Sepsis, SIRS and MODS - Surgery 2009


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Sepsis, SIRS and MODS - Surgery 2009

Ben Griffiths and Iain D Anderson

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Sepsis, SIRS and MODS - Surgery 2009

  1. 1. INFECTION Sepsis, SIRS and MODS Severe sepsis: Sepsis with evidence of organ dysfunction or tissue hypoperfusion. Ben Griffiths Septic shock: Sepsis-induced hypotension which persists despite adequate fluid resuscitation. Iain D Anderson Multiple Organ Dysfunction Syndrome (MODS): the failure of two, or more, organs which are unable to maintain homeostasis without intervention. SIRS is triggered by an insult to the body which may be ischaemic, inflammatory, traumatic or infective. In healthy individuals the neuroendocrine and immune systems combine to eradicate the insult, resulting in resolution, but if this local control fails then the patient can progress down the sepsis pathway. The inflammatory cascade is a complex process that involves humoral and cellular responses, complement and cytokine cascades. Important mediators include platelet-activating factor (PAF), tumour necrosis factor alpha (TNFa) and the interleukins 1, 6, 8 and 10. SIRS may be seen in emergency admissions but is also often seen in ward patients who have developed a complication. In the UK, many wards now use an early warning score system (EWS) to identify patients with abnormal physiology and there is some overlap with SIRS criteria enabling clinical staff to rapidly target patients at risk. We recommend a structured approach as outlined in CCrISP,1 to facilitate early identification, rapidly restore normal physiology and halt progression. While simple cases may be resolved by prescribing oxygen, a fluid bolus and antibiotics, many are more complex. Should the patient fail to improve quickly or deteriorate, then senior members of the surgical team should be informed and the critical care team alerted. In complex patients several episodes of SIRS or sepsis are expected and the structured approach should be employed over and over again to avoid important omissions. The most common cause of sepsis is bacterial infection but viruses, fungi and parasites should always be considered. The most common sites are chest, abdomen, genitourinary tract and infected intravascular lines. Emergency cases, operations involving contaminated sites and patients with co-morbidities are also more likely victims. While milder sepsis often responds to simple treatments, deterioration is unpredictable and mortality from severe sepsis remains high (28e50%) e the Surviving Sepsis Campaign (international consensus group) guidelines2 are now widely used to reduce this. They provide evidence-based ‘care bundles’ which should be delivered expediently to septic patients as outlined below, Table 1. These targets emphasize the importance of speed: failure to achieve them is associated with poor outcome. Some steps require critical care unit management. Patients should always be managed in an appropriate area but waiting for transfer should not delay the commencement of necessary treatment. Abstract Sepsis, a systemic inflammatory process triggered by infection, is the commonest mode of death in modern surgical practice. Sepsis exists as a spectrum of severity from the Systemic Inflammatory Response Syndrome (SIRS) through to Multiple Organ Dysfunction Syndrome (MODS). The surgeon must be able to recognize patients within this spectrum rapidly because early identification and intervention is the key to reducing mortality. Rapid, accurate assessment and management are facilitated by using a structured approach such as that described in the Care of the Critically-Ill Surgical Patient (CCrISP) programme. Control of the source of sepsis is fundamental to success and this should be led by senior surgeons. Key steps and timelines are described in the evidence-based ‘care bundles’ of the Surviving Sepsis Campaign. Keywords resuscitation; source control; sepsis; SIRS; MODS Sepsis is a major cause of morbidity and mortality worldwide with around 36,800 sepsis-related deaths in the UK per annum. Only coronary heart disease kills more people in the UK and it is anticipated that worldwide rates of sepsis will increase year on year. Sepsis is the leading mechanism of death in modern surgical practice and the surgeon must understand common definitions and their place in the sepsis spectrum. SIRS is extremely common and patients will be seen with this on most ward rounds. The surgeon should aim to identify cases early by conducting structured ward rounds (progress/history, examination, observations, laboratory results) with the aim of preventing the slide of a patient with SIRS on the surgical ward to a critically-ill patient with MODS on ICU. This slippery slope from SIRS to MODS can be rapid and difficult to halt but the earlier the intervention the better the outcome. Systemic Inflammatory Response Syndrome (SIRS) d can be diagnosed when any two of the following criteria exist: body temperature 36 C or 38 C heart rate 90 beats/min respiratory rate 20 breaths/min or PCO2 4.3 kPa (32 mmHg) white cell count 4 or 12 Â 109/l OR the presence of greater than 10% immature neutrophils. Sepsis: SIRS in the presence of infection, either proven or suspected. Ben Griffiths FRCS is a Specialist Registrar in General Surgery on the North-West England rotation, UK. Conflict of interests: none declared. Serum lactate Serum lactate is produced by anaerobic metabolism and is a marker of tissue hypoperfusion. It helps to identify inadequate oxygen delivery and has prognostic value for patients in septic shock. Iain D Anderson FRCS is a Consultant Colorectal Surgeon at the Intestinal Failure Unit, Salford Royal Hospital, Salford, UK. Conflict of interests: none declared. SURGERY 27:10 446 Ó 2009 Elsevier Ltd. All rights reserved.
