Air Care Series: A Case of Massive Clot
/History of Present Illness:
Air Care was dispatched for an inter-facility transfer of a female in her 80s who initially presented with shortness of breath and was found to have a saddle pulmonary embolism. Prior to Air Care’s arrival, the patient developed acute hypoxic respiratory failure requiring endotracheal intubation. Following intubation, the patient experienced two distinct episodes of hypoxia leading to pulseless electrical activity (PEA) arrests. Standard ACLS was performed and atropine was administered during the initial PEA arrest leading to return of spontaneous circulation (ROSC). During the second PEA arrest, epinephrine was administered with immediate ROSC. Following the second arrest, 100mg of tPA was administered.
Vitals: HR 30 - RR 24 - BP 92/50 - O2 Sat 82%
Ventilator Mode: Volume Control (Assist Control) - Tidal Volume: 400mL - PEEP: 14 - FiO2: 100%
Physical Exam
The patient was an elderly female who was intubated and unresponsive. The patient was bradycardic with no murmurs, rubs, or gallops. The patient was unresponsive and comatose with no motor movement to painful stimulus. Her skin and abdominal exams were within normal limits.
Pre-Hospital Course
Given the patient’s presentation to a hospital without intensive care capabilities, this patient required critical care transportation to a higher level of care. When the medical crew arrived, the patient remained bradycardic and hypoxic, and shortly thereafter experienced a third PEA arrest. CPR was initiated and 1 mg of epinephrine was administered. Following two minutes of CPR, ROSC was achieved. Post-ROSC, an amp of calcium chloride was administered. The patient’s initial ventilator setting of positive end expiratory pressure (PEEP) was decreased to 10cm H2O to decrease the intrathoracic pressure and improve the patient’s preload.
After exchanging the outside hospital ventilator for Air Care’s transport ventilator, the patient’s respirations became dyssynchronous and she was sedated with ketamine. Although dyssynchronous, the patient did not exhibit bradycardia at that point and had oxygen saturations between 80-88%. Given the patient’s critical condition, the medical crew elected to load the patient in the aircraft and continue to optimize ventilator settings throughout transport.
En route, the ventilator was changed from volume control to pressure control with a PEEP of 8. The patient became more synchronous with the ventilator and maintained stable oxygen saturations while having significant improvement in mean arterial pressure from 67mmHg to 96mmHg. Upon arrival to the receiving hospital, the patient remained stable, though critically ill, and was transported to the hospital’s cardiovascular intensive care unit (CVICU).
Hospital Course
Ultimately the patient was extubated to nasal cannula and subsequently maintained her oxygen saturations. Following extubation, the patient was neurologically intact. The patient was determined not to be a thrombectomy candidate due to her thrombolysis. Four hours post-extubation, the patient experienced confusion and difficulty moving her left upper and lower extremities which was unfortunately a sizeable intraparenchymal hemorrhage.
Discussion
The incidence of pulmonary embolism is approximately 60-70 per 100,000 people with a mortality rate of approximately 30% when left untreated and 8% when treated appropriately. [1] While significant data exists regarding thrombolytics in patients with pulmonary embolism, there is limited research on the medical optimization of these patients prior to therapy. This discussion serves to describe the pathophysiology of hemodynamic decompensation in the setting of pulmonary embolism and optimal medical management of these challenging patients.
Pathophysiology
The pathophysiology of a massive pulmonary embolism is directly related to right ventricular function. For a patient with no previous cardiopulmonary disease, the right ventricle will function normally until approximately 25-30% of the pulmonary vasculature is obstructed by thrombus. Once this threshold is reached, pulmonary arterial pressure begins to rise from the normal value of 8-20 mmHg due to physiologic vasoconstriction of the pulmonary vasculature in response to hypoxia. Patients will then begin to experience signs and symptoms of pulmonary embolism such as dyspnea, tachycardia, and pleuritic chest pain. [2] As clot burden approaches 50-75% of the pulmonary vasculature and pulmonary arterial pressures start to eclipse 40 mmHg, the right ventricle begins to dilate and right ventricular stroke volume decreases abruptly. This is because right ventricular stroke volume is more sensitive to after-load when compared to the left ventricle (Fig. 1). [3]
Right ventricular wall stress (pressure x radius) is inversely proportional to right ventricular oxygen uptake. Therefore during acute pulmonary embolism, the right ventricle slowly starts to become ischemic. Right ventricular dilation additionally leads to decreased cardiac output. Cardiac output is reduced due to both decreased stroke volume and septal shift into the left ventricle. Right ventricular septal shift decreases left ventricular distensibility and ultimately left ventricular end-diastolic volume, further lowering the overall cardiac output. [3] All of these changes lead to profound obstructive and cardiogenic shock. This cycle, colloquially known as the “death spiral of pulmonary embolism,” can be prevented with prompt diagnosis and optimal hemodynamic management.
Volume Resuscitation
The primary treatment for pulmonary embolism is to reduce clot burden and pulmonary vascular resistance via anti-coagulation and/or thrombolytics. Providers can assist the patient who continues to decompensate despite appropriate treatment by optimizing the patient’s preload. In the setting of right ventricular dilation, providers must be judicious in the amount of fluid administered. A prior study done by Mercat et al. (1999) demonstrated that a 500 mL bolus given over 20 minutes had a variable effect on hemodynamics in those with acute massive pulmonary embolism. This variable effect is likely based on the patient’s initial right ventricular end-diastolic volume (RVEDV). 5,6,7 Unfortunately, prehospital providers cannot measure RVEDV directly and must instead administer fluid based on hemodynamic response. In patients with dilated right ventricles, cardiac output decreases with additional fluid administration (Fig. 2). If fluid is continuously administered to the already dilated RV, the septum is shifted further into the left ventricle and accelerates the vicious cycle described previously, resulting in worsening shock. Although volume may provide benefit in those are that are initially hypovolemic, clinicians should only administer small volume boluses and quickly abandon further volume resuscitation and move to pressor support if no measurable response is made to fluid administration.
