Transplant Emergencies Part II: Organ Specific Complications

Authors: Brit Long, MD (@long_brit, EM Physician at SAUSHEC, USAF) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) // Edited by: Jamie Santistevan, MD (@Jamie_Rae_EMdoc, Admin and Quality Fellow at UW Madison, WI)

Cases

A 33-year-old female presents with shortness of breath and lower extremity swelling. She has a history of heart transplant two years ago and is currently on immunosuppressive treatment. Her HR is 110, which according to the patient, is normal. What do you need to consider? What are keys in the evaluation and management of this patient?

 A 42-year-old male presents two months after liver transplant with fever, RUQ pain, and ascites. He is tachycardic and febrile on initial examination with RUQ tenderness to palpation. He appears systemically ill. What conditions need to be on your differential?

 This is part II of a series detailing transplant emergencies. Part I covered transplant infection, rejection and medication side effects. We will evaluate renal, cardiac, liver, and lung transplant complications in this post.

Renal Transplant

Kidneys are the most commonly transplanted organ in the U.S., and grafts are obtained from living or deceased donors.1-3 The renal graft is often placed in the recipient’s pelvis.3,4 Key connections include the renal artery to the external iliac artery, the renal vein to the external iliac vein and the ureter to the bladder.3,4 Several complications may arise with the transplant, with the most common being urinary tract infection anywhere along the tract. Leukocyte presence in the urine may occur with rejection or infection.3,5-7 If UTI is diagnosed, at least two antibiotics should be utilized upon admission.3,5

Anatomic Complications

These include vascular thrombosis and stenosis.3,8,9 Arterial stenosis occurs in up to 10% of cases any time after transplant. Patients present with uncontrolled hypertension, decreased urine output, and peripheral edema. Doppler ultrasound (US) may demonstrate flow limitation, but diagnosis requires angiography. Treatment includes stent placement by vascular surgery and/or interventional radiology. Renal artery thrombosis most commonly occurs in the immediate postoperative period, with sudden decrease in urine production. Venous thrombosis occurs in 4% of cases, and this more commonly presents with pain and erythema over the graft site, decreased urine output, abdominal pain, and nausea/vomiting. Diagnosis requires CT angiography, though US may suggest the diagnosis. 3,8-10 Treatment includes thrombolysis. Nephrectomy and graft replacement are often required.9

Hematoma and Hematuria

Peri-transplant hematoma occurs in 2% to 3% of patients.3,4,10 Severe acute rejection may also cause swelling and rupture of the transplant.10 A hematoma presents with pain over the graft site, decreased H/H, and increased serum Cr. US can suggest the diagnosis, but CT of the abdomen/pelvis best characterizes the hematoma.11 Surgical repair or graft replacement is usually needed. Bleeding can be seen after allograft biopsy, which presents with gross hematuria. If obstruction occurs, bladder irrigation with triple lumen catheter may relieve the obstruction. However, severe hematuria may require transfusion of blood products with angiographic intervention.3,4

Ureteral Obstruction

Ureteral obstruction occurs in 3% to 6% of transplants.3,4,12 Patients with early obstruction present with decreased urine output due to clot, edema, or stricture involving the ureter or anastomosis. 3,4,12 Ultrasound may show hydronephrosis of the transplanted kidney. A Foley catheter is required, and if the condition does not resolve, surgical revision with stent is needed. Urinary leakage may occur at any level of the urinary tract, with a rate of 2% to 5% within the first few months after transplant.4,8,13 This should be considered when a patient develops fluid leakage from the surgical site, abdominal pain, and perineal swelling. Bedside US will reveal a peritransplant fluid collection. Fluid collection will demonstrate elevated urea nitrogen and creatinine, similar to the serum concentrations. Foley catheter placement, followed by urology consultation for definitive management, is needed. 4,8,13

Lymphocele

Lymphocele results from lymphatic vessel leakage, forming a collection of lymphatic fluid most commonly between the lower pole of the transplant and the bladder. This occurs in 5% to 15% of patients, often within the first three months.4,8,14 Small hydroceles are usually asymptomatic, though larger fluid collections will present with swelling and pain over the graft. Bedside US can suggest the diagnosis with fluid collection, with CT providing definitive diagnosis.4,13,14 Urology and transplant surgery should be consulted for fluid aspiration.4,8,13,14

Liver Transplant

Liver transplants are commonly associated with complications. The most common conditions emergency providers will manage are mechanical complications, often with abdominal pain, nausea/vomiting, early satiety, and ascites.15-19

