A 60-year-old woman with stage IV cervical carcinoma undergoes extensive pelvic surgery (pelvic exenteration) in order to remove the tumor. The surgical procedure involves removal of all pelvic organs, removal of a segment of the ileum to construct a new bladder, and a colostomy. At first, the patient appears to be recovering very nicely. During the evening of the third postoperative day, however, the nurse on the night shift notes that the patient's respiratory rate, which was 16-18 per min, has increased to 26 per min. The patient claims that she doesn't feel overly sick. She is not short of breath or in pain, and her temperature is actually slightly subnormal (36.2ºC). By the next morning, she has slight fever (38.3ºC), but she continues to feel reasonably good. Her surgical wound shows no signs of infection, and her abdomen is no more tender than expected. Later in the day, however, it becomes quite clear that the patient is in serious trouble. She is flushed, anxious, and restless. Her BP has dropped from 135/75 to 105/55, and her temperature is 39.2ºC.

Question 3.1: What is your preliminary diagnosis?

The tachypnea, elevated temperature, and hypotension all imply sepsis. Given that this patient has undergone a long and complicated surgical procedure, bacterial infection related to the surgery (i.e., a nosocomial infection) might well be the cause of her apparent sepsis.

Question 3.2: How should you handle this situation?

Blood cultures should be ordered to look for bacteremia and to identify the causative agent (if possible). Antibiotic treatment should be started immediately, using a regimen that is likely to be effective against a broad range of Gram-positive and Gram negative bacteria. Intravenous fluids can be introduced rapidly, in order to bring her blood pressure back up.

Case History - Part II

The patient's condition worsens despite your efforts. The following morning, she is short of breath and there is excess fluid throughout her lungs. Intravenous fluids are cut back, and a vasopressor is now required to maintain her blood pressure. Because of this, she is transferred to the SICU for monitoring. To better assess her hemodynamic status, the superior vena cava (Shiley catheter) and one of the pulmonary arteries (Swan-Ganz catheter) are catheterized (the latter via the jugular vein, right atrium, and right ventricle). The patient turns out to have a cardiac output nearly double the normal for a resting adult of her size. Over the next 24 hrs, the patient continues to do poorly. Her urine output decreases almost to zero, and she requires mechanical ventilation to maintain oxygenation. She becomes increasingly edematous. The blood cultures taken earlier are negative.

Question 3.3: What is going on here?

The patient continues to display signs of severe sepsis, which may be increasing in its severity, despite the continued administration of broad-spectrum antibiotics that are normally very effective in cases like this-a seemingly nonsensical situation. It is possible that the causative agent is just unusually resistant to these antibiotics, but that seems unlikely if they have a good "track record" in this hospital. Another possibility is that there is some unexpected ongoing source of bacteria or (more likely, considering the negative blood cultures) bacterial chemical substances that provoke a severe sepsis response. She is going into multiple organ failure.

Question 3.4: What can you do to resolve this case?

The problem is most likely related in some way to the patient's complicated surgical procedure. Her external surgical wound does not appear to be infected, so the problem must be internal. As a result, exploratory surgery will be required to identify the specific source of bacteria or bacterial chemical compounds, if that is what's happening here. In this case, the exploratory surgery shows that the suture line attaching the ileum to the colon is partially disrupted, with leakage of bowel contents, intense inflammation of the mesentery, and early abscess formation.

Question 3.5: How should this patient be treated now?

Appropriate repairs must be made during surgery. Drains should be inserted to clear out the abscessed areas. Antibiotic treatment should be continued as well. In this case, the patient recovered slowly but completely. Her blood cultures remained negative.

Question 3.6: What was the most likely causative agent?

This was probably a mixed infection, caused by a variety of Gram negative colonic bacteria like Escherichia coli and other Enterobacteriaceae, anaerobes such as Bacteroides fragilis, etc.

Question 3.7: In cases like this, why does BP fall despite high cardiac output?

Blood pressure falls because of massive peripheral vasodilation, which is caused by interleukins, bradykinin, serotonin, histamine, platelet-activating factor, endorphins, complement components, endothelial relaxing factor, and/or other compounds released by host cells (such as macrophages) when they are stimulated by the presence of certain bacterial chemical substances (i.e., signaling compounds). This leads to "capillary leak" with increasing edema. The combination of very low blood pressure (which is defined as < 90 mm Hg systolic or < 40 mm below baseline) and a high cardiac output has been called "warm shock" because the patient has warm or even flushed skin, in contrast to other common forms of shock. The term "shock" is this unusual situation refers to the fact that, despite a high cardiac output, inadequate perfusion of selected vascular beds occurs, especially in the kidney, liver, and gut. The lack of perfusion in some vascular beds is called distributive shock. Sometimes, cardiac output falls late in the course of sepsis, and peripheral vasodilation is replaced by vasoconstriction. The skin becomes pale and cold, the hands and feet are bluish-purple, and the patient expires in "cold shock", like that seen after a massive heart attack or hemorrhage. However, it is also possible to die of sepsis before reaching this advanced stage.

Question 3.8: What else could have happened if this case went unresolved?

In protracted cases of sepsis, such as those complicating abdominal surgery, one organ after another may fail. This condition is called multi-organ dysfunction syndrome (MODS). Affected organs may include the following:

1. Brain: patients are often confused, delirious, stuporous, or comatose.

2. Heart: myocardial contractility is depressed; the heart compensates by dilating and beating faster, thereby increasing cardiac output. Compensatory mechanisms fail in some patients, and cardiac output drops to low levels shortly before death.

3. Clotting system: endothelial damage can lead to extensive microvascular thombosis (DIC; disseminated intravascular coagulation).

4. Kidneys: acute renal failure occurs as a result of acute tubular necrosis.

5. Lungs: the capillaries are generally leaky during sepsis, causing fluid to exude in the interstitium and alveolar spaces. The lung becomes soggy and stiff, and adequate gas exchange is impossible (adult respiratory distress syndrome; ARDS).

6. Liver: stasis of bile, focal necrosis, and jaundice are common.

7. GI tract: hemorrhagic necrosis of the mucosa occurs, probably in part because of ischemia. Loss of mucosal integrity can lead to hemorrhage.

8. Endocrine and metabolic effects: sepsis is a catabolic state that involves massive lipolysis, proteolysis, and glycogenolysis. Stress hormones (e.g., cortisol and catecholamines) circulate in high levels. An abnormally high proportion of the oxygen sent to tissues is returned to the heart unused, either because some vascular beds are not perfused or because some of the cells are too impaired (metabolically) to use the oxygen they receive. Either way, in the absence of a functioning Krebs Cycle, glycolysis occurs at a high rate and the pyruvic acid formed is reduced to lactic acid, which results in lactic acidosis.

9. Vasculature: massive peripheral vasodilation, etc. (see answer to Question 3.7, above).