Pulmonary embolism: An Unusual Cause Of Acute Liver Failure
M Vizcaychipi, C Burt, R Burnstein
coagulopathy, liver failure, pulmonary embolism, right heart failure
M Vizcaychipi, C Burt, R Burnstein. Pulmonary embolism: An Unusual Cause Of Acute Liver Failure. The Internet Journal of Emergency and Intensive Care Medicine. 2006 Volume 10 Number 2.
Pulmonary embolism is still a challenging diagnosis and a very high index of suspicion is required. Symptoms and signs of acute right heart failure are still non-specific and often vary according to the precipitating condition. In this particular case, evolving liver failure and severe coagulation disorder as the initial presentation made the management of this patient very challenging and several causes of sudden decompensated liver failure were ruled out. Acute reduction of splanchnic flow was considered but in the context of relative good oxygenation and no history or clinical signs of deep venous thrombosis, the diagnosis of pulmonary embolism was not considered as a primary cause of liver failure and evolving multiple organ failure. Complementary studies, namely echocardiogram and use of a pulmonary artery catheter immediately raised the suspicion of a saddle pulmonary embolus. In view of the findings, an emergency contrast-enhanced spiral computed tomography was performed and the diagnosis of pulmonary embolism was made.
A 64 year old gentleman was admitted to hospital because of increasing shortness of breath and peripheral cyanosis.
The patient had complained of dizziness, shortness of breath and had become anorectic and nauseated two days before admission. The next day he visited his GP who suggested increasing his fluid intake. The following morning he rang the emergency service because of progressive shortness of breath.
The patient had stopped working a few weeks previously in view of several spells of palpitations. He had a history of depression, emphysema, hypertension and an event of angina many years earlier. He had also had a right inguinal hernia repaired in 1994.
Three months before admission a 24-hour Holter monitor showed paroxysmal supraventricular tachycardia with frequent atrial and ventricular ectopics.
One month before admission, a chest radiograph revealed an enlarged heart and hyperinflated lungs. A transthoracic echocardiogram showed mild tricuspid regurgitation.
Fifteen days before his admission a liver ultrasound detected a congested liver with a moderate amount of ascites. It also showed a distended gallbladder and thickened wall. Blood results were unremarkable.
The patient was sedentary because of palpitations and was allergic to penicillin. He had occasionally consumed alcohol and had stopped using tobacco 15 years before admission.
On examination, the patient appeared ill and slightly confused. The jugular veins were not visible. Breath sounds were diminished over both lungs, with crackles at both lung bases. The heart sounds were normal. An abdominal examination revealed a soft abdomen, present bowel sounds and no organomegaly. There was symmetrical pedal oedema without evidence of deep venous thrombosis. His temperature was 35.3°C, pulse was irregular at 155 beats per minute, and he had a respiratory rate of 30 breaths per minute and saturations of 84% on room air. The initial blood pressure was non recordable.
Initial Blood results showed:
Arterial blood gas revealed pH 7.37, PCO2 5.89 kPa, PaO2 14.79 kPa on FiO2 28%, BE -0.3 mmol/l, HCO3 25.2 mmol/l (See table 1), Na 121 mmol/L, K 4.96 mmol/L, lactate 4.2 mmol/L. Other results of interest were glucose 1.4 mmol/L, urea 24.5 mmol/L, creatinine 205 umol/L, total bilirrubin 189uml/L, ALT 1397 U/L, Platelets 50*10/l, PT 42.6 Seconds, KPTT 56.8 Seconds, Fibrinogen 0.6 g/l D-Dimer more than 4000 ng/mg and troponin I 0.28.
The results of other laboratory tests are showed in table 2.
In view of preliminary findings the initial interpretation was liver dysfunction and disseminated intravascular coagulopathy accompanied with some degree of relative adrenal insufficiency in the context of severe sepsis and treatment was started accordingly.
Fluid resuscitation, ceftriaxone 2g, dexamethasone 8mg, dextrose 50% were administrated in the A&E department. After a long discussion with the haematologist, blood products were administrated to correct his coagulopathy.
In view of evolving organ dysfunctions the patient was electively intubated and ventilated, central and arterial access were gained and inotropic support commenced to maintain a systolic blood pressure above 90 mmHg. Once blood pressure was stable the patient was transferred to the neurocritical care unit for general intensive care management.
