Pamela A. Lipsett
Presentation
A 68-year-old man presents to the emergency department with severe acute abdominal pain located in his left lower quadrant for the last 2 days. He has had a fever to 101°C, diarrhea 4 days ago, and now constipation for the last day. He has not vomited, but he has been nauseated and has been unable to take solid food or liquids. He has made little urine in the last day. He reports a history of acute diverticulitis requiring two previous hospitalizations in the last year and hypertension controlled with medication. He is unable to give a more complete history because of increasing confusion. His vital signs reveal an elevated temperature to 101.5°C, a pulse of 128, a respiratory rate of 32, and a blood pressure of 74/38 mm Hg. His examination demonstrates an acutely ill appearing man in pain and respiratory distress. He is mildly confused but without focal neurologic findings. He is tachypneic with rapid shallow respiratory efforts but clear lungs. His oxygen saturation is 90% on 60% face mask. His cardiac examination is normal save for his depressed blood pressure and elevated heart rate. His abdominal examination reveals a distended abdomen that is rigid and painful to palpation both generally and especially in the left lower quadrant where there is a suggestion of fullness. His stool is guaiac negative. His extremities are cool with pulses not palpable.
Differential Diagnosis
As is often the case, two issues must be immediately addressed; the patient is in shock and the shock is most likely related to the abdominal pain. The magnitude of the systemic illness suggests that this patient has an abdominal catastrophe. With a rigid abdomen and signs of shock, the possibility of a perforated viscous with intra-abdominal contamination is considered as well as all of the more general causes of peritonitis. In this age group, the most common etiologies of a rigid abdomen and pneumoperitoneum are related to diverticulitis, a perforated ulcer, or even appendicitis. A history of diverticulitis makes this diagnosis most likely, but the broad differential related to an acute abdomen must be considered. Identification of the specific etiology and source control is an essential element of ultimate treatment for this patient, but he has signs and symptoms of shock, which must be addressed expeditiously.
Shock is defined as inadequate tissue perfusion. While shock maybe classified in many ways, it is commonly classified as shown in Table 1. With the history of poor intake and diarrhea, this patient may have had an element of dehydration, but it is unlikely that his very depressed blood pressure is entirely due to hypovolemia. Of note, his diastolic pressure is quite low suggesting vasodilatation rather than vasoconstriction. Moreover, the combination of fever and abdominal pain suggests infection due to abdominal contamination and resulting distributive (i.e., septic) shock. Due diligence in considering cardiac and noncardiogenic causes is appropriate; however, investigation should not delay action in ensuring resuscitation. Further studies are required to address the etiology of shock and to define the most likely contributing cause.
TABLE 1. Differential Diagnosis of Shock
Workup
Laboratory evaluation demonstrates an elevated white blood cell (WBC) count of 24,000/mm3, hemoglobin of 15.0 g/dL, and a depressed platelet count of 100,000. Electrolytes reveal a sodium of 142, potassium 3.4, chloride 100, bicarbonate 20, glucose 180 mg/dL, blood urea nitrogen 48, and serum creatinine of 1.8 mg/dL. Lactate is elevated to 4.9, arterial blood gas is 7.30/30/60. A plain radiograph is fairly unremarkable. A computerized tomographic (CT) scan without contrast demonstrates an inflammatory mass in the sigmoid colon with pericolonic fluid extending into the pelvis and a small amount of localized free air adjacent to the colon. A cardiogram shows sinus tachycardia without acute changes. A chest radiograph shows a modest respiratory effort, but clear lungs.
Discussion
The Surviving Sepsis Campaign (SSC) has defined two endpoints for consideration in the treatment of septic shock: one to be completed by 6 hours (the resuscitation bundle) and one by 24 hours (the management bundle). The composition of these bundles recommended in the SSC guidelines is shown in Table 2. Notably, the SSC guidelines last published in 2004 are currently being revised and are expected for publication within the next year. Based on studies that have been published since 2004, it is very likely that the degree of support for some of the prior recommendations will change and new recommendations will follow.
TABLE 2. Surviving Sepsis Bundle Components
Use of the elements of the SSC or “bundle” has decreased mortality from more than 50% to as low as 37.5%. Further details of management of septic shock will be discussed in the next section. Source control for intra-abdominal sepsis while essential and important is secondary to the initial resuscitation and stabilization of a patient in septic shock. The description of the CT scan suggests that this patient has Hinchey stage III disease (Table 3), and an intervention will be required once he has been resuscitated. While open surgery has classically been applied to the treatment of complicated diverticulitis, staged percutaneous treatment with one-staged repair has been reported with increasing success, as high as 91% of patients in a recent report.
