The following cases and commentary, which focus on sepsis, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 17).
Case 1: Resuscitation fluid selection
A 65-year-old woman is hospitalized for pneumonia and sepsis. She has no pertinent personal or family medical history and takes no medications.
On physical examination, the patient is intubated and mechanically ventilated. Temperature is 39.0 °C (102.2 °F), blood pressure is 90/60 mm Hg, pulse rate is 100/min, and respiration rate is 24/min. Estimated central venous pressure is 6 cm H2O. Central venous oxygen saturation is 60%.
Intravenous fluid resuscitation is to be initiated.
Which of the following resuscitation therapies is contraindicated in this patient?
B. Hydroxyethyl starch
C. Isotonic crystalloids
D. Lactated Ringer solution
Case 2: Infection with femoral vein catheter
A 58-year-old woman was hospitalized 1 week ago for acute-on-chronic kidney injury. Since her hospitalization, she has been receiving hemodialysis through a temporary femoral vein catheter. Last night, she developed a fever of 38.7 °C (101.7 °F).
On physical examination today, she is confused. Blood pressure is 76/40 mm Hg and pulse rate is 108/min. Weight is 60 kg (132 lb). She has adequate peripheral venous access and is given a 1000-mL bolus of intravenous normal saline over 30 minutes. After receiving the fluid bolus, blood pressure is 78/44 mm Hg. Oxygen saturation is 96% breathing ambient air. Cardiac examination reveals an S1 and S2 with regular tachycardic rhythm. There is no jugular venous distention, murmur, or gallop. The chest is clear to auscultation. Erythema without purulent discharge is noted at the femoral catheter site. The extremities are warm with bounding pulses and without edema.
Laboratory studies show hemoglobin 9.8 g/dL (98 g/L) (baseline 10 g/dL [100 g/L]), leukocyte count 16,000/µL (16 × 109/L), creatinine 2.6 mg/dL (229.8 µmol/L), and potassium 5.6 mEq/L (5.6 mmol/L).
A blood culture obtained yesterday is growing gram-positive cocci.
A chest radiograph is normal. Electrocardiogram shows sinus tachycardia and no acute ischemic changes.
In addition to replacing the hemodialysis catheter, which of the following is the most appropriate next step in treatment?
A. Administer another 1000-mL normal saline fluid bolus
B. Initiate dobutamine infusion
C. Insert a central venous catheter
D. Transfuse one unit of packed red blood cells
Case 3: Postdischarge difficulties
A 49-year-old woman is evaluated after discharge from the hospital following treatment in the ICU for 6 days for severe sepsis with septic shock requiring aggressive fluid resuscitation and vasopressor support in addition to antibiotic therapy. She feels significantly better since returning home but has had difficulty sleeping. She works as a university professor and has been experiencing anxiety and difficulty with multitasking and other simple cognitive tasks, such as setting up and coordinating meetings with her faculty. She has been able to resume some of her hobbies, including taking short hikes and gardening, but she continues to be limited by fatigue and weakness.
On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 115/65 mm Hg, pulse rate is 80/min, and respiration rate is 10/min. BMI is 23, which is an improvement since discharge when BMI was 20. Motor strength is mildly decreased in the major muscle groups and reflexes are normal. Cardiac and pulmonary examinations are unremarkable.
Laboratory studies, including a complete blood count, basic chemistry tests, thyroid-stimulating hormone, and urinalysis, are normal.
Which of the following is the most likely cause of this patient's symptoms?
A. Critical illness neuromyopathy
B. Debilitation after prolonged bed rest
C. Generalized anxiety disorder
D. Postintensive care syndrome
Case 4: Acute kidney injury
A 62-year-old man was admitted to the ICU 3 days ago with community-acquired pneumonia complicated by septic shock and acute respiratory distress syndrome. In the past 24 hours, his fever and lactic acidosis have resolved, and the patient no longer requires vasopressors to maintain adequate blood pressure. However, he has become oliguric and is requiring higher FiO2 and positive end-expiratory pressure (PEEP) to maintain oxygenation. He is receiving normal saline maintenance fluid at 100 mL/h. The net fluid balance since admission is positive 8.2 L. His current medications are ceftriaxone, azithromycin, and propofol.