  2. 2. INFECTION Next steps in management Sepsis resuscitation bundle Source control After resuscitation, controlling the source of sepsis is essential to halting progress down the sepsis slope. Experienced surgical input is needed to lead the search for the source of sepsis and arrange urgent control. This may involve appropriate imaging if the site is not obvious or immediate intervention once the source has been identified (see Table 2). Source control may simply involve removal of an in-dwelling vascular or urinary catheter or a course of appropriate antibiotics. Radiologically-guided drainage is a minimally invasive technique used to drain suitable solitary intra-abdominal/pelvic abscesses. Clearly, in a patient with perforated diverticular disease and faecal peritonitis the only effective method of source control will be an urgent laparotomy and definitive surgical management of the source is the gold standard. However, a limited damage control laparotomy may occasionally be necessary for rapid control of sepsis in a patient too ill (acidotic, coagulopathic) to survive complex definitive surgery. The patient returns to the ICU for physiological improvement before delayed definitive surgery. The goal is to perform all indicated tasks within the first 6 h of identification of severe sepsis in all patients.The tasks are: 1. Measure serum lactate 2. Obtain blood cultures prior to antibiotic administration 3. Administer broad-spectrum antibiotic, within 3 h of emergency admission and within 1 h otherwise 4. In the event of hypotension and/or a serum lactate 4 mmol/l a. Deliver an initial minimum of 20 ml/kg of crystalloid or an equivalent b. Apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) 65 mmHg 5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or lactate 4 mmol/l a. Achieve a central venous pressure (CVP) of 8 mmHg b. Achieve a central venous oxygen saturation (ScvO2) 70 % or mixed venous oxygen saturation (SvO2) 65% (Reproduced with permission. Copyright 2008. European Society of Intensive Care Medicine, International Sepsis Forum and Society of Critical Care Medicine.) Nutrition Nutrition should be considered as part of every definitive management plan. All septic patients are catabolic and their calorie requirement increases significantly. The enteral route should be utilized wherever possible and this may involve accessing the gastrointestinal tract by tube (typically nasogastric/ nasojejunal tube, or radiological or open gastrostomy/jejunostomy). The enteral route also maintains mucosal integrity and may protect against further septic complications originating from the gut, through colonisation/translocation, but if unavailable, then parenteral nutrition should be used with meticulous care of central venous catheters to prevent further sepsis. Immuno-modulating feeds containing immunonutrients such as arginine, glutamine, and omega-3 fatty acids are conceptually appealing but data from multiple individual trials and several meta-analyses have failed to produce convincing evidence of general benefit. Table 1 Intravenous fluid and vasopressors If the serum lactate is 4 mmol/l (or the patient is underperfused) then an intravenous fluid bolus of 20 ml/kg crystalloid should be given rapidly and the response evaluated. Crystalloid or colloid can be used as there is no evidence that one is superior to the other, but 5% dextrose should be avoided. In patients unresponsive to fluid challenges, vasopressors should be started to aim at a mean arterial pressure (MAP) of 65 mmHg. In sepsis the most common first-line vasopressor is noradrenaline which raises MAP primarily by vasoconstriction. Goals in patients with septic shock are a central venous pressure of 8 mmHg and either a central venous oxygen saturation (ScvO2) of 70% or a mixed venous oxygen saturation (SvO2) of 65%. Source control in sepsis. Techniques Two sets of peripheral blood cultures should be taken as well as cultures from any in-dwelling vascular device. Blood cultures are positive in 30e50% of septic patients and the identification of the correct organism in these patients enables antibiotic therapy to be targeted subsequently. Urinary tract infection Cellulitis Aspiration of breast abscess Radiological paracolic abscess drainage Central venous catheter Hernia mesh excision Necrotising fasciitis Amputation gangrenous limb Colonic resection with stoma Small bowel anastomosis Stapling ends of bowel Drain pus, leave abdomen open Drainage of pus Device removal Debridement of dead tissue Definitive surgery Broad-spectrum antibiotics Give broad-spectrum antibiotics as soon as blood cultures have been sent, the choice depending on local policy. If necessary, get advice from your microbiologist. There is good evidence that outcome is improved if antibiotics are given within an hour of ward admission and within 3 h if seen in Accident and Emergency. SURGERY 27:10 Examples Antibiotics Blood cultures Damage control laparotomy Table 2 447 Ó 2009 Elsevier Ltd. All rights reserved.
