Utilization of alteplase in trauma victim with an open abdomen

Abstract

Trauma victims with multisystem injuries are at risk for the development of deep vein thrombosis and pulmonary embolus (PE). The use of thrombolytic therapy remains very controversial and not well-documented in both the postsurgical and trauma subset of patients. Major trauma, surgery or head injury have been noted as absolute contraindications to thrombolysis in acute myocardial infarction. The decision to utilize thrombolytic therapy cannot be algorithmic; it must be based on the assessment findings for each individual patient. The risk to benefit ratio should be the major consideration to ensure the best possible outcome is granted. Treating injured patients experiencing high-risk PE causing an immediate threat to life may necessitate forming a comparative view of the adverse events associated with thrombolytic medications.

INTRODUCTION

Thrombolytic drugs have intrigued researchers and medical professionals for over seven decades. Since the late 1960s, much research has centered on the use of thrombolytic therapy in patients presenting with pulmonary embolism. Due to the fibrinolytic properties of this class of drugs, many studies have been undertaken to assess the risk to benefit ratio of this treatment option. Because the major complication of thrombolytic therapy is bleeding, many studies over the years have excluded patients with conditions that predisposed them to possible hemorrhage such as significant head trauma, previous intracranial hemorrhage, recent surgery, internal bleeding or major trauma. These exclusions have opened an avenue for case studies, like the one that follows, to demonstrate the success of selectively utilizing thrombolytics as a life-saving treatment in a postoperative, multisystem trauma patient experiencing a high risk pulmonary embolus (HRPE).

CASE REPORT

A 25-year-old male was involved in a motor vehicle crash (MVC) in which his vehicle went over the side of an elevated bridge and caused occupant ejection upon impact. Upon Emergency Medical Service arrival, the preliminary physical assessment revealed the following: Patent airway, labored respirations, decreased level of consciousness with a glascow coma score (GCS) of 6, hypotension and extreme tachycardia. Secondary assessment exposed facial trauma with crepitus, an open clavicle fracture, abdominal distention, multiple lacerations, and hypothermia.

Immediately after arrival to the trauma center, the patient was intubated and underwent bilateral thoracostomies for relief of hemo/pneumothoracies. The initial laboratory findings included low hemoglobin and hematocrit levels, profound acidosis (7.15 pH) and a high base deficit (–12.9). Secondary to his state of shock, the massive transfusion protocol was initiated and a diagnostic peritoneal lavage (DPL) was performed. The patient was taken immediately to the surgical suite after the DPL returned 10 ml of frank blood.

Approximately 2 L of blood were noted in the abdomen upon opening for an exploratory laparotomy. A ruptured spleen and pancreatic laceration were determined to be the sources of active bleeding. A splenectomy and pancreatic repair ensued. The patient had received 14 units of packed red blood cells (PRBC) and multiple units of fresh frozen plasma (FFP). Secondary to the massive amounts of volume replacement required, the bowel was becoming edematous requiring the trauma surgeons to pack the abdomen open. The patient was transferred to the intensive care unit (ICU) immediately after completion of the surgical procedure, where his blood pressure remained labile despite the use of vasopressor medications.

Early on postinjury day four, a clinical diagnosis of PE was made based on the patient's continued respiratory instability, significant ventilatory demands, hypoxia, tachycardia and hypotension refractory to volume and pressor support. A venous Doppler study revealed the presence of ecogenic material to both lower extremities despite the continuous use of graduated elastic stockings and sequential compression devices. The patient underwent emergent placement of a vena caval filter in the ICU. His respiratory status continued to decline, leaving the patient too unstable for transport to radiology to undergo a computed axial tomography (CT) scan for diagnostic confirmation of PE. A bedside echocardiogram was performed delivering inconclusive results; poor visualization of ventricular and valvular dimensions and function were incurred secondary to the chest and abdominal bandaging and packing. The patient later suffered cardiopulmonary arrest, for which cardio-pulmonary resuscitation (CPR) and advanced cardiac life support (ACLS) measures were immediately initiated. Based on clinical symptoms with a presumptive diagnosis of massive pulmonary embolism, the decision was made to administer thrombolytic medication in combination with the other resuscitative measures. An Alteplase 15 mg bolus was administered via right subclavian central line followed by a continuous 85 mg infusion over 2 hours. Approximately 35 minutes after initiation of Alteplase, the return of spontaneous circulation was noted.

Close observation for bleeding complications was maintained. Notable early findings included an increase in serosanguinus fluid output from the abdominal drains, an increase in bloody drainage from the right chest tube, and blood-tinged urine. The patient received blood transfusions as a result of declining hemoglobin and hematocrit levels two consecutive days following thrombolysis. A delayed complication attributed to thrombolytic therapy was noted during week 6 when the patient again demonstrated marked respiratory decline requiring video-assisted thoracoscopic surgery (VATS) and subsequent open thoracotomy to evacuate the pleural space of multiple large blood clots and debris.