On physical examination, temperature is 37.1 °C (98.8 °F), blood pressure is 92/52 mm Hg, pulse rate is 88/min, and respiration rate is 28/min; BMI is 26. Oxygen saturation is 91% on an FiO2 of 0.8 and a PEEP of 16 cm H2O. Mentation seems clear, and the skin is warm. Central venous pressure is 17 cm H2O. Cardiac examination reveals a regular rhythm without gallop or rub. Chest examination reveals diffuse inspiratory crackles with decreased breath sounds at the bases. There is pitting edema present in all extremities.
Laboratory studies show creatinine 2.2 mg/dL (194.5 µmol/L) (baseline 1.2 mg/dL [106.1 µmol/L]) and potassium 4 mEq/L (4 mmol/L). Arterial blood gases reveal pH 7.30, PCO2 50 mm Hg (6.7 kPa), and PO2 86 mm Hg (11.4 kPa). A chest radiograph shows bilateral infiltrates and interval development of small bilateral pleural effusions.
Which of the following is the most appropriate next step in treatment?
A. Administer 250 mL of 5% albumin every 6 hours
B. Discontinue intravenous maintenance fluids
C. Initiate continuous venovenous hemodialysis
D. Start hydrocortisone
Case 5: Difficulty weaning from ventilation
A 25-year-old woman is evaluated in the ICU for difficulty in weaning from mechanical ventilation. Medical history is significant for type 1 diabetes mellitus, and she was admitted to the ICU 8 days ago with diabetic ketoacidosis secondary to sepsis from a rectal abscess. Her hospital stay has been prolonged and complicated. Her medications are piperacillin/tazobactam and basal and bolus insulin.
On physical examination, vital signs are normal. Neurologic examination reveals a weak hand grip and difficulty raising her arms. Reflexes are present but reduced.
Which of the following is the most likely diagnosis?
A. Diabetic neuropathy
B. Guillain-Barré syndrome
C. ICU-acquired weakness
D. Vasculitic neuropathy
Answers and commentary
Correct answer: B. Hydroxyethyl starch.
Resuscitation therapy with hydroxyethyl starch (HES) is most likely to lead to the development of acute kidney injury (AKI). This patient has septic shock and requires fluid resuscitation to prevent or limit multi-organ failure and reduce mortality. Repetitive fluid challenges are performed by giving a 500- to 1000-mL bolus of crystalloid over short intervals while assessing response to target central venous pressure. Most patients need 4 to 6 L of fluid in the first 6 hours, and a frequent error is underestimating the intravascular volume deficit and the amount of fluid required. The fluid input is typically greater than output owing to vasodilation and capillary leak. HES is a synthetic colloid that is associated with an increased risk of AKI, increased requirement of renal replacement therapy, a trend toward increased blood product transfusion, and increased mortality. HES accumulates in the proximal renal tubular epithelial cell, resulting in vacuolization and swelling of the proximal renal tubular cell, tubular obstruction and injury, and an osmotic nephrosis. As a result, the 2013 Surviving Sepsis Campaign recommends against using any HES in patients with severe sepsis.
Volume resuscitation can be achieved with either crystalloid or colloid solutions. The crystalloid solutions are lactated Ringer solution and 0.9% sodium chloride; the colloid solutions include albumin. Evidence from randomized trials and meta-analyses have found no convincing difference between using crystalloid solutions such as normal saline and lactated Ringer and albumin solutions in the treatment of severe sepsis or septic shock; however, colloid is far more expensive.
- Hydroxyethyl starch is associated with an increased risk of acute kidney injury, increased requirement of renal replacement therapy, a trend toward increased blood product transfusion, and increased mortality and is not recommended in patients with severe sepsis.
Correct answer: A. Administer another 1000-mL normal saline fluid bolus.