  3. 3. INFECTION Prevention of complications Septic patients are at increased risk of venous thromboembolism and peptic ulceration. National Institute of Health and Clinical Excellence (NICE) guidelines recommend mechanical prophylaxis with low molecular weight heparin in patients with severe infection.3 Gastric acid suppression or preferably cytoprotective therapy is used for ulcer prophylaxis. Meticulous intravascular line care reduces line sepsis, and hand washing by medical and nursing staff reduces cross-infection. This has led to a relaxation of the acceptable range as shown in the bundle above. Critical care The critical care team should be informed of the presence of a patient with severe sepsis as early as possible to enable them to plan appropriate intervention and to decide on the appropriate level of care. They may employ the sepsis management ‘bundle’ for ICU care of severe sepsis, Table 3. Multiple organ dysfunction syndrome (MODS) Inspiratory plateau pressure goal Most septic patients need to be intubated and ventilated and approximately 50% will have either acute lung injury or acute respiratory distress syndrome (ARDS). Studies have shown that aiming for a mean inspiratory plateau pressure of 30 cm H2O improves all-cause mortality.8 Once initiated, MODS often follows a predictable clinical course, irrespective of the precipitating event. The first evidence of organ dysfunction is usually changes in the respiratory and cardiovascular systems. The resulting pulmonary failure and ensuing hypoxaemia are followed by hepatic and renal dysfunction and disorders of the haemostatic, gastrointestinal and central nervous systems. Bone marrow failure and myocardial dysfunction are usually late manifestations of MODS. Support for the failing organs is the cornerstone of modern ICU practice, and prognosis is most directly related to the number of failed organs. Mortality from septic shock approaches 50% and each subsequent failing organ probably adds a further 15% to that figure. In surgical patients with MODS, source control is vital for success. Additionally, each failing organ has to be supported. Steroid therapy Intravenous corticosteroids (hydrocortisone 200e300 mg/day, for 7 days in divided doses or by infusion) are recommended in patients with septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain adequate blood pressure. A meta-analysis has shown significant reductions in ICU and all-cause mortality as well as numbers of patients whose septic shock was reversed.4 Activated protein C (APC) APC has anticoagulant, anti-inflammatory and fibrinolytic properties. It is used in patients with severe sepsis and multiple organ dysfunction in addition to standard care. Its anticoagulant action means it is contraindicated in patients with a risk of significant bleeding. The PROWESS study5 demonstrated a 6.1% absolute reduction in 28-day mortality using recombinant human activated protein C in patients with severe sepsis and a recent Canadian study has shown improved mortality if activated protein C was given within the first 24 h of developing sepsis-induced organ dysfunction.6 NICE has recommended APC for patients with severe sepsis and organ failure. Cardiovascular Significant derangement in autoregulation of circulation is typical of sepsis. Vasoactive mediators cause vasodilatation and increase the microvascular permeability, resulting in oedema. Myocardial depression is a late feature of septic shock. Treatments include adequate volume replacement and optimisation of haemodynamic parameters using vasoactive drugs (inotropes, vasoconstrictors, vasodilators). Lungs Endothelial injury and neutrophil entrapment in the alveoli lead to local injury, disturbed capillary blood flow and enhanced microvascular permeability, resulting in interstitial and alveolar oedema. Acute lung injury and acute respiratory distress syndrome (ARDS) are a frequent manifestation of these effects. Ventilatory techniques aim to optimize oxygenation whilst preventing trauma to the lungs. Glycaemic control Hyperglycaemia is common in septic patients and there is evidence that maintaining blood glucose levels within a very tight range (4.4e6.1 mmol/l) reduces morbidity and mortality in critically-ill surgical patients.7 Maintaining glucose in such a tight range is difficult and hypoglycaemic events are more common. Sepsis management bundle Efforts to accomplish these goals should begin immediately, but these items may be completed within 24 h of presentation for patients with severe sepsis or septic shock 1. Administer low-dose steroids for septic shock by a standardized ICU policy. 2. Administer human recombinant activated protein C by a standardized ICU policy. 3. Maintain glucose control 3.9 mmol/l, but 8.3 mmol/l. 4. Maintain a median inspiratory plateau pressure (IPP) 30 cm H2O (22.8 mmHg) for mechanically ventilated patients. (Reproduced with permission. Copyright 2008. European Society of Intensive Care Medicine, International Sepsis Forum and Society of Critical Care Medicine.) Table 3 SURGERY 27:10 448 Ó 2009 Elsevier Ltd. All rights reserved.
