British Journal of Anaesthesia 105 (6): 734–43 (2010) Advance Access publication 27 October 2010 . doi:10.

1093/bja/aeq305

REVIEW ARTICLE

Anaesthetic management of patients with severe sepsis
D. Eissa, E. G. Carton and D. J. Buggy *
Division of Anaesthesia, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland * Corresponding author. E-mail: donal.buggy@nbsp.ie, dbuggy@mater.ie

Key points
† Patients with sepsis often require surgical interventions. † Anaesthesia can be hazardous in these cardiovascularly unstable patients. † Preoperative optimization and intraoperative and postoperative care need to be planned before starting. † Techniques that preserve cardiovascular and respiratory function are required.

Summary. Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome. Keywords: anaesthesia; emergency service; anaesthesia, general; infection; surgery; perioperative period

Epidemiology
Severe sepsis and septic shock are major healthcare problems with a reported incidence of 66– 132 per 100 000 population in the USA and UK, respectively.1 2 In 2001, a consensus conference (Society of Critical Care Medicine, European Society of Intensive Care Medicine, American College of Chest Physicians, American Thoracic Society, and Surgical Infection Society) concluded that the basic definitions of systemic inflammatory response syndrome (SIRS), as originally described in 1992 by the American College of Chest Physicians and the Society of Critical Care Medicine,3 should remain largely unchanged4 (Table 1). Because of the limitations of the definitions of SIRS and infection, the 2001 consensus conference suggested an expanded list of possible signs of systemic inflammation that may be observed in ‘septic-looking’ patients (Table 2). Severe sepsis occurs in 1 –2% of all hospitalizations and accounts for as much as 25% of intensive care unit (ICU) bed utilization. It is common in elderly, immunecompromised, and critically ill patients and is a major

cause of death in ICUs worldwide.5 Sepsis is the second leading cause of death in non-coronary ICU patients. Mortality remains high at 30–50% despite improved care in the past 10–15 yr.1 5 6

Causes of sepsis
Severe sepsis may have infective and non-infective causes (Table 3). Infections are common and amenable to treatment; therefore, in patients presenting with clinical signs of systemic inflammation (SIRS), an infective cause should be actively sought. Community-acquired infections in previously well patients are easier to recognize than nosocomial infections in debilitated hospitalized patients. Infections leading to sepsis include central nervous system (CNS) infections, for example, meningitis or encephalitis, cardiovascular infections (e.g. infective endocarditis), respiratory infections (e.g. pneumonia), gastrointestinal infections (e.g. peritonitis), or urinary tract infections (e.g. pyelonephritis).1 7 Although bacterial infections are the most common infective cause, viruses and fungi can also cause septic shock. Non-infective

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operating theatre.1.10% immature forms SIRS with clinical evidence of infection Sepsis associated with organ dysfunction. despite fluid resuscitation. In high-risk surgical or trauma patients with sepsis. where somewhat didactic therapies are proposed in 735 . gynaecological sepsis.9 10 Surviving Sepsis Campaign Following an international process of consultation to standardize the management of critically ill septic patients.Anaesthetic management of patients with severe sepsis BJA Table 2 Diagnostic criteria for sepsis Documented or suspected infection with some of the following clinical signs or laboratory data 1. .5 ml kg21 h21) Creatinine increase (. and headache The threshold definition is two or more of the following criteria: o temperature . and the adequacy of haemodynamic resuscitation.20 ml kg21 over 24 h) Hyperglycaemia (. pancreatitis. plt count.368C o heart rate . Hyperbilirubinaemia (e) Tissue hypoperfusion parameters Lactate.12×109 litre21 or .10% immature forms C-reactive protein .3 mmol litre21 Decreased capillary refill Mottling of skin Pathophysiology of sepsis A detailed discussion of the physiology of sepsis is beyond the scope of this review. or hypoperfusion abnormalities Sepsis-induced hypotension.4 or . the Surviving Sepsis Campaign suggested that therapies be grouped or ‘bundled’ for particular subsets of patients. Preoperative assessment Although not all patients with severe sepsis have an infective focus.7. rigors.38.0.100) Absent bowel sounds Table 1 2001 sepsis definitions by the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM)3 4 Pathological entity Bacteraemia Septicaemia Definition Presence of bacteria in the bloodstream The presence of large numbers of bacteria in the bloodstream often associated with systemic signs and symptoms such as fever.90 mm Hg) SvO2 . and the organisms most commonly implicated.7 mmol litre21) in non-diabetic patients (b) Inflammatory parameters WCC . Signs of systemic inflammation (a) General parameters Fever (core temp. the pathophysiology underpinning the symptoms and signs.4. the presence of shock or multi-organ dysfunction. . recent surgery) or may be more difficult to identify (e.5.2 SD above normal value (c) Haemodynamic parameters Arterial hypotension (SAP . Anaesthetic management Anaesthetists are frequently involved in the care of severely septic patients in the emergency department.8 This review concentrates on anaesthetic management of patients with severe sepsis syndrome. is central to the successful treatment of a patient with severe sepsis.4×109 litre21 or . Infection source control. involving surgical drainage of an abscess or debridement of necrotic tissue coupled with early effective antimicrobial therapy. pulmonary embolus.12. soft tissue.40) Oliguria (. but has itself been recently reviewed comprehensively.30 bpm) Altered mental status Significant positive fluid balance (.2 SD above normal value Plasma procalcitonin .60 s.20 bpm or PaCO2 . the state of intravascular hydration. The concept is not unlike that of Advanced Trauma Life Support (ATLS).90 beats min21) Tachypnoea (.5 mg dl21) Coagulopathy (INR . empyema of the gall bladder.g. it is prudent to examine patients systematically looking for a source of infection (Table 4). burns. and acute pancreatitis. 40 mm Hg from baseline in the absence of other causes for hypotension SIRS Sepsis Severe sepsis Septic shock Sepsis-induced hypotension causes include severe trauma or haemorrhage and acute systemic disease.5 (d) Organ dysfunction parameters: Hypoxic (PaO2 /FIO2 .90 beats min21 o ventilatory frequency .3.368C) Tachycardia (. Infection: documented or suspected infection 2.388C or .0. including myocardial infarction.g.3 kPa o WBC . The examination should focus on the severity of SIRS.90 mm Hg or a reduction of .70% CI. trauma. particularly in agitated un-cooperative patients. hypotension. and bony infections). aPPT. early haemodynamic optimization before the development of organ failure reduced mortality by 23% in comparison with those who were optimized after the development of organ failure.88C) Hypothermia (core temp. . or ICU. The primary source may be self-evident (e. plus hypoperfusion abnormalities A systolic arterial pressure . Table 4 summarizes the presentation of severe sepsis syndrome.