The most appropriate next step in treatment is to administer another 1000-mL normal saline fluid bolus. This patient's findings are highly compatible with septic shock from a catheter-related bloodstream infection based on her fever, hypotension, organ failure (encephalopathy), and bacteremia. Aggressive fluid resuscitation and early administration of antibiotics are the highest priorities in managing septic shock. After receiving 1000 mL of fluid, this patient has no evidence of volume overload despite her known kidney injury, and a second bolus of fluid is indicated. Patients with sepsis typically need multiple fluid boluses to achieve adequate intravascular volume repletion.
Dobutamine is not appropriate because this patient's clinical picture is indicative of septic, rather than cardiogenic, shock. There are no changes on electrocardiogram, she has warm extremities consistent with a low systemic vascular resistance state, and she has signs of infection. Dobutamine is included in early goal-directed therapy protocols, but it is appropriate only after confirming adequate intravascular volume repletion. Also, the recent ProCESS trial calls into question dobutamine use in the absence of confirmed cardiac dysfunction.
The ProCESS trial included 31 emergency departments in the United States that were randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based early goal-directed therapy (EGDT); protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. Protocol-based resuscitation of patients in septic shock did not improve outcomes. In April 2014, the National Quality Forum downgraded use of central venous lines in the resuscitation of patients with septic shock to be at the discretion of clinicians. Because this patient has adequate peripheral venous access, the placement of a central venous catheter is not a priority management step.
Blood transfusion is not appropriate because this patient's stable hemoglobin level and manifestations of sepsis reliably exclude hypovolemic shock from acute blood loss. Crystalloids are the preferred choice for initial resuscitation of patients with sepsis because of their ready access, ease of rapid infusion, safety profile, and low cost. The efficacy of protocol-based blood transfusion as part of early goal-directed therapy is unclear given the results of the ProCESS trial.
- Aggressive fluid resuscitation and early administration of antibiotics are the highest priorities in managing septic shock; the routine use of central venous catheters, inotropic drugs, and blood transfusion does not improve outcomes in patients with septic shock.
Correct answer: D. Postintensive care syndrome.
The most likely diagnosis is postintensive care syndrome. The patient was severely ill and in an ICU for several days where she was treated for severe sepsis and shock. Postintensive care syndrome is a term used to describe new or worsening function in one or more physical, cognitive, or mental domains that persists after hospital discharge following a critical illness, as in this patient. Examples of clinical findings include cognitive deficits resembling traumatic brain injury or mild cognitive impairment; psychiatric symptoms such as depression, anxiety, and posttraumatic stress disorder (PTSD); and physical deficits such as weakness and fatigue. Although the cause of this syndrome is not understood, possible mechanisms include hypoxia, hypotension, inflammation, the catabolic state, hypoglycemia, other nutritional disorders, immobility, and agents used for sedation. This syndrome may also be applied to symptoms experienced by family members of post-ICU patients who may experience sleep disturbances, anxiety, depression, a complicated grief reaction, and PTSD. The efficacy of preventive measures and treatment interventions is not known, but efforts to maintain light sedation and avoid glycemic extremes and hypoxia may be of benefit. Treatment otherwise focuses on the specific symptoms experienced by the patient or family.
Critical illness neuromyopathy is a generalized axonal sensorineural polyneuropathy associated with severe illness and treatment in an ICU setting. Although it could explain this patient's physical limitations, it is not associated with psychiatric symptoms such as anxiety or cognitive deficits such as difficulty multitasking.
Similarly, prolonged bed rest in patients in the ICU may result in significant deconditioning and physical limitations following recovery from acute illness; however, it would not be expected to cause problems with psychiatric or cognitive function.
Patients treated in the ICU for severe illness are at increased risk for depression, anxiety, and PTSD, which may result in the psychiatric and cognitive symptoms seen in this patient. Generalized anxiety disorder develops over time and is characterized by excessive worrying about many things of little or no need for concern. Sleep disturbances along with anxiety are reasons patients seek help from their physicians. However, this diagnosis would not explain this patient's overall symptom complex, which includes cognitive limitations and physical symptoms such as weakness.
- Postintensive care syndrome is a term used to describe new or worsening function in one or more physical, cognitive, or mental domains that persists after hospital discharge following a critical illness.
Correct answer: B. Discontinue intravenous maintenance fluids.
