MKSAP: Sedation and ventilation

The following cases and commentary, which address sedation and ventilation, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP14).

Case 1: Septic shock and acute respiratory failure

A 31-year-old woman was admitted to the ICU ten days ago because of septic shock, acute respiratory failure and acute respiratory distress syndrome as a result of pneumococcal pneumonia. Her cardiopulmonary status is steadily improving. She still requires mechanical ventilation but has been afebrile for 24 hours and is hemodynamically stable without vasopressors. Current medications are levofloxacin, lorazepam infusion, fentanyl infusion, subcutaneous heparin, and ranitidine. She is also receiving bolus tube feedings.

The volume-cycled ventilator is on minimal settings (volume control set rate, 16; tidal volume, 400 mL; FiO2, 40%; positive end-expiratory pressure, five cm H2O). A spontaneous breathing test was halted after 15 minutes because her respiration rate decreased to 5 to 10 breaths per minute.

On physical examination, temperature is 36.4°C (97.5°F), blood pressure is 134/88 mm Hg, pulse rate is 86 beats/min, and respiration rate (on the ventilator) is 16 to 18 breaths/min. Bronchial breath sounds are auscultated at the left base. Cardiovascular examination is normal. On neurologic examination, the patient is sedated with minimal response to tactile stimulation. The leukocyte count is 12,500/µL (12.5 × 109/L) (decreased from 19,000/µL [19 × 109/L]). A chest radiograph shows resolving acute respiratory distress syndrome with continued dense consolidation in the left base and no pleural effusion.

In addition to continued daily spontaneous breathing trials, which of the following is the most appropriate management?

A. Changing to synchronized intermittent mandatory ventilation.
B. Laryngoscopic evaluation of the vocal cords.
C. Pairing spontaneous awakening trials with spontaneous breathing trials.
D. Tracheostomy.

View correct answer for Case 1

Case 2: Neisseria meningitidis meningitis

A 19-year-old woman is admitted to the intensive care unit because of Neisseria meningitidis meningitis. Penicillin G and cefepime are initiated. Given her poor mental status and an inability to protect her airway, she requires intubation and mechanical ventilation plus propofol sedation. Intravenous fluids and norepinephrine are needed to treat refractory hypotension, and she is also treated with subcutaneous heparin, 5,000 units every eight hours, and ranitidine for deep venous thrombosis and peptic ulcer prophylaxis, respectively.

On hospital day two, norepinephrine is discontinued. She remains sedated with propofol while on the ventilator. On hospital day three, she develops aspiration pneumonia and antibiotics are broadened. Increasing doses of propofol (4 mg/kg/h) are needed to control agitation and patient- ventilator asynchrony.

By hospital day five, she develops a profound metabolic acidosis (bicarbonate 12 mEq/L [12 mmol/L]), rhabdomyolysis (creatine kinase, 21,123 U/L), oliguric brown urine, acute kidney injury (creatinine, 2.7 mg/dL [206 µmol/L]), and bradycardia. On physical examination, her temperature is 37.3°C (99.1°F), blood pressure ranges from 105/55 to 133/66 mm Hg, pulse rate ranges from 45 to 79 beats/min, and respiration rate varies from 22 to 32 breaths/min (on the ventilator). Central venous pressure is 7 to 8 mm Hg. Coarse breath sounds are auscultated bilaterally. Cardiac examination is normal. The patient does not respond to voice commands but intermittently withdraws from painful stimuli.

An electrocardiogram shows sinus bradycardia (rate of 56/min) with new right bundle branch block. A chest radiograph shows a dense right lower lobe pneumonia without an effusion that is unchanged from findings on yesterday's film. She remains easily oxygenated on 50% FiO2 (arterial pO2, 95 mm Hg) with stable ventilator settings from admission.

Which of the following is the most likely cause of the patient's recent deterioration?

A. Uncontrolled sepsis.
B. Neuroleptic malignant syndrome.
C. Propofol infusion syndrome.
D. Pulmonary embolism.
E. Worsening pneumonia.

View correct answer for Case 2

Case 3: Respiratory distress after bone marrow transplant

A 33-year-old man with acute myeloid leukemia is admitted to the ICU from the bone marrow transplant unit where he had received an allogeneic transplant 17 days ago. Earlier today, he learned that monocytes had appeared on his blood smear for the first time. His leukocyte count had risen from 100 to 500/µL, and it appeared that his marrow might be recovering. Within hours, he became increasingly dyspneic and hypoxemic, and a chest radiograph showed diffuse bilateral infiltrates.