Vascular Complications

Vascular disorders can affect the hepatic artery or portal vein. Thrombosis of the hepatic artery affects 4-12% of patients, due to rejection, artery kinking, or technical anastomotic failure.15,16 Doppler US possesses a sensitivity of 90% for thrombosis.17 Mortality reaches 80% if untreated, which requires immediate transplant and vascular surgery consultation. Patients usually require a new transplant. Artery stenosis occurs in up to 14% of patients due to vascular injury during the surgery. Stenosis presents similarly to thrombosis, and Doppler US is not as reliable with a sensitivity of 70%.18 Diagnostic angiography may be required.15-18 Treatment includes rapid consultation with vascular and transplant physicians, often with transplant reconstruction. Pseudoaneurysms can be extrahepatic, paraportal, or intrahepatic, with presentation depending on location. Intrahepatic pseudoaneurysm may cause hemobilia, hemoperitoneum, or GI bleeding.15-17 Pseudoaneurysms appear hypoechoic on US, and CT often demonstrates a focal lesion with central enhancing contrast. Many of these lesions can be treated with embolization.15-19

Biliary Complications

Biliary conditions are major complications after liver transplant and occur in 4% to 25% of patients.20-23 These consist of strictures, leaks, biliary stones, and fluid collection, divided into early (within 4 weeks) and late.20-23 Patients commonly present with abdominal pain, specifically right upper quadrant, and they may have jaundice and fever. 21-24 LFTs including alkaline phosphatase and bilirubin are elevated.21-24 US with Doppler has a sensitivity of 38% to 66%.23,24 If US is unrevealing, cholangiogram may be required, though magnetic resonance cholangiopancreatography (MRCP) is reliable for detecting biliary complications, with one meta-analysis demonstrating sensitivity 96% and specificity 94%.25 Many patients will go on for endoscopic retrograde cholangiography (ERC), with GI consult and admission.22-25

Stricture

Strictures come in two forms: anastomotic or nonanastomotic. Anastomotic stricture occurs within the first year after surgery.22,23,26-29 Nonanastomotic stricture may be due to vascular injury, stone formation, or infection. Ultrasound with Doppler evaluation has a sensitivity ranging from 38% to 66%, with definitive imaging involving MRCP or ERC.22,23,26-29 Treatment requires ERC with stent placement, though surgical revision may be required. 22,23,26-29

Bile Leak

Bile leaks occur in 2% to 25% of patients.22,23,29,30 Leakage may occur at the anastomosis, along the bile duct, or the liver surface. Early leaks occur at the anastomotic site. 22,23,29,30 ERC is required for diagnosis and at times treatment with stent placement.30-33 Late leaks occur with removal of part of the surgical equipment. ERC is required, with stenting. Intraductal obstruction can be due to gallstone, sludge, blood clot, cast, or migrated stent.30-36 These often occur late after transplant and are diagnosed on ERC.30-36 Small leaks in a stable patient who displays minimal symptoms may be followed with repeat imaging.22,23, 30-36

Biloma

Bilomas are postoperative collections of bile that are often perihepatic. These are commonly due to bile duct rupture and cause serious complications.22,23,30-36 If the bile collection communicates with the biliary tree, the fluid will reabsorb. However, large bilomas that do not communicate should be managed with percutaneous drainage and broad-spectrum antibiotics. US can suggest the diagnosis in the ED with loculated fluid collection, but endoscopy is definitive.22,23

Heart Transplant

Cardiac transplant is definitive for end-stage heart failure, with over 5,000 transplants conducted annually worldwide.1,2,37 Sympathetic and parasympathetic nerves are severed during transplant, resulting in loss of vagal tone.37-40 Close to one third of patients at one year post-transplant have partial reinnervation.38-40 Resting heart rate ranges from 80-110 bpm.37-40 Within the first year of transplant, graft failure, acute rejection, and infection account for the majority of complications.

Vasculopathy

After the first year post-transplant, cardiac allograft vasculopathy is a major cause of graft failure. This is due to rapid atherosclerosis in the heart and occurs in up to 70%.37 The disease usually progresses slowly, but rapid progression may involve multiple coronary vessels in acute rejection. The disease is due to immunologic and non-immunologic mechanisms with intimal proliferation of grafted coronary vessels.39-41 It is usually asymptomatic, but patients may present with myocardial infarction (MI). The tricky aspect is that the patient may not have chest pain due to denervation.39-41 Instead, the patient may experience diaphoresis, dyspnea, syncope, palpitations, nausea/vomiting, and even sudden death.39-41 The ECG can be difficult to interpret due to baseline abnormalities.41,42 US of the heart is needed to assess function, with cardiology and transplant consultation. Laboratory examination may include C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-pro BNP), and troponin elevation.42,43 Unfortunately, the atherosclerosis is often diffuse with concentric narrowing.43-47 Treatment requires bypass surgery or a second transplant.43-47

Dysrhythmia

Cardiac dysrhythmia is common following transplant due to SA and AV node damage, ischemia, rejection, and accelerated atherosclerosis.47,48 The denervated heart possesses increased sensitivity to sympathomimetic agents.47-49 Premature atrial and ventricular complexes occur in 60% to 76% of patients. Other dysrhythmias include bradycardia, atrial flutter and fibrillation, atrioventricular block, and ventricular ectopy.50-52 Bradycardia can occur with sinus node dysfunction, most commonly as a result of surgical trauma.53 Atropine is not effective due to loss of vagal innervation.53 Epinephrine or isoproterenol IV can be used. If the patient is unstable in the ED, transvenous pacemaker is needed.51,52,55 Conduction delay, including new RBBB, accounts for 70% of dysrhythmias after transplant.51,52 High grade atrioventricular blocks are uncommon, but if the patient is unstable, a transvenous pacemaker is needed.56-58