  4. 4. INFECTION Gut The GI tract may help propagate the septic process. Bacteria in the upper GI tract may be aspirated into the lungs, producing nosocomial pneumonia and this process is made worse by the necessary gastric acid suppression in critical illness. Alternatively, cytoprotective therapy with drugs such as sucralfate can be prescribed. There is evidence from animals that the normal barrier function of the gut may be affected by splanchnic hypoperfusion or reperfusion injury allowing translocation of bacteria and endotoxins into the systemic circulation. are being used more commonly in ICUs to monitor haemostasis as a dynamic process. Novel therapies It is hoped that widespread use of the evidence-based Surviving Sepsis Campaign care bundles will translate into improvements in mortality from sepsis over the next decade. Surgical advances are likely to involve minimally invasive techniques of obtaining source control. In the critical care setting there is interest in improving understanding of the genetic polymorphisms which have been shown to be important in an individual’s susceptibility and response to sepsis. There is interest in administering APC in the inhaled form to patients with ALI as there is improved oxygenation in animal models. Hydrogen sulphide has been identified as the third gaseous transmitter (after nitric oxide and carbon monoxide) and has been shown to be a signalling molecule of the cardiovascular, neurological and inflammatory systems. Animals continue to be studied in various shock models and we wait to see whether any application in humans emerges. A Liver By virtue of the role of the liver in host defence, the abnormal synthetic functions caused by liver dysfunction can contribute to both the initiation and progression of sepsis. The reticuloendothelial system of the liver acts as a first line of defence in clearing bacteria and their products; liver dysfunction leads to a spill-over these products into systemic circulation. Markers of liver synthetic function can be useful in assessing response to treatment (C-reactive protein, serum albumin). Kidneys Acute renal failure often accompanies sepsis due to acute tubular necrosis. Systemic hypotension, direct renal vasoconstriction, release of cytokines and activation of neutrophils by endotoxins and other peptides all contribute to renal injury. Treatment involves limiting ischaemic injury to the kidney, reducing iatrogenic injury (nephrotoxic medication) and the use of renal replacement therapy. Common methods of renal replacement on the ICU include continuous veno-venous haemofiltration (CVVH), continuous veno-venous diafiltration (CWHDF) and continuous veno-venous haemodialysis (CVVHD). REFERENCES 1 Anderson ID. Care of the critically ill surgical patient. Hodder Arnold: Royal College of Surgeons; 2003. p. 7e15. 2 Also available at: 3 Also available at: 4 Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids for treating severe sepsis and septic shock. Cochrane Database Syst Rev 2005; 1: CD002243. 5 Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699e709. 6 Hodder RV, Hall R, Russell JA, Fisher HN, Lee B. Early drotrecogin alpha (activated) administration in severe sepsis is associated with lower mortality: a retrospective analysis of the Canadian ENHANCE cohort. Crit Care 2009; 13: R78. 7 Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345: 1359e67. 8 The Acute Respiratory Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342: 1301e8. Central nervous system Involvement of the CNS in sepsis produces encephalopathy and peripheral neuropathy, the pathogeneses being poorly understood. Coagulation Subclinical coagulopathy signified by a mild elevation of the thrombin or activated partial thromboplastin time (APTT) or a moderate reduction in platelet count is extremely common, but overt disseminated intravascular coagulation (DIC), with a diagnostic rise in D-dimers, is less common. Thromboelastograms SURGERY 27:10 449 Ó 2009 Elsevier Ltd. All rights reserved.