TABLE 3. Hinchey Stage for Diverticulitis
Diagnosis and Treatment
Severe sepsis is defined as the presence of infection and end-organ dysfunction, hypoperfusion, or hypotension. Septic shock is one step further into critical illness with refractory hypotension or hypoperfusion in spite of adequate fluid administration. Signs of systemic hypoperfusion in this case include an elevated serum lactate (>4 mm/L), oliguria, mental confusion, and a decreased PaO2/FIO2 ratio (60/60 = 100). The patient should be approached with therapies consistent with the SSC guidelines. Given the poor condition of the patient at presentation, immediate attention should be focused on support of his respiratory effort with additional oxygen (100% face mask). He is likely to require intubation and mechanical ventilation to decrease the work of breathing and to administer additional positive pressure given his very poor and concerning PaO2/FIO2 ratio. Adequate intravenous (IV) access must be obtained and fluids should be rapidly administered to restore blood volume, which is decreased from antecedent volume loss from diarrhea, poor oral intake, and capillary leak with loss into the peritoneal cavity and into the microcirculation. His metabolic acidosis must be reversed. Isotonic fluids (or colloids) should be administered to restore blood volume and perfusion pressure. The SSC guidelines suggest that the central venous pressure should be >8 mm Hg. A meta-analysis of 29 studies published in 2008 found among early resuscitation studies quantitative or goaldirected resuscitation when compared with standard resuscitation resulted in a significant decrease in mortality (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.37 to 0.69). However, while the use of SVO2 is suggested by the SSC guidelines, this is not universally accepted. A large trial of patients with adult respiratory distress syndrome (ARDS) did not demonstrate any benefit of a pulmonary artery catheter over a central venous catheter.
If the patient remains hypotensive after fluid resuscitation, vasopressors are typically added. The SSC guidelines suggest that either dopamine or norepinephrine is an appropriate agent. More recently, a randomized controlled trial compared dopamine versus norepinephrine in 1,629 patients with shock, the majority with sepsis. While there was no difference in mortality between the two groups, the incidence of adverse events (arrhythmias) was significantly greater in the dopamine group. The role of vasopressin in the treatment of septic shock is less certain as a large randomized trial did not show any benefit in mortality but did show that vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock.
Following the acquisition of blood cultures, patients who are in septic shock should have broad-spectrum antibiotics administered in short order (<1 hour). For the patient in this scenario, expected pathogens include enteric gram-negative bacteria, facultative aerobic gram-positive organisms, and anaerobes. Resistant pathogens are unlikely to be present in the patient described. However, patients who develop septic shock in the hospital, after recent hospitalization or following a stay in a long-term care facility, are all at increased risk of resistant pathogens. Empiric selection of antibiotics should consider epidemiologic risk factors noted. Depending on the etiology of septic shock, appropriate initial antibiotic selection has been linked to improved survival; thus, broad-spectrum agents are initially selected. The Surgical Infection Society guidelines for intra-abdominal infections of moderate to severe severity would indicate that several choices of antibiotics would be appropriate for the case patient. For single agents, these would include imipenem-cilastatin, meropenem, doripenem, and piperacillin–tazobactam. Experts should be familiar with the pharmacodynamic and kinetic issues of antibiotic administration in critically ill patients. Hospital systems should be organized so that a patient who has just been identified as having septic shock can rapidly receive appropriate antibiotics. Administration of antibiotics within 1 hour has been demonstrated to have a significant survival benefit.
One of the controversial issues in the management of patients in septic shock is whether a critically ill patient should receive low-dose steroids (<300 mg of hydrocortisone). While there are conflicting trials on the subject, the SCC guidelines recommend the use of steroids for a short period (7 days) in patients with septic shock who are unresponsive to fluids and vasoactive agents. Current data would suggest that patient survival is not changed when using steroids, but that time requiring vasopressors is reduced when hydrocortisone is used. An adrenal stimulation test is not required and administration of steroids may be beneficial when used for more than 100 hours but <7 days. Fludrocortisone does not appear to be necessary.
Currently, the use of activated protein C (APC) is recommended by the SSC guidelines for patients who qualify by severity of illness and who do not have a contraindication. However, more recent data from clinical trials and a Cochrane Collaborative concluded that APC did not reduce the risk of death in adult patients with severe sepsis (pooled RR: 0.97, 95% CI: 0.78, 1.22). Further APC use was associated with an increased risk of bleeding (RR: 1.47, 95% CI: 1.09, 2.00). It seems unlikely that APC will be included in the next SSC update.
The control of blood glucose has undergone much study and debate over the last decade. While tight glucose control (80 to 110 mg/dL) appeared to be of significant benefit to patients when considering both survival and morbidity, more recent studies have not demonstrated overall survival benefit and have suggested significant harm secondary to hypoglycemia episodes when glucose is controlled too tightly. Thus, a target glucose of <150 seems appropriate.
Patients with severe sepsis and septic shock are likely to develop respiratory failure ARDS. Should a patient develop ARDS, low tidal volume (<6 mL/kg of predicted body weight) with management of the ventilator to achieve an inspiratory plateau pressure of <30 cm H2O has been shown to improve survival. This is an element of treatment that has not been well translated into clinical practice but has strong data supporting improved survival.
