore organ perfusion. An arterial catheter for continuous monitoring of blood pressure should be used. A mean arterial pressure < 60 mmHg is associated with compromised autoregulation in coronary, renal and cerebral vascular beds; elderly patients require higher pressures to maintain adequate perfusion. Norepinephrine and dopamine are first-line treatment to correct hypotension in septic shock.
34
© 2005 The Medicine Publishing Company Ltd
ORGAN FAILURE
The coagulation and fibrinolytic system in disseminated intravascular coagulation (DIC) Cytokines Mononuclear cells
Natural anticoagulant pathways (all depressed in DIC)
Endothelial cells
Tissue factors + Factor VIIa
Factor IX Factor IXa
Tissue factor pathway inhibitor
Protein C +S
Factor Xa Factor V
Factor X Antithrombin III
Cytokines Prothrombin
Plasminogen
Thrombin
Plasminogen activator inhibitor-1
Fibrinogen
Fibrin Plasmin Fibrin degradation
5
Inotropic therapy is not straightforward. Epinephrine increases blood pressure in patients unresponsive to other agents, but its negative effects on gastric flow and effect on lactate levels in blood suggest its use should be limited.
Patients also require less prolonged mechanical ventilation and renal replacement therapy.
Other supportive therapies Patients who survive circulatory and organ failure in sepsis may suffer complications such as pulmonary embolism and bleeding from stress ulcers, and it is important to give effective prophylaxis. Catabolism associated with sepsis influences recovery, and can compromise the immune response to infection. Early and adequate enteral nutritional support is therefore important.
Adult respiratory distress syndrome (ARDS) When the clinical signs of sepsis first appear, more than one-third of patients meet the criteria for ARDS. ARDS is characterized by an acute onset of hypoxia and radiographical evidence of bilateral infiltrates (without evidence of fluid overload). Management involves the treatment of the underlying cause and support of the respiratory system. Death from refractory respiratory failure is uncommon; the most common cause of death is multiple-organ failure or recurrent sepsis. A small proportion of patients will subsequently develop lung fibrosis, and it is not clear whether treatment with corticosteroids improves outcome in these cases.
Complications
Recent advances in the treatment of sepsis Recombinant human-activated protein (APC): in 2001, results of the PROWESS clinical trial were published, which suggested a significant reduction in mortality in sepsis cases who were treated with APC. This was the first time the importance of the coagulation cascade in causing sepsis had been addressed. When APC binds with protein S, anti-inflammatory, anticoagulatory, and profibrinolytic actions are triggered (Figure 5).
FURTHER READING Fry D E. Sepsis syndrome. Am Surg 2000; 66: 126–32. Levy M, Fink M P, Marshall J C et al. 2001 SCCM/ESICM/ACCP/ATS/ SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29: 530–8. Marshall J C. SIRS and MODS: what is their relevance to the science and practice of intensive care? Shockk 2000; 14: 586–9.
Corticosteroids: adrenocortical function is insufficient in sepsis. Recent studies suggest that using low doses of corticosteroids to treat sepsis markedly reduces the doses of vasopressors used and significantly reduces mortality. Insulin: tight control of blood glucose (<6.1 mmol/l) significantly reduces mortality in sepsis, especially in severe sepsis and MODS.
FOUNDATION YEARS 1:2
35
© 2005 The Medicine Publishing Company Ltd