Acute Resuscitation and Crisis Management: Acute Critical Events Simulation (ACES)

Chapter 20 Sepsis: New and Emerging Therapies

C H A P T E R 2 0 SEPSIS: NEW AND EMERGING THERAPIES RICHARD HODDER A 58-year-old male hospital worker, Mr. Schoque, complains ofbreathlessness and coughfor three days. The presumed diagnosis is a community-acquired pneumonia. His past medical history consisted of hypertension and intermittent atrial fibrillation, for which he was taking coumadin, verapamil and propafenone. There was no known coronary artery disease nor diabetes mellitus. He had quit a 35-pack per year smoking history eight years ago and there was no recent travel nor obvious recent exposure to patients with cough and phlegm. He had been his usual self until three days ago when he developed mild flu-like symptoms. Despite ibuprofen he got worse and one day ago, began to experience chills, fever, right-sided pleuritic chest discomfort and cough productive of purulent phlegm. He started treating himself with some azithromycin left overfrom a previous prescriptionfor his wife, but the next day hefelt significantly worse with persisting cough and fever, increasing chest pain, profound fatigue and progressive shortness of breath. He went to awalk-in clinic, but becausehe looked so ill, he was sent to the local emergency department where he was seenpromptly and noted to bealternately agitated and drowsy. Presently he is breathing at 42 bpm, has aheart rate of 120-140 (ECG; atrial fibrillation with no obvious ischemic changes) and blood pressure 100/40 mm Hg and is febrile at 39.TC. Initial labs: WBC 23,3 x!09 /L (19.8 neutrophils, 2.8 bands, toxic changes); Hgb 105 g/L; platelets 237 x 1QPIL; INK 3.2; CK 89 U/L; urea93 mmol/L; creatinine US^mollL; pH 7,36, Pco2 32 mm Hg; Po2 55 mm Hg and Sao2 89% on an Fio2 -OAOby mask. A chest radiograph confirmed right-sided pneumonia and pleural effusion (Figure 20.1), What is wrong with Mr. Schoque? What areyour immediate management goalsfor Mr. Schoque? Sepsis is a syndrome of systemic inflammatory response related to infection. Sepsis is unfortunately 207 a common, often fatal disorder whose incidence is increasing. The mortality rate associated with severe sepsis is around 50%in most studies.1 The estimated costs related to sepsis are staggering. Fortunately, new strategies and therapeutic options will hopefully improve the management of these challenging patients. The goal of this chapter is to review sepsis and the pathophysiology underlying it. A critical appraisal of the different strategies for sepsis is presented along with an introduction to emerging therapies. Despite advances in our knowledge of disease states and despite technical and pharmacological advances in intensive care, the mortality rate from severe sepsis and septic shock remains unacceptably high in most centres (Figure 20.2).1 '2 In part this reflects our current inability to effectively monitor and modulate dysfunction of the microvasculature, which is the real battleground for sepsis,3 '8 and in part it reflects a certain persisting inability to recognize sepsis in its early stages, in order that definitive and preventive therapies could be started in a more timely fashion than is usually the case. Recently, an international consensus statement on evidence-based management of severe sepsis, the Surviving Sepsis Campaign, has been published9 and its recommendations will be listed throughout this chapter. • Sepsis Nosology In 1992, in an attempt to standardize sepsis research and to address the problem of delayed recognition of sepsis-induced systemic inflammation, the concept of systemic inflammatory response syndrome (SIRS) was put forward.10 '11 In general terms, SIRS was defined as the presence of two or more of the following features of systemic inflammation: fever or hypothermia, leukocytosis or leukopenia, tachycardia,and tachypnea or a supranormal minute ventilation (Figure 20.3). According to this scheme, sepsis is considered to exist when there is SIRS plus a documented infection;severe sepsis indicates sepsis plus documented organ failure (see Table 20.1 for Figure 20.1- Chest X-ray ofCase Presentation Chest radiographof 58-year-oldman with community-acquired pneumoniaand sepsis. Figure 20.2- Changing Mortality from Sepsis Graph demonstrating how mortality rates secondary to sepsis have changedover the last 50years. source: Adapted from Friedman et al.1 definitions of orgcin failure);12 and septic shock indicates severe sepsis plus hypotension (or an elevatedlactate in the absence of hypotension). 208 ACUTE CRITICAL EVENTS SIMULATION (ACES) COURSE SYLLABUS • Epidemiology ofSepsis and Septic Shock Figure 20.3 - Definitions of SIRS, Sepsis Diagram illustrating the definitions of the different...