fluid loading has been achieved. and the lack of evidence-based medicine to underpin its guidelines. are crucial and frequently coincide with the time for emergency surgery. and vasopressor medication. Although its detractors point out that bundled therapies are not individualized to a particular patient’s needs. and 28 day outcome.15 – 17 Resuscitation measures begun in the emergency room can be continued even if the patient requires diagnostic imaging studies or admission to the ICU before transfer to the operating theatre.11 18 There is little disagreement among clinicians that in the hypotensive septic patient with lactate . Transfusion of red blood cells may be considered if tissue oxygen delivery remains inadequate.31) in the management of septic shock.11 16 Colloid with pentastarch therapy was associated with higher rates of acute renal failure and renalreplacement therapy than Ringer’s lactate and its toxicity is increased with accumulating doses. given clinical situations.g. The first 6 h of resuscitation of septic patients. and in sufficient dosage to achieve therapeutic concentration. administration of i. and ICU or high dependency unit admission must be considered.19 There is no evidence to support the use of dobutamine to achieve supernormal oxygen delivery in terms of improving outcomes.v. fluids. the so-called ‘golden hours’. serum lactate not decreasing). P¼0.11 However. aiming to reach the following clinical endpoints: CVP 8 –12 mm Hg.v. mixed venous oxygen saturation (SvO2 ). Appropriate samples should be obtained for culture before giving first-line anti-microbial therapy.7 Vasopressor support with norepinephrine may be considered even before optimal i. Low-dose vasopressin (0. central venous oxygen saturation: . further larger clinical studies are required before levosimendan becomes a widely accepted therapy in septic shock. There is no evidence that delaying until the start of the surgical procedure or until microbiology culture results are available is beneficial. Placement of a central venous catheter (CVC) will allow measurement of central venous pressure (CVP). The choice of agents should be based on the clinical history.22 A single randomized controlled trial in 28 patients with septic shock and ejection fraction . duration of renal replacement therapy. volume resuscitation using crystalloids or colloids should be used initially. Supplemental oxygen therapy is valuable in severely septic patients even if they do not have signs of respiratory distress.03 units min21) may be subsequently added to reduce the requirement for high-dose norepinephrine alone.22 23 However.v. and the local pattern of sensitivity to anti-microbial agents. Its inotropic effect is attributable to increased cardiac troponin C sensitivity to calcium.v. there is nonetheless some evidence that the process of care and outcomes improved after educational programmes were instituted based on the Surviving Sepsis Campaign. There is no evidence-based support for one type of i. The systemic and pulmonary vasodilator effect is attributable to its opening of ATP-dependent potassium channels. fluid administration should be stopped when filling pressures are high and no further improvement seen in tissue perfusion is seen (e.48 h after conventional treatment found that cardiac index and renal function indices improved after levosimendan. optimal penetration of anti-microbial drugs into infected tissues. duration of mechanical ventilation.45% persisting . urine output 0.3 mmol litre21. physical examination. Further i. fluid over another with regard to ICU stay.v.14 Anti-microbial drugs are best given i. a study in septic patients showed no difference in efficacy and safety with epinephrine alone compared with norepinephrine plus dobutamine (28 day mortality: 40% vs 34% respectively. if there is evidence of continued low cardiac output despite adequate cardiac filling and fluid resuscitation. If the patient is haemodynamically unstable. invasive arterial pressure monitoring. Broadspectrum agents should be used initially with one or more agents active against all likely bacterial/fungal pathogens.16 – 18 Resuscitation efforts should be continued as long as haemodynamic improvement accompanies each step in the process. central venous access.BJA Table 3 Aetiology of severe sepsis Infective causes CNS infections CVS infections Respiratory infections Renal infections GIT infections Skin and soft tissue infections Bone and joint infections Non-infective causes Severe trauma Haemorrhage Complication of surgery Complicated aortic aneurysm Myocardial infarction Pulmonary embolism Cardiac tamponade Subarachnoid haemorrhage Burns Acute pancreatitis Drug overdose/toxicity Diabetic ketoacidosis Adrenal insufficiency Anaphylaxis Eissa et al.11 – 13 Antibiotic therapy It is imperative that i. antibiotics should be started as early as possible after the diagnosis of severe sepsis and septic shock.5 ml kg21 h21. likely pathogen(s).v. The Surviving Sepsis Campaign recommends that dobutamine is the first-line inotrope therapy to be added to vasopressors in septic patients.70% (Table 5). Immediate tracheal intubation and mechanical 736 . compared with dobutamine.20 21 Levosimendan may be a useful adjunct to conventional inotropic therapy in cases of refractory myocardial dysfunction in sepsis. Haemodynamic resuscitation The objective of preoperative resuscitation measures is to rapidly restore adequate oxygen delivery to peripheral tissues.10 18 19 Inotropes are added to volume resuscitation and vasopressors. mean arterial pressure 65 mm Hg.