Avoiding Intubation
Patients with pulmonary embolism develop tachypnea and hypoxia, prompting providers to consider intubation. In the setting of tenuous hemodynamics due to right ventricular failure, intubation can lead to acute decompensation and cardiac arrest. If intubation must be performed, it is important to consider the downstream effects and prevent post-intubation decompensation. When performing rapid sequence intubation, providers must remain vigilant when selecting induction agents. Patients in shock have a very high intrinsic sympathetic tone, and induction agents often cause hypotension when this tone is lost. Once the patient is intubated and receives positive pressure ventilation, he or she will experience an immediate reduction in right ventricular preload due to increased intrathoracic pressure. Providers should be aware of this phenomenon and put ventilated patients on the minimal amount of PEEP that allows adequate oxygenation. Providers also must be aware of the effect of tidal volume and respiratory rate on pulmonary vascular resistance. An appropriate tidal volume must be selected to minimize both the resistance of extra-alveolar vessels and intra-alveolar vessels. [8] Providers should strive to achieve lower tidal volumes (6 mL/kg of ideal body weight) to minimize pulmonary vascular resistance. [6] Decreased arterial blood pH leads to increased pulmonary vascular resistance as well, so providers should set an appropriate respiratory rate once ventilated to minimize additional respiratory acidosis. [8]
Vasopressor Support
There is only a finite amount of fluid that can be given before a patient starts to have worsening right ventricular dilation and decreased cardiac output. If judicious volume resuscitation alone does not improve the patient’s hemodynamics, vasopressors should be used to support the patient’s blood pressure. Canine models in prior studies have shown that norepinephrine increases mean arterial pressure and cardiac output more than phenylephrine. [9] Numerous studies have compared norepinephrine and epinephrine, and the data does not support one vasopressor over the other. Recent canine studies have shown that norepinephrine increased cardiac output and myocardial blood flow when compared to epinephrine analogs. [7,9,10] Either norepinephrine or epinephrine can be used as the first line vasopressor and depending on the patient’s hemodynamic response, both can be used. If the patient’s mean arterial pressure does not respond to norepinephrine or epinephrine, vasopressin can also be added. Vasopressin only increases systemic vascular resistance and has no effect on pulmonary vascular resistance. This makes vasopressin especially efficacious in the treatment of obstructive shock from pulmonary embolism. [11] In the event that further support is required, there is weak evidence for the use of low dose dobutamine (5 μg/kg/min). Dobutamine causes increased cardiac output via positive inotropy, while slightly lowering pulmonary and systemic vascular resistance. [12,13] Other positive inotropes, such as milrinone, can be used with the caveat that the hemodynamic effects will be delayed compared to dobutamine.
Nitric Oxide, Epoprostenol
There is growing evidence supporting nitric oxide and epoprostenol use in pulmonary embolism. [14,15] Pulmonary vasoconstriction is not only due to clot burden, but also from humoral factors released from platelets. These factors include vasoactive and thrombin producing peptides that cause pulmonary vasoconstriction. [3] Through the action of guanylate cyclase, nitric oxide stimulates the production of cyclic guanosine monophosphate (cGMP) which reduces calcium release from smooth muscle cells in the pulmonary vasculature. [16] Epoprostenol activates endothelial prostacyclin receptors which causes vascular smooth muscle relaxation and vasodilation. Both of these medications cause pulmonary vasodilation and decrease right ventricular afterload. Nitric oxide should be used as a salvage therapy to lower pulmonary vascular resistance in patients who are acutely decompensating despite thrombolytic and vasopressor administration. Initial starting doses begin at 5 parts per million and can be increased to 40 parts per million, similar to doses given in pulmonary hypertension. In the setting of air transportation, a respiratory therapist is needed during transport to administer the nitric oxide. Nitric oxide is a limited resource, especially in the community setting, and providers should only turn to this therapy if the patient has refractory hemodynamic collapse. It is important to note that nitric oxide is no longer available at many institutions due to cost and intense resource utilization, and many have adopted epoprostenol as the first line inhaled pulmonary vasodilator. If providers have attempted all of the above measures and the patient continues to have refractory shock, ECMO is the final treatment option. Patients can be cannulated prior to transport or upon arrival at the receiving facility. Venous-arterial ECMO is the modality of choice to completely bypass the pulmonary and cardiovascular systems while ongoing anticoagulation to promote clot dissolution is continued.
Conclusion
Pulmonary embolism can lead to rapid hemodynamic collapse even in the post-thrombolytic setting. The pathophysiology of the acutely decompensated patient with a pulmonary embolism is directly related to the function of the right ventricle. Fluid resuscitation should be judicious as a large volumes can lead to worsening right ventricular dilation and worsening cardiac output. Vasopressors have been shown to be effective in maintaining mean arterial pressure in these patients, specifically norepinephrine and epinephrine. Intubation should only be performed if absolutely necessary as induction and positive pressure ventilation can lead to a rapid drop in preload and subsequent cardiac arrest. The “death spiral of pulmonary embolism” can be prevented with prompt diagnosis and optimal management of the patient’s hemodynamics.