On arrival in the ICU, he is in moderately severe respiratory distress; his temperature is 37.8°C (100°F), blood pressure 144/94 mm Hg, pulse rate 122 beats/min, and respiration rate 36 breaths/min. Oxygen saturation on 100% oxygen by nonrebreather mask is 88%. Neck veins are flat, and there is no peripheral edema. He is using accessory muscles of breathing; examination of the lungs reveals bilateral scattered crackles; and cardiac examination reveals no gallops or murmurs. His hematocrit had been stable at 26%, his platelet count is 26,000/µL, and he had no sputum. Broad-spectrum antibiotic therapy is started.

Which of the following would be the most appropriate next step in this patient's management?

A. Intravenous corticosteroids.
B. Continuous positive airway pressure (CPAP).
C. Bronchoscopy with bronchoalveolar lavage.
D. Noninvasive positive-pressure ventilation (NPPV).
E. Intubation.

View correct answer for Case 3

Answers and commentary

Case 1

Correct answer: C. Pairing spontaneous awakening trials with spontaneous breathing trials.

High doses of sedative agents are often needed to tolerate mechanical ventilation and minimize patient-ventilator asynchrony in patients with acute respiratory failure. However, high doses of these agents are associated with significant morbidity. Daily spontaneous breathing trials (SBTs) have become the cornerstone of ventilator liberation (weaning) protocols in ICUs and have been shown to decrease the duration of mechanical ventilation and mortality rates in the ICU. More recently, daily spontaneous awakening trials (SATs), which involve interruption of sedation, have been shown to be beneficial. However, concerns about patient comfort and safety have limited the universal use of this strategy. The Awakening and Breathing Control Trial now provides confirmatory evidence that the pairing of daily SATs with daily SBTs is safe and effective. In this multicenter randomized controlled trial, the patients in the intervention arm received a protocol of daily SATs and SBTs, and those in the control arm received usual sedation care and daily SBTs. Patients in the intervention arm spent more days breathing without mechanical assistance and had shorter ICU and hospital stays and lower mortality rates. The intervention arm had a higher number of self-extubations, but the number of patients requiring reintubation was similar between the two groups.

Synchronized intermittent mandatory ventilation (SIMV) is a mixed mode of ventilation that combines a set number of fully supported breaths with additional spontaneous breaths receiving less support. Traditionally, SIMV was used with the set breaths being volume-targeted, ensuring a minimal minute ventilation, and additional breaths over the minimum rate were unsupported. More commonly, SIMV is now set so that the patient-triggered breaths are delivered with pressure support. Although this was thought to be an ideal weaning mode, studies have demonstrated that it actually takes longer to liberate patients from the ventilator when supported by SIMV. Therefore, changing the ventilator mode to synchronized intermittent mandatory ventilation would not facilitate weaning. Patients may develop vocal cord dysfunction following prolonged intubation, but there is no indication for routine evaluation of the vocal cords in the absence of stridor or speech problems.

Timing of tracheostomy varies from patient to patient. Generally, the decision to proceed with tracheostomy is usually determined by the anticipation of prolonged mechanical ventilation (e.g., more than 14 days), a lack of progress toward weaning, or with recurrent, failed attempts at extubation. Therefore, tracheostomy is not indicated in this patient, who failed to complete only one SBT and had a definite reason (oversedation) for that failure. Although a tracheostomy may help with weaning from sedation in some patients, it is not indicated unless attempts at decreasing or stopping sedation cause unacceptable side effects in an orally intubated patient.

Key Points

  • Use of daily spontaneous awakening trials (interruption of sedation) in the intensive care unit is both safe and effective.
  • Daily spontaneous awakening trials, when paired with daily spontaneous breathing trials, are associated with shorter duration of mechanical ventilation and length of stay in the intensive care unit and lower mortality rates.

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Case 2

Correct answer: C. Propofol infusion syndrome.

This patient has severe bacterial meningitis and septic shock. She initially improves with appropriate volume resuscitation, norepinephrine and intravenous antibiotics. However, her hospital course is complicated by aspiration pneumonia that requires continued mechanical ventilation and sedation. On hospital day five, she develops new profound metabolic acidosis, rhabdomyolysis (elevated serum creatine kinase level and brown oliguric urine), acute renal failure, and cardiac instability (bradycardia, new right bundle branch block).