liver failure.v. Streptococcus bovis. purulance (a) Increase in capillary permeability. Neiserria meningitides. The non-infective causes 737 . orthopnoea. coagulase-negative staphylococci.. impaired myocardial contractility.Anaesthetic management of patients with severe sepsis BJA Mechanism Alteration in: blood –brain barrier neurotransmitter levels. dysuria. i. tenderness. cholestasis (a) Frequency. for example. abdominal pain. impaired responsiveness to vasopressor agents. alveolar flooding (b) Neutrophils recruited to the lung (c) Pulmonary microemboli platelet aggregates Gastrointestinal system GU system Vomiting. Coxiella burnetii. ventilation of the lungs can be considered if the patient’s level of consciousness is low or if there is progressive distress and hypoxia. receptor function energy availability Common system pathogens Community-acquired pathogens: Streptococcus pneumoniae. drowsiness. Computerized tomography is the most useful imaging modality for complex soft-tissue infections and deep-seated infections in the abdomen and thorax. pathophysiology. methicillin-resistant coagulase negative Staphylococcus (c) Myocardial depression (d) Down-regulation of adrenergic receptors heart valve dysfunction Respiratory system Hypoxaemia. tachycardia. coli. methicillin-resistant S.. E. Legionella sp. methicillin-resistant Staphylococcus epidermidis. short of breath. fungus (b) Increase in microvascular permeability and hypoalbuminaemia Major nosocomial pathogens: Staphylococcus spp. irritability coma headache. Listeria monocytogenes Nosocomial pathogens: Pseudomonas aeruginosa. it is important to consider the presence of an alternative diagnosis. antimicrobial therapy. diarrhoea.5 ml kg21 h21 ≥30% of SIRS or an iatrogenic complication. increased cardiac output.g. inadequate replacement. it is important that all other therapeutic measures (e. Ultrasound imaging of the biliary and urinary tract may also be considered.24 If there is an inadequate response to these resuscitation measures. photophobia Cardiovascular system Hypovolaemia. Streptococcus spp. neck stiffness. Bacteroides fragilis Major nosocomial pathogens: aerobic Gram-negative bacilli anaerobes Mechanisms? Major community-acquired pathogens: any of the above-mentioned organisms as a result of bacteraemia Major nosocomial pathogens: any of the above-mentioned organisms as a result of bacteraemia Major community-acquired pathogens: S. Staphylococcus aureus. mechanical ventilation) are continued in a comprehensive manner. change in sputum: volume. tachypnoea. decreased systemic vascular resistance (SVR). haematuria. excessive insensible losses Major community-acquired pathogens: Enterococcus. flank pain. Escherichia coli Table 4 Common presentation. cyanosis. Major nosocomial pathogens: aerobic Gram-negative bacilli Table 5 Goal-directed therapy: a summary of clinical targets Clinical parameter Central venous pressure Mean arterial pressure Central venous oxygen saturation Urine output Haematocrit Goal 8 – 12 mm Hg (≥8 mm Hg in spontaneously breathing patient. raised venous pressure (a) Poor intake. If diagnostic imaging studies are considered appropriate. aureus. Expert interpretation of all imaging studies should be sought to assist in planning the optimal management strategy. and pathogens in severe sepsis System affected Central nervous system Signs and symptoms Confusion. ≥12 mm Hg in ventilated patients) Between 65 and 90 mm Hg ≥70 mm Hg ≥0. use of accessory muscles. Diagnostic imaging Diagnostic imaging studies are increasingly important in confirming the site of infection. coli. pneumoniae. Campylobacter. Haemophilus influenzae. tension pneumothorax after CVC placement. renal failure Major community-acquired pathogens: E. should also be considered (Table 3). fluid resuscitation. excluding alternative pathology and guiding radiological or surgical source control procedures.