The most appropriate next step in treatment is to discontinue intravenous maintenance fluids and perhaps start a trial of diuretics. This patient is well past the window (within the first several hours after diagnosis) in which early aggressive fluid resuscitation is known to be beneficial in septic shock. Although individual markers of volume status are imperfect, the combination of a normalized lactic acid level, substantial positive fluid balance, improved blood pressure, and elevated central venous pressure suggest that the patient is euvolemic if not hypervolemic. Additional fluid resuscitation is unlikely to improve kidney function, may make it worse, and could exacerbate this patient's hypoxemia given his acute respiratory distress syndrome and pleural effusions.
Albumin is unlikely to be beneficial and may cause harm in a patient who is in the recovery phase of septic shock and has evidence of intravascular volume overload. Administration of colloids offers no advantage over crystalloids in resuscitating critically ill patients in general; however, sepsis guidelines note that albumin may be advantageous in patients with refractory shock not responding to crystalloids.
Hemodialysis is not clearly indicated at this time. Some concern exists that this patient is developing intravascular volume overload, but reducing intravenous fluids, avoiding nephrotoxins, and perhaps starting a trial of diuretics would be appropriate first steps. This patient does not have other indications for dialysis such as hyperkalemia, uremia, or severe acidosis. His declining kidney function is likely from the residual effect of acute tubular necrosis and may improve in the next few days now that his septic shock is resolving.
Studies of stress-dose glucocorticoids have not consistently shown benefit in patients with septic shock. Their use is generally reserved for patients with persistent shock despite fluid resuscitation and vasopressor support.
- In patients with septic shock, aggressive fluid resuscitation after the early resuscitation phase (within the first several hours after diagnosis) can be detrimental.
Correct answer: C. ICU-acquired weakness.
The most likely diagnosis is ICU-acquired weakness. ICU-acquired weakness includes critical illness polyneuropathy (with axonal nerve degeneration) and critical illness myopathy (with muscle myosin loss), resulting in profound weakness. These two conditions are difficult to differentiate and may overlap. Some experts recommend that biopsies and more formal electrophysiologic studies be reserved for patients in whom the diagnosis is more ambiguous and where other diagnoses are more likely to exist. ICU-acquired weakness is associated with long-term functional disability, prolonged ventilation, and in-hospital mortality. Risk factors include female sex, hyperglycemia, sepsis, multiple organ dysfunction and systemic inflammatory response, immobility, and long duration of mechanical ventilation. Strategies to limit or prevent ICU-acquired weakness include sedation limitation, early mobilization, and moderate glucose control. The strategies that have the most impact are not yet known.
Diabetes predisposes to multifactorial nerve injury due to nerve compression, ischemia, inflammation, and metabolic changes. Distal sensorimotor peripheral neuropathy is the most common disorder and presents with numbness, tingling, and burning pain in a stocking-glove distribution. Weakness may occur late in the course of the disease. However, this pattern is not present in this patient and would be unlikely to account for this patient's symmetric muscle weakness.
Guillain-Barré syndrome is the most common cause of acute diffuse neuromuscular paralysis. Affected patients initially experience rapid onset of symmetric weakness of the upper and lower limbs over days to weeks, generally in the setting of a recent infection, trauma, or surgery. The disorder generally progresses over 2 weeks, with 90% patients at their worst by 4 weeks. Although many patients describe paresthesias or neuropathic pain in the hands and feet, objective sensory loss is usually mild or absent. Neurologic examination reveals weakness and decreased or absent deep tendon reflexes. The time course and absence of paresthesias in this patient make Guillain-Barré syndrome an unlikely diagnosis.
Vasculitic neuropathy is usually found in association with a systemic vasculitis that involves other organs (skin, lungs, kidneys), but it can be found in isolation. Patients most commonly present with both sensory and motor nerve dysfunction that is asymmetric and distal, typically involving the longest nerves of the body first. This patient's painless and symmetric loss of muscle function is not compatible with vasculitis neuropathy.
- ICU-acquired weakness includes critical illness polyneuropathy (with axonal nerve degeneration) and critical illness myopathy (with muscle myosin loss), resulting in profound weakness; it may impair weaning from the ventilator.