Once this patient has had adequate resuscitation, source control of the intra-abdominal process must be achieved. The specific surgical management of a patient with complicated diverticulitis is presented in an earlier chapter. Given the severity of this patient’s presentation, a staging temporizing procedure with percutaneous drainage would be an appropriate initial treatment in many patients.
Special Considerations
Some patients with complicated diverticulitis will present with Hinchey stage IV disease with gross fecal contamination. Patients in this category will need rapid resuscitation, operative intervention, and source control. One study suggested that survival is improved when source control occurs within 6 hours.
Patients who develop sepsis and septic shock following a surgical procedure often show warning signs that can be identified by careful observation of their postoperative course. Typically in a patient who is developing a complication, the normal postoperative ebb and flow metabolism is disrupted, and patients may be identified by an extraordinary initial stress response and fluid requirement, failure to diurese in a timely fashion, and signs of infection developing such as worsening glucose control, mental confusion or delirium, rising WBC, and fever. These high-risk patients should undergo a careful examination and directed laboratory and radiograph studies as appropriate.
Patients with end-organ dysfunction or failure at baseline are at increased risk of death following an episode of sepsis or septic shock. Management of patients in this group should carefully consider known organ failure and selection of strategies for support streamlined appropriately. For example, patients with cardiac disease at baseline and poor ejection fraction may need early beta agonist support, though attempts at establishing supranormal oxygen delivery do not appear warranted. Another important consideration is a patient with worsening renal function who develops septic shock. While searching for a source of infection a CT scan may seem appropriate, the use of IV contrast should be very carefully considered as to the risk benefit relationship in what additional information the IV contrast may infer versus the harm of IV contrast when a patient already has compromised renal blood flow due to shock. This is especially important when the presentation of an acute pulmonary embolus may be confused with septic shock. Often the discriminating feature is that sepsis is not “suddenly occurring,” and often the antecedent signs mentioned above have been present but are unrecognized.
Postoperative Management
Once a patient is stabilized, source control should be obtained. This can be accomplished by percutaneous drainage in many patients, while open surgery will be required in some. For patients with a closed space infection such a cholangitis or pyelonephritis, early drainage and decompression is necessary if the patient remains unstable. In patients in whom a device is associated with the septic source, the device (e.g., central line) may need to be removed as part of the treatment algorithm.
Ongoing support in an ICU is needed following intervention until organ dysfunction has resolved. While the exact duration of antibiotics will depend on source and degree of source control, with the exception of endovascular infections, the need for antibiotics beyond 14 days suggests inadequate source control or a secondary infection or complication. Most patients will require 5 to 10 days of antibiotics with an ongoing study to identify whether a time-based treatment philosophy or symptom-based (resolution of fever, WBC, local signs) should dictate duration of therapy for complicated intra-abdominal infections.
Case Conclusion
This patient was intubated initially and placed on ARDS protocol settings. He received 14 L of crystalloids in addition to norepinephrine to support intravascular volume and blood pressure. Following blood cultures, piperacillin–tazobactam was administered within 1 hour of his presentation. His urine output improved from 5 to 10 mL/h to 35 mL/h before he went to interventional radiology for percutaneous drainage of his pelvic abscess. Within 4 hours of his drainage procedure while receiving ongoing fluid, his norepinephrine requirement abated, so steroids were not administered. His ventilatory requirement continued for the next 3 days, but following a spontaneous breathing trial on day 4, he was successfully liberated from the ventilator. He began to spontaneously diurese on day 2.5 and was assisted with diuretics to remove the fluid (total 20 L) he had gained while in shock. He was transferred to the ward for rehabilitation on day 5 after presentation in septic shock.
TAKE HOME POINTS
· A patient with shock should be recognized immediately and treatment begun based on first principles.
· Support of failing or dysfunctional organ systems should be a treatment priority based on typical priorities of airway, breathing, and circulation. This often means that the patient should receive the administration of oxygen, mechanical ventilation, and aggressive administration of fluids, vasoactive agents, and antibiotics.
· Surviving sepsis guidelines provide evidence-based treatment strategies that are based on 6-and 24-hour time points. These guidelines will be updated in 2012.
· Initial resuscitation should precede any attempt at source control beyond antibiotic administration.
SUGGESTED READINGS
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. N Engl J Med. 2000;342(18):1301–1308.
De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362:779–789.
Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004;30(4):536–555.
Dharmarajan S, Hunt SR, Birnbaum EH, et al. The efficacy of nonoperative management of acute complicated diverticulitis. Dis Colon Rectum. 2011;54:663–671.
Ferrer R, Artigas A, Levy M, et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299(19):2294–2303.
Jones AR, Brown MD, Trzeciak S, et al. The effect of quantitative resuscitation strategy on mortality patients with sepsis: a meta-analysis. Crit Care Med. 2008;36(10):2734–2739.
Marti-Carvajal AJ, Sola I, Lathyris D, et al. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev. 2011;(4):CD004388.