or inadvertent organ injury. which is associated with improved outcome.v. microbiologist-infectious disease physician. Options for the use of vasopressors include ephedrine. infective endocarditis with structural heart damage leading to cardiogenic shock) which may require urgent surgical intervention. upper airway infections leading to airway compromise. Before induction Many source control procedures are done out of hours. Eissa et al. intravascular volume loss. where percutaneous drainage and full supportive therapy facilitate delayed surgical intervention. and its effects on myocardial contractility are minimal. Debridement refers to the physical removal of non-viable solid tissue usually by an open surgical approach. and metaraminol. Although it can cause bradycardia. fistulas. If large volume loss is anticipated during the surgical procedure. and timing of the next scheduled dose is important to optimize type and timing of intraoperative 738 . bleeding. a modified rapid sequence induction. and radiologist is essential for rapid implementation of an effective treatment plan. Options for the induction technique are many. Invasive haemodynamic monitoring is likely to be indicated in addition to standard intraoperative monitoring. immediate surgery or within 1– 2 h of presentation (e.v. etomidate. and surgical stress.25 The immediate goal is to achieve adequate control of the source of infection with the least physiological embarrassment. phenylephrine. opioids may be increased by impaired hepatic and renal perfusion. it is worth considering placement of an appropriate volume resuscitation intravascular device. Source control intervention may cause further complications such as bleeding. may be considered before induction of anaesthesia.29 Placement of a cuffed tracheal tube is facilitated by the use of neuromuscular blocking agents (preferably non-histamine releasing agents). Drainage procedures apply to wellcircumscribed infections that can be drained either percutaneously under image-guidance or by an open surgical approach. anaesthesia. unstable patient.v. has much to recommend it in the setting of induction of anaesthesia in the septic. either as a primary agent or as a background adjunct to another induction drug. The exception to this rule is peripancreatic necrosis associated with acute pancreatitis. Awareness of the microbiological samples sent for culture. Remifentanil infusion. Definitive surgical interventions are indicated to correct anatomical abnormalities and prevent further contamination. the anti-microbial agents which were started.g. the effects and duration of action of i.10 18 The goal of mechanically Intraoperative management The primary goal of the anaesthetist during the intraoperative period is to provide safe and optimal care for critically ill septic patients so that they may benefit maximally from the surgical or radiological source control procedure. anaesthetic agents. Induction of anaesthesia and initiation of mechanical ventilation Patients undergoing source control procedures are in an inherently unstable cardiovascular state due to the combined effects of sepsis. Further. surgeon. Some thought should be given early to whether the patient may require ICU management after operation. so it is important that the anaesthetist has appropriate help available in the operating theatre. using small doses of i. remifentanil avoids sudden reductions in systemic vascular resistance. Most i. including ketamine. perhaps using rocuronium rather than succinylcholine to facilitate tracheal intubation.28 Therapeutic concentrations of effective antimicrobial agents should be maintained throughout the perioperative period as the procedure itself may cause further bacteraemia and clinical deterioration. Norepinephrine infusion may be used for a more prolonged effect. Because many surgical procedures on severely septic patients occur on an emergency basis. The optimal timing of any surgical intervention depends on the diagnosis and the clinical course of the patient. The choice of induction agent or narcotic is less important than the care with which they are administered. Continued volume resuscitation and incremental doses of vasopressors are helpful to counteract the hypotensive effect of anaesthetic agents and positive pressure mechanical ventilation.25 26 There are also a number of commonly occurring severe infections (intra-abdominal abscess. A surgeon with experience in dealing with complex infections in critically ill patients is best placed to be involved in the decision-making process regarding a particular source control procedure. or inhalation anaesthetic agents cause vasodilation or impaired ventricular contractility. Induction of anaesthesia is ideally a deliberate step-wise process. but there is no evidence base to support the use of any of these in preference to another. With the exception of remifentanil. In some patients. De-nitrogenation of the lungs. many of these patients are tachycardic.27 Clear and timely communication between the anaesthetist. antimicrobial therapy. Serial measurements of arterial blood gases and lactate concentration should be readily available from near-patient testing equipment. which can be discussed with the patient and their family. infections associated with intravascular or prosthetic device. The majority of surgical source control procedures are optimally carried out in the operating theatre under general anaesthesia.BJA Source control Source control measures include drainage or debridement procedures and definitive correction of anatomical abnormalities leading to ongoing contamination of previously sterile tissue. breathing 100% O2 through a tightly fitted facemask for up to 3 min. and slow administration of more commonly used agents such as propofol. may be required. necrotizing fasciitis) is lifesaving. Ketamine or midazolam may provide a degree of haemodynamic stability and shortacting opioids such as fentanyl or alfentanil will enable a reduction in the dose of anaesthetic induction agent. titrated to clinical response. It is vital that the anaesthetist assumes a central role in the multidisciplinary team.