DISCUSSION

Venous thrombus formation occurs in approximately 50% of all trauma victims.[¹] The incidence of PE after trauma varies from 0.1% to 1.6% in recent studies.[²] Even though the incidence of fatal PE is relatively low (0.45%-4.2%) after major trauma, HRPE with symptoms of right ventricular failure such as hypoxia, hypotension, tachycardia, cyanosis, dizziness/syncope and circulatory collapse is either responsible for or a contributory factor in greater than 10% of all trauma deaths not caused by the initial injuries.[¹³]

Multiple dynamics in trauma patients make treatment decisions complex. Sustained injuries and/or increased bleeding risk often require delays in the initiation of deep vein thrombosis (DVT) prophylaxis. The pathophysiology associated with multisystem trauma frequently establishes a hypercoagulable state which is most rampant in the first 72-96 hours postinjury.[⁴⁵] Treatments and procedures which are essential to the patients’ recovery such as major surgical procedures, especially those involving the chest or abdomen with prolonged anesthesia administration, immobilization of a body part, and restricted mobility increase bias towards the development of thrombi.

DVT and subsequent PE continue to occur despite the use of preventative measures such as vena caval filters, heparin medications, elastic stockings, and sequential compression devices. Multiple studies have been published on the different methods and combination of methods utilized for DVT/PE prophylaxis and their resultant patient outcomes.[^6–10] One constant across all these studies is the absence of 100% prevention of clot formation regardless of the treatment option/s chosen. With the inevitability of thrombus formation, practitioners should have a high index of suspicion for the development of PE especially in patients predisposed to hypercoagulable states.

Because the presentation of PE is varied, based on the clot burden and the site of lodgment in the pulmonary vasculature, diagnosis is challenging due to the lack of specificity in the presenting signs and symptoms. Trauma patients further confound the diagnostic process with presentations of injuries and disease processes which can provide sufficient rationale to attribute the noted symptoms to conditions or factors other than PE. Modalities such as CT scan, echocardiogram and pulmonary angiography may be utilized to aid the diagnostic process. Patient condition and facility resources often dictate the diagnostic tools employed. As presented in this case study, available diagnostic methods may be inadequate to confirm or exclude PE. In such instances diagnosis and treatment must be based solely on clinical assessment findings.

Treatment options for HRPE include thrombolysis, surgical pulmonary embolectomy, and percutaneous catheter-based thrombus fragmentation and aspiration.[¹¹] According to the current guidelines for the management of HRPE, thrombolysis is the first line treatment unless an absolute contraindication exists.[¹¹] While the alternative options of surgical embolectomy and thrombus fragmentation-aspiration are viable and have been proven effective, they remain second-line choices. This may be related to the fact that both are invasive and require equipment and personnel unavailable to many institutions. In comparison, thrombolytic medications are relatively inexpensive, available in most hospitals, and do not require advanced technology or invasive procedures for administration.

Historically, the major concern with the administration of thrombolytic medications has been the occurrence of major bleeding events. Recent large studies have shown a decrease in the incidence of severe bleeding complications (13%) and occurrence of intracranial or fatal hemorrhage (1.8%),[^11–14] whereas registry data suggest rates of 21.9% and 3%, respectively.[¹⁵] Regardless of which studies are viewed, thrombolytic-induced fatality rates pale when compared with mortality rates of patients experiencing HRPE with symptoms of hypotension, low cardiac output and shock (30%-50%) and those who suffer a HRPE-induced cardiac arrest (70%).[¹⁵¹⁶] In performing a risk/benefit ratio clinicians need to bear in mind the very poor prognosis of patients experiencing HRPE. This evaluation can lead to a divergence in the criteria for determining absolute thrombolytic contraindications during the treatment of life-threatening HRPE as opposed to acute myocardial infarction (AMI). Absolute contraindications for AMI (with the exception of known intracranial pathology) may be considered relative when weighing treatment options for a deteriorating patient with HRPE.[¹¹¹⁷¹⁸]

CONCLUSIONS

Postoperative, multisystem trauma patients pose a complex challenge in the prevention, diagnosis and treatment of PE. The severity of the symptoms often dictates the most appropriate treatment regime. While thrombolytics are not recommended for all levels of PE, they should be a consideration in trauma patients suffering life-threatening HRPE. The risks of major bleeding complications and intracranial/fatal hemorrhage linked to thrombolytic therapy are diminutive when compared to the poor prognosis and high mortality rate associated with inadequately treated HRPE and therefore should not be the decisional focal point in an extreme situation.