Critical care management
On arrival to the critical care unit the patient showed profound peripheral cyanosis, progressive metabolic acidosis (pH 7.13, PCO2 8.2, PO2 35.1, BE -9.3, HCO3 18.9 on 60% of FiO2) and remained anuric in spite of aggressive fluid resuscitation and inotropic therapy.
The above findings prompted us to continue aggressive fluid resuscitation with colloids, start an infusion of N-acetylcysteine and we also inserted a pulmonary artery catheter (PAC) to guide our treatment.
The first PAC reading showed a CVP of 35 mmHg and some difficulty to float the catheter beyond tricuspid valve was experienced. A transthoracic echocardiogram was performed immediately showing massive dilatation of the right ventricle and atrium with severe tricuspid regurgitation and a paradoxical septum. Very poor left ventricular function was also noticed.
Systolic blood pressure remained around 75 mmHg despite a considerable dose of vasopressors and inotropes.
Sudden extreme bradycardia with lost of cardiac output prompted further cardiopulmonary resuscitation, regaining cardiac output 20 minutes later and subsequently becoming hypertensive. A reduction of noradrenaline and adrenaline doses to less than 0.1 mcg/kg/min was then required.
Further improvement of the blood pressure was noted with manipulation of the PAC, therefore possible saddle embolus was considered. Agitating the PAC and balloon guided by echocardiogram plus transducer waveforms caused a dramatic improvement in echocardiogram appearance. There was no shunt from right to left on bubble conducted study but a clear reduction in pulmonary pressures was seen (from 65mmHg systolic pulmonary pressure to 35 mmHg.)
In view of relative haemodynamic stability the patient was transferred to CT scan for CTPA that confirmed pulmonary embolism involving the right lobar arteries.
Anticoagulation with heparin was started as per haematological advice.
Despite fluid resuscitation and an adequate mean arterial pressure the patient remained anuric and acidotic, hence continuous venous-venous haemofiltration was commenced.
A six hour period of stability was achieved but, unfortunately a second cardiac arrest occurred without response to cardiopulmonary resuscitation. The patient was pronounced dead 45 minutes later.
The key features of this case are acute liver failure, coagulopathy and renal dysfunction of sudden onset evolving in hours to multiple organ failure and death.
The main question in this particular case is “what causes of liver failure can lead to a severe degree of multiple organ failure over a period of less than 12 hours?” See table 3.
There was no history of drug overdose, infection or systemic disease. However there were some subtle signs of chronic right cardiac failure which, in addition to sedentary life may have led to a pro-thrombotic state hence compromising the circulation with a further reduction in blood flow and delivery of oxygen to the splanchnic circulation.
Furthermore, this hypercoagulopathic state may be expressed with a low platelet count and prolonged thrombin time in the presence of liver dysfunction. These combined may generate misinterpretation of the clotting profile leading to correction of a presumptive disseminated intravascular coagulopathy; management that of course will aggravate the unresolved primary problem.
Correction of clotting abnormalities without clinical evidence of active bleeding and no need for invasive procedures, is difficult to justify in view of the fact that DIC has two components and it is very difficult to ascertain whether the patient is suffering from thrombosis or internal bleeding. To this end clinical judgment and the patient's history will dictate if correction of coagulopathy is necessary.
In line with our discussion of multiple organ failure, we should highlight that this may occur secondary to a sudden reduction of cardiac output with profound mesenteric hypoperfusion. Thus, all systems can fail. Whether this occurs in a simultaneous or sequential (domino) fashion is determined more by the state and severity of the primary insult and the complications that develop.
It is also clear now that severe inflammation itself associated with tissue necrosis or other problems can produce or activate mediators that depress the circulation and alter organ function. These descriptions of clinical factors by Goris et al (1) indicate clearly that infection is not necessary. It is also apparent that persons with limitations of function of one or more organs are more susceptible to develop this problem than are otherwise normal persons.
This is especially true in patients with vascular occlusive disease, chronic obstructive lung disease, and hepatic damage, immunosuppression from various disease processes or organ transplantation, and cardiac disease.
The common thread underlying all of these problems seems to be an altered circulation, reduced blood flow, inadequate tissue perfusion, and ischaemia. The recognition that patients developing multiple organ failure often developed what to appear to be a septic state, but without bacterial infection led to the description of the nonbacterial septic clinical state by Meakins & Marshall(2)
Acute reduction of cardiac output may be secondary to a sudden thrombo-embolic event leading to multiple organ dysfunctions. Initial clinical presentation may be florid and clinical diagnosis may be challenging and difficult to ascertain.