The difference between the pressure inside and outside the alveolar air space at end-inspiration is the transpulmonary pressure. In all other circumstances. a reduction in transpulmonary pressure).30 35 36 Recruitment of collapsed alveoli by manually ventilating the patient to a peak airway pressure of 30–40 mm Hg for short periods may reduce shunt and improve intraoperative oxygenation. During the surgical procedure. Therefore. Hypercarbia should be avoided specifically in patients with raised intracranial pressure. oesophageal Doppler. The inspired oxygen concentration can be increased until SaO2 is at least 90% and the use of PEEP may be considered during the surgical procedure. coagulation screen. and their own experience and expertise. Extra-alveolar or pleural pressure can be abruptly increased by placing the patient in the Trendelenberg position or by the increased intra-abdominal pressure associated with inflation of a pneumoperitoneum for laparoscopic surgery. intraoperative CVP values may be increased by raised intra-thoracic and intra-abdominal pressure. Throughout the surgical procedure. The anaesthetist should choose the technique which they believe best fits with their assessment of the individual patient’s risk factors and co-morbidities. Although a CVP of 8–12 cm H2O is a commonly used haemodynamic goal in the initial resuscitation of septic patients. lactate. such as patients with emphysematous bullae or severe chronic obstructive pulmonary disease. where oxygenation is adequate. and glucose concentration is advisable.32 In patients with significant lung dysfunction. agents. Changes in dynamic markers of volume responsiveness can be used intraoperatively to guide i. During surgery. full blood count.33 34 There are many devices available to monitor changes in cardiac output either continuously (pulmonary artery catheter.v.5 mg kg21 min21. measured during volume-control mechanical ventilation when an end-inspiratory pause has been applied. . which is caused by the increased capillary permeability in sepsis. Plateau airway pressure. Every ventilating patients with severe sepsis is to use sufficiently high fractional inspired oxygen concentration (F IO2 ) to maintain adequate oxygenation (PaO2 . or the later stages of pregnancy. Transfusion of blood products should proceed without delay if the surgical procedure is complicated by excessive blood loss.31 35 Protective lung strategies are advisable for mechanical ventilation of the lungs. and opioids. route.g. which is tolerated and appears relatively safe in the short term (i. The adequacy of global oxygen delivery may be assessed by serum lactate . where low alveolar minute ventilation to minimize ventilatory lung damage inevitably results in a degree of hypercapnia (typically PaCO2 . Whatever technique is used. the depth of anaesthesia achieved can be estimated using bispectral index monitoring. high transpulmonary pressures are associated with lung injury.12 kPa).30 Shear forces caused by high tidal volumes or high inspiratory pressures will exacerbate lung injury. Concurrent transoesophageal echocardiography or oesophageal Doppler may be used to define changes in stroke volume variation.25 –0. especially in patients with regular sinus heart rhythm and whose lungs are ventilated by controlled mechanical ventilation. hypercarbia may be well tolerated and there is some evidence that permissive hypercapnia may have inherent protective effects. There is now strong evidence supporting a low tidal volume ventilatory strategy.g. to minimize the impact of positive pressure ventilation on the lung tissue itself. Changes in dynamic markers (pulse pressure variation. compensated metabolic acidosis. maintenance of stable concentrations of anaesthetic agents in the brain may be more reliably achieved when using i. and excessive transpulmonary pressures (e. i. the haemodynamic state may be further complicated by blood loss or systemic release of bacteria or endotoxins.v. or serial measurement of 739 . volume therapy. the concept of ‘permissive hypercapnia’ has arisen. rather than inhalation agents. cardiac filling pressures. systemic arterial pressure) can be adjusted to optimize tissue oxygen delivery rather than to achieve set values of cardiac output or arterial pressure.25–30 cm H2O.v. Options for maintaining anaesthesia include inhalation agents. The pressure outside the alveolar sac cannot be measured directly but is estimated clinically by assessing changes in pleural pressure.v.8–9 kPa). and the associated risk of barotraumas). cardiovascular parameters (heart rate.70%. . Pulmonary gas exchange may deteriorate if pleural pressure is increased and plateau pressure remains constant (i. In patients with early acute lung injury.31 Maintenance of anaesthesia There is no evidence to suggest an outcome benefit when anaesthesia is maintained by the inhalation or i.Anaesthetic management of patients with severe sepsis BJA mixed-venous O2 saturation). impedance plethysmography) or at discrete time intervals (trans-thoracic or transoesophageal echocardiography. more than 3–4 days). Management options for hypoxaemia during maintenance of anaesthesia include increasing the inspired oxygen concentration and incrementally increasing PEEP.e.20–25 cm H2O. stroke volume variation) have been shown to predict volume responsiveness more accurately than pressure-based estimates (CVP or pulmonary artery occlusion pressure). On the other hand.e. The PEEP may be cautiously increased in haemodynamically stable patients if there is still hypoxia despite increasing the FIO2 .2 mmol litre21 and mixedvenous O2 saturation . Caution is advisable in undertaking this manoeuvre in patients at risk of pneumothorax. inotropic state. The MAC of inhalation anaesthetic agents is reduced in severe sepsis. electrolytes. is an indicator of the maximal pressure applied inside the alveolar sac. and also on venous return and cardiac output. the ventilatory strategy should aim to strike an expedient balance between significant reduction in transpulmonary airway pressure (e. for example. regular near-patient testing of arterial blood gases. with associated reduction in alveolar ventilation). remifentanil infusion using 0. Intravascular volume resuscitation should continue as indicated throughout the surgical procedure. Oxygenation may be impaired by non-cardiogenic pulmonary oedema.

BJA effort should be implemented to avoid intraoperative hypothermia as it is associated with impaired platelet and coagulation factor dysfunction. Postoperative management of patients with severe sepsis It is important to note that pre-resuscitation measurements should be used to calculate the Intensive Care admission APACHE score and not those that have improved after resuscitation and the surgical procedure. which was started before operation. or if between 5000 and 30 000 mm23 with significant bleeding risk.40 48 Therefore. administration of further neuromuscular blocking agents to facilitate surgical closure of the abdomen or thorax may be considered. Low tidal volumes (up to 6 ml kg21 of the predicted body weight) and permissive hypercapnia may be considered. while avoiding the systemic effects of opioid and may be used if an individual assessment of the risk– benefit balance suggests that it may be justified in their particular circumstances. mechanical ventilation settings can be decided.37 Eissa et al.41 The use of high PEEP (10 – 15 cm H2O) may be limited by the degree of associated haemodynamic instability. The rate of blood loss should be minimal before leaving the operating theatre. Having secured the patient’s airway. antimicrobial agents used. Antimicrobial regimens can be reassessed daily in light of microbiological results. The F IO2 can be decreased (i. Neuraxial block (spinal and epidural anaesthesia) should be undertaken with caution. prevent resistance. sedation. However.7 g dl21) had a significantly lower mortality rate (22% vs 28%) than those who were transfused at higher Hb levels. with the objective of minimizing ventilation-induced volutrauma and barotraumas to the lungs. Supplemental doses of antimicrobial agents may be considered. and mechanical ventilation are maintained at the conclusion of the surgery.14 28 It has been shown that patients who had a restrictive red blood cell transfusion strategy (transfusion avoided unless Hb . severely septic patients may be at increased risk of this and other serious complications. Although there is no evidence that placement of an epidural catheter in severely septic patients increases the risk of epidural abscess or haematoma formation. the achieved transpulmonary pressure (plateau pressure – pleural pressure) should be limited to 25 – 30 cm H2O to minimize lung parenchymal ventilatory damage. 22 made a complete recovery from their serious complication within the follow-up period. provided that arterial pH does not decrease below 7. In Role of regional anaesthesia and nerve blocks in anaesthesia for septic patients Peripheral nerve block may be effective at minimizing the sympathetic response to a painful stimulus.43 44 Continuation of adequate glycaemic control (. response to resuscitation measures.35 36 41 It is obviously important that antimicrobial therapy. details of the surgical procedure preformed. End of surgical procedure At the conclusion of the surgical procedure. .8 (95% CI 1.20 Platelets are transfused if counts are ≤5000 mm23 regardless of bleeding. local or systemic spread of infection. analgesia.38 39 Recent blood tests confirming normal coagulation are essential. The incidence of permanent injury from CNB was 4.20.9–6.60%) to achieve an SpO2 of 93 – 95%. should be continued in the ICU and the time of the next scheduled dose was noted. This is most likely to be achieved using low-pressure settings. while epidural anaesthesia appears to have a very low risk of permanent neurological sequelae overall. and suitably set alarm limits. and adjusted to ensure efficacy.5 mmol litre21) is important in the control of the septic process.1) per 100 000 cases. Recombinant human activated protein C (rhAPC) may be considered in adult patients with sepsis-induced organ dysfunction with clinical assessment of high risk of death (typically APACHE score . Of the 52 cases which were the focus of follow-up for permanent injury from CNB. with the possible exception of patients with acute myocardial infarction and unstable angina. Duration of therapy should be limited to 7–10 days. 740 . Safe transfer of the patient to the ICU is essential. When an endinspiratory pause is included in the respiratory cycle in the volume-control mode. a high fractional inspired oxygen concentration (F IO2 ).2 (95% CI 2.1) per 100 000 and that of paraplegia or death was 1.25 or multiple organ failure) if there are no contraindications to rhAPC. A focused hand-over report is helpful for the ICU colleagues which highlights the clinical presentation.e. Ongoing infusions of vasopressor medication should be adjusted to match the present intravascular volume and the new mechanical ventilator settings. the presence of coagulopathy. APACHE II .20 or one organ failure) should not receive rhAPC. blood products used intraoperatively.36 Pressure-controlled or volume-control mode of mechanical ventilation can be used. since the haemodynamic effects of these techniques in the setting of sepsis-induced cardiovascular compromise may be difficult to reverse. a substantial proportion of clinical opinion would seem to believe that the risks associated with using it in the context of severe sepsis is not justifiable. and the fact that local anaesthetics may not work properly in the presence of infection or acidosis may limit the application of regional techniques in septic patients. Adult patients with severe sepsis and low risk of death (typically. More than 700 000 central neuraxial blocks are conducted annually in the UK. and to avoid toxicity.0 –3.42 Fresh-frozen plasma may be used to correct laboratory clotting abnormalities only if there is clinical bleeding or an invasive procedure is planned.20 Deep venous thrombosis thromboprophylaxis should usually be considered when concerns about coagulopathy have abated.8. In patients who will require further surgery and in all severely ill patients. and any specific problems that should be anticipated in the postoperative period.