Atrial flutter or fibrillation occurs in up to 24% of patients, usually with rejection. 51,52,56-58 These dysrhythmias are associated with increased mortality risk. Atrial fibrillation occurring without rejection is due to structural damage and macroreentrant circuit. If unstable, the patient requires cardioversion. Stable patients should receive a beta-blocking agent for rate control.56-58 Calcium channel blockers should be avoided due to immunosuppressive medication interaction. Supraventricular tachycardia requires cardioversion if unstable.51,52 Remember, adenosine at half the normal dose (3 mg IV) should be provided, as the denervated heart is more sensitive to the medication. Vagal maneuvers are ineffective due to denervation.51,52,55 Ventricular dysrhythmias may occur due to rejection and atherosclerosis, and sustained dysrhythmias require cardioversion.59-61

Lung Transplant

 Mechanical Complications and Obstruction

Lung transplant provides definitive treatment for end-stage lung disease. Transplant includes three anastomoses: airway, pulmonary arterial, and pulmonary vein to left atrium.2,3 The airway anastomosis is the most vulnerable site for complication, especially in the first year, with rates ranging from 2% to 33%.62,63 This is thought to be due to loss of blood supply to the site, which requires 4 weeks for regrowth. Airway complications may present with dyspnea, wheezing, stridor, or postobstructive pneumonia.62,63 Obstructions include bronchial stenosis, which occurs after the first transplant month. Intubation may be required for severe symptoms and respiratory failure. CT and bronchoscopy are needed.64,65 Fistula formation may produce pneumothorax, subcutaneous emphysema, respiratory distress, and hypotension. CT scan is required for diagnosis and management, with transplant surgeon consult.64,65

Vascular Complications

Vascular complications are less frequent than airway anastomotic complications, but when they occur they have serious consequences.65-67 Stenosis, kinking, and thrombus formation are major vascular complications. Pulmonary artery stenosis may occur early and late after the transplant, while vein thrombosis occurs early.66-68 Patients present with hypoxemia, edema, dyspnea, and hypotension.67,68 Bedside US will demonstrate signs of right heart strain or failure.69,70 CT angiography is usually needed for diagnosis.70-72 Stenosis can be treated with balloon dilatation and stent placement, kinking with metallic stenting, and thrombosis with systemic anticoagulation.70-74 If the patient is hemodynamically unstable with thrombus, systemic thrombolysis is needed.70-74

Phrenic Nerve

Phrenic nerve dysfunction occurs in 3% to 9% of cases, though it is more common in combined heart-lung transplant (40%).75,76 Dyspnea, hypoxemia, tachypnea, and hypoventilation are common presenting symptoms or signs, while atelectasis and hemidiaphragm elevation on Xray are suggestive. 75,76 Diagnosis often requires fluoroscopic examination, which is not obtainable in the ED. Unilateral diaphragm dysfunction is often asymptomatic, requiring no treatment. Bilateral diaphragm paralysis leads to progressive respiratory failure and often necessitates mechanical ventilation.75,76 Diaphragmatic plication can be used for severe symptoms.

Pleural Complications

Other complications include pneumothorax, hemothorax, and chylothorax.77-79 Effusions are most commonly due to infection, rejection, or malignancy. These conditions often present with dyspnea, chest pain, and respiratory distress in severe effusions. Chest radiograph may suggest the diagnosis, and US can assist. CT is definitive for localization, but aspiration of the effusion is required for fluid characterization, though this is not required in the ED.77-79

Summary

– Beware the transplant patient: involve the transplant physician, transplant surgeon, and specific organ consultant for evaluation and management.

– Renal complications post-transplant include infection, vascular obstruction, hematoma, ureteral obstruction, and lymphocele. Patients often present with edema, decreased urine output, and increased serum Cr.

– Liver transplant complications include vascular obstruction, biliary conditions (stricture, leak, biliary stone, fluid collection), biloma, and stricture.

– Cardiac transplant is associated with denervation, thus patients often do not present with chest pain, but symptoms of CHF including edema. Complications include vasculopathy with accelerated atherosclerosis and cardiac dysrhythmia.

– Lung transplant requires three anastomotic connections. Patients may experience obstruction, vascular complications, phrenic nerve dysfunction, and pleural lining complications.

 

References/Further Reading

  1. 2012 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 2012. Department of Health Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD; United Network for Organ Sharing, Richmond, VA; University Renal Research and Education Association, Ann Arbor, MI.
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  3. Venkat KK, Venkat A. Care of the renal transplant recipient in the emergency department. Ann Emerg Med 2004 Oct;44(4):330-41.
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  9. Rengel M, Gomes-Da-Silva G, Inchaustegui L, et al. Renal artery stenosis after kidney transplantation: diagnostic and therapeutic approach. Kidney Int. 1998;54(Suppl 68):S99-106.
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