Decompensated right ventricular failure may develop acutely, as in pulmonary embolism which leads to a sudden increase in right ventricular pressure causing overload.
In pulmonary embolism, the extent of pulmonary obstruction appears to be a crucial factor in predicting the degree of right ventricular dysfunction. The sudden increase in the RV afterload increases wall tension and lead to chamber dilatation and impaired diastolic and systolic function. The interventricular septum paradoxically shifts towards the left ventricle and leads to impaired filling of this chamber under the constraint of a noncompliant pericardium.
Acute tricuspid regurgitation resulting from RV dilatation and systolic dysfunction also leads to a diminished right-sided cardiac output and a reduction in the left ventricle preload. Increases in RV wall tension along with decreases in systemic cardiac output and perfusion pressures may alter the equilibrium between the myocardial oxygen supply and demand, leading to ischaemia and possible infarction (3).
As the right ventricle loses its pumping function, blood may back up into other areas of the body, producing congestion. Congestion affects the liver, the gastrointestinal tract, and the limbs. In addition, the right ventricle may be unable to pump blood efficiently to the lungs and to the left ventricle.
Symptoms that may lead to early diagnosis are shortness of breath, swelling of feet and ankles, pronounced jugular veins, palpitations, fatigue, weakness, faintness. Clinical signs of acute right ventricle failure are hypotension, tachycardia, tachypnoea, cyanosis, tricuspid regurgitation and an accentuated sound of pulmonary valve closure.
However, symptoms and signs of right ventricle failure are still non-specific and often vary according to the precipitating condition.
Patients with conditions leading to increased RV afterload may report dyspnoea, light-headedness, and syncope. In both right ventricular infarction and pulmonary embolism, chest discomfort may be an important presenting symptom. Patients with acute-on-chronic right ventricular failure may report right-quadrant discomfort from hepatic congestion, as well as lower extremity swelling.
Management of pulmonary embolism is clearly understood and guidelines are very easy to follow. In our patient anticoagulation was started as soon as the diagnosis was made and we considered the role of thrombolysis or mechanical thrombectomy. The role of thrombolysis in patients who suffer pulmonary embolism with cardiovascular embarrassment is clear, but we were not entirely certain about this modality of treatment in the context of severe coagulopathy and in view of the lack of evidence to support this treatment we decided against it. Regarding mechanical thrombectomy, this was not an option because of the lack of this resource in our centre and instability of the patient precluded transfer to a cardiac centre.
Pulmonary hypertension, increased pulmonary vascular resistance and reduced cardiac output have been reported in primary lactic acidosis (4)
We have also found only a few cases of massive pulmonary embolism presenting as disseminated intravascular coagulation (5, 6)
Furthermore, we could not find in the literature a case of pulmonary embolism presenting as severe multiple organ dysfunctions with predominantly signs of liver and haematological dysfunction and relatively normal oxygenation and ventilatory parameters.
Post mortem examination
Cardiovascular system: Significant atherosclerosis and stenosis within the distal segment of the left anterior descending coronary artery, mild hypertrophy of the left ventricle and an attached thrombus within the left atrial appendage.
Respiratory system: Pulmonary embolus within the right lower lobe.
Gastro-intestinal system: The liver was mottled nutmeg appearance on the cut surface. There was no thrombus within the hepatic artery or the portal vein
There was an established colonic infarction within the caecum as well as ascending and proximal part of transverse colon as well as the distal 70 to 80 cm of the small bowel.
Hence, the causes of death are the following:
1a. Small bowel and colonic infarction
2. Left atrial appendage thrombosis, pulmonary embolism and liver failure.
This gentleman had presented with evolving acute liver dysfunction, disseminated intravascular coagulation, and acute adrenal insufficiency in the context of sudden right-sided heart failure secondary to massive pulmonary embolism.
In spite of every medical effort to fully support declining organ functions and treat primary cause of his acute illness this gentleman died
Lesson to learn
Pulmonary embolism is still a challenging diagnosis and very high index of suspicion is required
Disseminated intravascular coagulation may present with signs of thrombosis and lack of signs of active bleeding may need to refrain us to correct blood abnormalities until the primary diagnosis is ascertain
Acute right-sided heart failure must prompt us to diagnose pulmonary embolism until proving an alternative diagnosis
Thrombolysis needs to be considered in patient in shock with proven pulmonary embolism.
We would like to thank you Dr Glyn Thomas, cardiology registrar who kindly performed the echocardiogram.