Enteral nutrition via a nasogastric tube is the best choice to maintain enterocyte integrity and nourish the patient. is based on judicious use of fluids. Patients with severe sepsis syndrome often require surgery for source of infection control. Early i. and inotropes. Although this study was conducted in the ICU setting. Preoperative resuscitation. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the ICU.03).g. use of levosimendan for intraoperative inotropic support.2 mmol litre21) was higher in the intensive-therapy group than in the conventional-therapy group (17% vs 4%. respectively. P.30 In this study.B. Conflict of interest D.89. e. 95% CI 0.0. A 7 day trial treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events (P. P¼0.V. and electrolyte levels. severe sepsis is a major healthcare issue. Maintenance of anaesthesia is challenging. it seems prudent to extrapolate the finding to appropriately selected patients in the perioperative period.001] than did conventional intermittent haemodialysis on alternate days. in severely septic patients. aimed at optimizing major organ perfusion.’s time was supported by The Sisk Foundation. the observed mortality being 67% for intermittent haemodialysis vs 65% for continuous haemodiafiltration.J. fewer hypotensive episodes during haemodialysis. Continuous veno-venous haemodiafiltration does not confer any survival benefit when compared with intermittent haemodialysis. respectively. Finally where applicable. In a multicentre. continuous renal replacement may be more practical in hemodynamic unstable patients.46 However. it is wise to raise the subject of advanced care planning with the patient and his family. administration of effective antimicrobial therapy is essential. Analgesia and sedative medication is continued by infusion. randomized trial of ICU patients.14). 95% CI 0.44 I.54. However.0.001). requiring achievement of optimal volume status. P¼0.10 There appears to be a benefit to the use of low-dose glucocorticoids (e. but excessive use of sedation or neuromuscular blocking agents is not recommended. Therefore. 9 (2) vs 16 (6) days. randomized.28– 0. vasopressors. Patients may become rapidly hypoglycaemic if TPN or enteral nutrition is stopped during the perioperative period. adjusted odds ratio (OR) 0.10 45 Whether administration of low-dose steroids during intraoperative management of the septic patient would improve haemodynamic stability or outcome is unknown and seems unlikely.J. four times daily. Gastrointestinal protective measures (stress ulcer prophylaxis) and antiemetic drugs are also prescribed. P¼0. these results may not apply specifically to patients with severe sepsis. and ongoing monitoring of arterial blood gases. in septic patients who did not receive corticosteroids. P¼0. blinded. and more rapid resolution of acute renal failure [mean (SD).05).7. using lowest effective doses of a range of agents. Total parenteral nutrition (TPN) should be considered if there is a surgical contraindication to enteral nutrition or if nutritional requirements are not fully met by enteral nutrition alone. there was no significant difference between strict glycaemic control (blood glucose 4–6 mmol litre21) and more liberal glycaemic control (blood glucose 6–10 mmol litre21) in the rate of death or the mean organ failure score.B.v.1. The role of glucocorticoids in the management of patients with severe sepsis requires further investigation. Sodium bicarbonate is not recommended for correcting acidosis unless pH . and realistic expectations and outcomes targeted. where normovolaemic septic patients seem refractory to vasopressor therapy to maintain major organ perfusion and haemodynamic stability).05). international. P¼0. Funding D. controlled trial of patients with septic shock who were treated with corticosteroids. with an RR of 1. vasopressin use was associated with increased mortality compared with norepinephrine (34% vs 21%. In conclusion.50. The care of critically ill septic patients requiring anaesthesia and surgery will be further enhanced by testing promising therapeutic strategies.02]. a large. hydrocortisone may be considered when hypotension responds poorly to fluid resuscitation and vasopressors. In contrast. hydrocortisone 50 mg.68– 1. there were 81 deaths (70%) in the placebo group and 66 deaths (58%) in the corticosteroid group at the end of ICU stay [relative risk (RR) 0. in well-designed clinical trials.7 Nutrition is one of the cornerstones of management in critically ill septic patients. is a member of the Editorial Board of BJA. the rate of severe hypoglycaemia (glucose level ≤2.01). there was significantly decreased mortality in patients who received vasopressin compared with norepinephrine (36% vs 45%. as was the rate of serious adverse events (11% vs 5%. 741 .00.g.45 Hydrocortisone in a dose of 200 mg per day in four divided doses or as a continuous infusion in a dose of 240 mg per day (10 mg h21) for 7 days is recommended for septic shock in the ICU setting. Renal replacement therapy may be initiated to correct acidosis.82.Anaesthetic management of patients with severe sepsis BJA Acute renal failure occurs in 23% of patients with severe sepsis. or fluid overload and may be continued until acute tubular necrosis has recovered. Intraoperative management requires careful induction of anaesthesia.94– 1.03 (95% CI 0.47 Although the weight of current evidence suggests that higher doses of renal replacement may be associated with improved outcomes. A study comparing daily with alternate-day haemodialysis found that daily haemodialysis resulted in better control of uraemia. avoidance of lung injury during mechanical ventilation. The anaesthetist has a crucially important role in coordinating and delivering resuscitation and therapeutic strategies to optimize patient survival outcome. with a persistently high mortality. hyperkalaemia. blood glucose should be maintained in the range 6–10 mmol litre21. haematological and renal indices. P¼0.