The most likely diagnosis is propofol infusion syndrome (PRIS), a relatively uncommon but clinically significant side effect of this drug. The clinical features of PRIS include acute refractory bradycardia, severe metabolic acidosis, rhabdomyolysis, hyperlipidemia, and acute fatty liver (the latter two are not present in this patient). The cardiac instability often leads to refractory bradycardia and asystole, which is the most common cause of death. PRIS is best described in the pediatric literature, but is now being increasingly recognized in adults. Although PRIS typically occurs following anesthesia, it can also develop in patients in ICUs and is usually associated with large infusion doses of propofol (>3 to 4 mg/kg/h) lasting 48 hours or longer. Case reports have also suggested that PRIS can occur at much lower doses and/or shorter durations.

Although the cause is unknown, PRIS may be due to direct mitochondrial respiratory chain inhibition or impaired mitochondrial handling of free fatty acids by propofol. Proposed predisposing factors include young age and central nervous system injury or infection.

Other than immediate cessation of propofol, treatment options are limited. Rhabdomyolysis is treated with volume expansion, and hypotension is managed with vasopressors and inotropes. Hemodialysis and hemoperfusion have been tried with varying success.

This patient's clinical presentation is classic for PRIS, and she seems to be recovering from the initial episode of sepsis as evidenced by her successful weaning from norepinephrine and her stable blood pressure and temperature. Although the pneumonia is a new finding, it is not the problem responsible for her recent deterioration. Her chest radiograph remains stable, and her ventilator settings have not changed. Furthermore, her aspiration pneumonia is an unlikely cause for metabolic acidosis, rhabdomyolysis, and acute kidney injury.

The neuroleptic malignant syndrome is a life-threatening disorder caused by an idiosyncratic reaction to neuroleptic tranquilizers, some antipsychotic drugs, and all drugs that cause central dopamine receptor blockade. Most patients with the syndrome develop muscle rigidity, hyperthermia, cognitive changes, autonomic instability, diaphoresis, sialorrhea, seizures, arrhythmias, and rhabdomyolysis within two weeks after initiating the drug. The diagnosis is made clinically. Death in patients with the neuroleptic malignant syndrome is from respiratory or cardiovascular failure, disseminated intravascular coagulation, or myoglobinuric acute renal failure. This patient is not taking any drug known to cause neuroleptic malignant syndrome, so this diagnosis in unlikely.

Although medical patients in critical care units have an increased risk for thromboembolism, that risk would be lessened in a young patient who is receiving appropriate prophylaxis. Patients with pulmonary embolism would have worsening hypoxia or, with massive embolism, acute right heart failure and low cardiac output.

Key Points

  • The clinical features of the propofol infusion syndrome include acute refractory bradycardia, severe metabolic acidosis, hyperlipidemia, and acute fatty liver.
  • Most reported cases of the propofol infusion syndrome in adults have been associated with large doses (>3 to 4 mg/kg/h) of propofol for extended periods of time (>48 hours).

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Case 3

Correct answer: D. Noninvasive positive-pressure ventilation (NPPV).

The patient has developed acute hypoxemic respiratory failure after bone marrow transplantation, and the differential diagnosis is large. Infectious causes such as nosocomial bacteria and such opportunistic organisms as cytomegalovirus, fungi, and Pneumocystis jirovecii must be considered. Cardiogenic and noncardiogenic forms of pulmonary edema, fluid overload, and reactions to drugs are also possible. Recurrence of leukemia with a leukoagglutination reaction is unlikely in view of the blood smear findings. A real possibility is diffuse alveolar hemorrhage, a reaction of unknown cause that occurs most often soon after bone marrow transplantation in concert with indications of incipient bone marrow recovery.

Fluid balance should be optimized, although the patient is not manifesting evidence of fluid overload. Corticosteroids are sometimes used to treat presumed alveolar hemorrhage, although their benefit in this setting has not been established. Bronchoscopy might reveal evidence of hemosiderin-laden macrophages to suggest the diagnosis of alveolar hemorrhage, but the finding is nonspecific. Bronchoscopy might help identify infectious or malignant causes, but most clinicians would prefer to intubate such a patient before contemplating bronchoscopy. Intubation is potentially very hazardous in a patient at such high risk of bleeding or developing superinfections. The best early strategy is to initiate noninvasive positive-pressure ventilation, which, while still yielding a high mortality rate, reduced mortality compared to conventional oxygen therapy and intubation (if indicated) in a randomized controlled trial on a similar group of patients. Bronchoscopy can be performed during noninvasive ventilation if needed.

Key Point

  • In selected immunosuppressed patients with respiratory failure, noninvasive positive-pressure ventilation is associated with a lower mortality rate than conventional oxygen therapy and intubation.