Influence of sepsis on sevoflurane minimum alveolar concentration in a porcine model. 2001 SCCM/ESICM/ACCP/ATS/ SIS International Sepsis Definitions Conference. 173: 71– 5 28 Kumar A. N Engl J Med 2000. 101: 1644– 55 4 Levy MM. Permissive hypercapnia—role in protective lung ventilatory strategies. corticosteroid treatment. 28: 2729– 32 19 Djillali A. Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis. 31: 1250– 6 5 Martin GS. 25: 753– 68. Crit Care Med 2000. Tavernier B. 370: 676–84 20 American Society of Anaesthesiologists: Task Force on Blood Component Therapy: practice guidelines for blood component therapy. French ICU Group for Severe Sepsis. SCCM/ESICM/ ACCP/ATS/SIS. et al. 1996 to 2004: secondary analysis of a high quality clinical database. et al. Tournadre JP. Marshall JC. J Am Med Assoc 2008. Balk RA. Erratum in: Crit Care Med 2008. Nouette-Gaulain K. N Engl J Med 2004. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Brazzi L. 101: 761– 8 34 Derichard A. 86: 832– 6 33 Biais M. Intensive Care Med 2004. Bloos F. N Engl J Med 2003. 253: 1160– 5 27 Mier J. Maki DG. 4: 519–27 Eissa et al. Dieter Ayers for the Vasopressin and Septic Shock Trial Investigators. De Michele M. risk factors. Chest 1998. for the CATS Study Group. De CS. Intensive Care Med 2005. Revel P. Crit Care Med 2003. Welch CA. The SAFE study: a comparison of albumin and saline for fluid resuscitation in the intensive care unit. Sunderram J. Society of Critical Care Medicine. Pelosi P. Anesthesiology 1996. Artigas A. et al. Interaction of vasopressin infusion. 5: 362–7 22 Hunter JD. Paz HL. Early versus late necrosectomy in severe necrotizing pancreatitis. Martin AA. Carlet JM. Sztark F. Surviving Sepsis Campaign. Effects of perfusion pressure on tissue perfusion in septic shock. 114: 541–8 30 The Acute Respiratory Distress Syndrome Network: ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. Crit Care Med 2010. Levy MM. Gordon AC. American College of Chest Physicians/Society of Critical Care Medicine. Crit Care Med 2002. Castillo A. Doyon F. 358: 125– 39 8 Levi M. Robledo F. Incidence. Townsend SR. Boyce N. 345: 1368–77 18 LeDoux D. Engel C. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomized trial. 38: 683–4 14 Handelsman J. Teboul JL. O’Croinin D. 30: 347–56 32 Allaouchiche B. The ACCP/SCCM Consensus Conference Committee. viii 29 Kollef MH. N Engl J Med 2001. 10: R42 3 Bone RC. American College of Emergency Physicians. 299: 2294– 303 13 Levy MM. Ahrens TS. The epidemiology of sepsis in the United States from 1979 through 2000. Astiz ME. Parrillo JE. 348: 1546– 54 6 Brun-Buisson C. 35: 1414– 5 2 Harrison DA. et al. International Sepsis Forum. Japanese Society of Intensive Care Medicine. et al. Debon R. Kavanagh BP. Canadian Critical Care Society. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. viii–ix 26 Natanson C. American College of Chest Physicians. McLoughlin P. Levy MM. Crit Care Med 2010. Br J Anaesth 2008. Doddi M. Wales and Northern Ireland. Cottenceau V. American Association of Critical-Care Nurses. The use of continuous IV sedation is associated with prolongation of mechanical ventilation. Shoemaker WC. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. 350: 2247– 56 16 Gattinoni L. International Surviving Sepsis Campaign Guidelines Committee. N Engl J Med 1995. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Levy NT. N Engl J Med 1994. et al. Bellomo R. et al. Cerra FB. 176: 761–7 742 . Moss M. Surgical Infection Society. 333: 1025– 32 17 Rivers E. Renault A. Edusepsis Study Group. ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure. Crit Care Clin 2009. Sepsis and the heart. Carpati CM. et al. Crit Care Med 2008. DeMarco FVC. Yau EHS. Uncalibrated pulse contour-derived stroke volume variation predicts fluid responsiveness in mechanically ventilated patients undergoing liver transplantation. Am J Surg 1997. 36: 1394– 6 12 Ferrer R. Early goal-directed therapy in the treatment of severe sepsis and septic shock. Chassard D. 36: 296– 327. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. Br J Anaesth 2009. World Federation of Societies of Intensive and Critical Care Medicine. et al. Mannino DM. Leon EL. Crit Care 2001. Shelhamer JH.BJA References 1 Dombrovskiy VY. Inflammation and coagulation. 104: 3–11 23 Morelli A. et al. Nguyen B. J Am Med Assoc 1995. European Society of Clinical Microbiology and Infectious Diseases. Meta-analysis of hemodynamic optimization in high-risk patients. N Engl J Med 2008. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Elevation of systemic oxygen delivery in the treatment of critically ill patients. Carlet J. Havstad S. Dellinger RP. Japanese Association for Acute Medicine. Optimizing antimicrobial therapy in sepsis and septic shock. Chest 1992. et al. 342: 1301–8 31 Laffey JG. Crit Care Clin 2009. 15 Finfer S. German Competence Network Sepsis (SepNet). 30: 1686– 92 10 Russell JA. 38(2 Suppl): S26– 34 9 Kern JW. A multicenter prospective study in intensive care units. Crit Care Med 2007. et al. Crit Care 2006. Principles of source control in the management of sepsis. Walley KR. 37: 811–8 11 Dellinger RP. Automated pulse pressure and stroke volume variations from radial artery: evaluation during major abdominal surgery. et al. Timmins AC. et al. Akamine N. and outcome of severe sepsis and septic shock in adults. 25: 733–51. 274: 968–74 7 Brunkhorst FM. Robin E. Fink MP. and mortality of septic shock. European Society of Intensive Care Medicine. Duflo F. A trial of goal-oriented hemodynamic therapy in critically ill patients. Al Naqbi A. The epidemiology of severe sepsis in England. et al. Early Goal-Directed Therapy Collaborative Group. 31: 638– 44 24 Hayes MA. Red blood cell transfusion does not increase oxygen consumption in critically ill septic patients. et al. Society of Hospital Medicine. Stripoli T. Effects of levosimendan on systemic and regional haemodynamics in septic myocardial depression. Br J Anaesth 2010. Crit Care Med 2009. et al. the ICNARC Case Mix Programme Database. 84: 732– 47 21 Fernandes CJ. et al. Vigno P. Eaton S. van der Poll T. J Am Med Assoc 1985. Am J Respir Crit Care Med 2007. Blanco R. Lancet Infect Dis 2004. Br J Anaesth 2001. Eddleston JM. European Respiratory Society. 103: 678– 84 35 Grasso S. et al. Intubation of the trachea in the critical care setting. Lancet 2007. 330: 1717– 22 25 Marshall JC.

random42 He ized. Crit Care Med 2004. Acta Anaesthesiol Scand 2008. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Levy H. Pottinger JM. et al. Central neuraxial block: defining risk more clearly. 102: 179–90 36 Hager DN. 346: 305–10 47 Tonelli M. Counsell D. Royal College of Anaesthetists Third National Audit Project. 23: 448–9 743 . et al. Blajchman MA. Wildsmith JA. Major complications of central neuraxial block: report on the Third National Audit Project of the Royal College of Anaesthetists. Sebille V. 172: 1241–5 37 Insler SR. et al. Comparison of early enteral feeding versus parenteral nutrition after resection of esophageal cancer. Lang SM. N Engl J Med 1999. Krishnan JA. 33: 21 –30 ´bert PC. 20: 335–40 39 Schuz-Stubner S. Manns B. Perioperative thermoregulation and temperature monitoring. Feller-Kopman D. 102: 151–3 41 Ferguson ND. and mortality in patients with acute respiratory distress syndrome. Daily hemodialysis and the outcome of acute renal failure. Coffin SA. 24: 823– 37 38 Guay J. 40: 875–85 48 Cook TM. Benefits of adding epidural analgesia to general anesthesia: a meta-analysis. Charpentier C. Airway pressures. J Am Med Assoc 2002. Wells G. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. Clermont G. tidal volumes. Br J Anaesth 2006. Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial. controlled clinical trial of transfusion requirements in critical care. J Crit Care 2008. Frutos-Vivar F. et al. Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery. 52: 1144–57 40 Buggy DJ. Br J Anaesth 2009. Herwaldt LA. Esteban A. 288: 862– 71 46 Schiffl H. Hayden DL. Sessler DI. 340: 409–17 43 Farimani MR. Am J Respir Crit Care Med 2005. Nosocomial infections and infection control in regional anaesthesia. Fischer R. et al. Am J Kidney Dis 2002. Br J Anaesth 2009.Anaesthetic management of patients with severe sepsis BJA 44 Laterre PF. Crit Care Med 2005. Bajestani NN. A multicenter. et al. Anesthesiol Clin 2006. 32: 2207–18 45 Annane D. N Engl J Med 2002.

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