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Author: Jaime Shalkow, MD, Head of Surgical Oncology, Division of Surgery, National Institute of Pediatrics, Mexico; Head-Professor of Pediatric Surgical Oncology, Universidad Nacional Autonoma de Mexico

Coauthor(s): Nicholas A Shorter, MD, Professor of Clinical Surgery and Clinical Pediatrics, State University of New York-Downstate University; Division Chief, Department of Surgery, Division of Pediatric Surgery, State University of New York-Downstate Medical Center; Nayomi K Edirisinghe, MD, Instructor, Department of Surgery, Harvard Medical School; Consulting Staff, Cambridge Breast Center, Department of Surgery, Cambridge Health Alliance; Brian F Gilchrist, MD, Chief, Division of Pediatric Surgery, Tufts-New England Medical Center; Associate Professor, Department of Surgery, Tufts University School of Medicine; Marc S Lessin, MD, Consulting Surgeon, Children's Surgical Associates, PC

Editors: Jonah Odim, MD, PhD, MBA, Senior Medical Officer, Transplantation Immunology Branch, Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; John Myers, MD, Director, Pediatric and Congenital Cardiovascular Surgery, Departments of Surgery and Pediatrics, Professor, Penn State Children's Hospital, Milton S Hershey Medical Center; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; Mary C Mancini, MD, PhD, Director of Cardiothoracic Transplantation, Professor, Department of Surgery, Louisiana State University Health Sciences Center

Author and Editor Disclosure

Synonyms and related keywords: iatrogenic vascular lesions, thrombosis, thromboembolism

The word iatrogenic comes from Greek iatrós, meaning medicine or doctor, and guennan, which means produced by. Therefore, iatrogenic refers to the consequences of the medical action. In general, an iatrogenic injury is secondary to a high-risk procedure when a lower-risk option available; to a lack of medical knowledge, negligence, careless practice, or omission; or to the lack of honesty or medical ethics.

The introduction and proliferation of invasive neonatal resuscitation techniques has led to an increased incidence of vascular complications in the pediatric population. The risk of iatrogenic vascular injuries secondary to catheterization, repeated venipuncture, or arterial blood sampling has increased. In particular, transfemoral catheterization, transfemoral arteriography, and umbilical-artery catheterization used for diagnostic and monitoring purposes have been associated with thromboembolism in the lower extremities. The management of these injuries in infants and small children is distinctly different from that in adults. The small size of their vessels, severe arterial vasospasm, and the consequences of diminished blood flow on limb growth must be considered.

Frequency

Trauma has replaced infectious diseases as the main cause of death in the children and adolescents aged 1-14 years, and it has become a public health problem in many parts of the world. Traumatic vascular lesions, though rare in the pediatric age group, account for 3.3-6.3% of admissions in large trauma centers.

Two thirds of pediatric arterial injuries are iatrogenic. The incidence of iatrogenic arterial injuries is increasing, especially in children younger than 2 years. Rates of arterial injury from transfemoral cardiac catheterization are 26-67%.

The incidence of thrombosis after the use of umbilical-artery catheters is unknown. However, several reviews indicate a major complication rate of 17-20%. In 1 study of 4000 infants with an umbilical-artery catheter, 41 developed a major thromboembolic complication, an incidence of less than 1%. Arterial complications of umbilical-artery catheters include vasospasm, aortic thrombosis, partial or complete iliac-artery thrombosis, or embolism to peripheral and visceral tissues. The position of the umbilical-artery catheters may affect the frequency of thromboembolisms. The tips of umbilical-artery catheters may be positioned high (ie, at the level of T5-T10) or low (ie, at the level of L3-L5). The optimal position to minimize thromboembolisms remains uncertain.

Arteriovenous fistulas secondary to multiple arterial punctures in neonates are rare.

Age and size are important risk factors for arterial injuries. Infants who weigh less than 10 kg have an increased incidence of vessel obstruction after cardiac catheterization. One study demonstrated an increased incidence of thromboembolism secondary to transfemoral cardiac catheterization in children younger than 10 years than in children older than this. An Italian study of 2898 neonates admitted to the neonatal intensive care unit in 1987-1994 demonstrated a higher risk of iatrogenic vascular injuries in neonates with extremely low or low birth weight (2.6%) than in older neonates (0.3%).

Different types of catheters used in the pediatric age group have specific associated complications.

Central venous catheters (CVCs) can lead to serious and sometimes life-threatening complications. CVCs are associated with an overall complication rate of 42-80%, including mechanical, infectious, or thrombotic events. The choice of insertion site can influence the incidence and type of complications. The coagulation cascade is activated by the mere presence of a catheter in the vein, which provokes physic and chemical changes in the vascular endothelium, with hemodynamic alterations. These devices are often used in children with hematologic malignancies and hypercoagulable states.

One study revealed fibrin deposits around the catheter in 100% of patients who died while they had a CVC. Complications reported with these vascular devices include infection, incorrect placement, phlebitis, vascular dissection, pneumothorax, thrombosis, migration, pericardial or pleural effusion, chylothorax, peritoneal or retroperitoneal extravasation, cardiac arrhythmias, endocarditis, and pulmonary embolism.

Mechanical complications include arterial puncture, pneumothorax, hemothorax or mediastinal hematoma, misplacement of the catheter tip, puncture site hematoma or bleeding, and air embolism. (About 0.5-1 mL/kg of air suffices to produce an air embolism in a child.)

A randomized controlled trial showed that catheterization of the femoral vein was associated with a significantly increased risk of overall complications compared with catheterization of the subclavian vein, with an increased risk of catheter-related infection and thrombosis. Risk factors for catheter-related mechanical complications included the time needed for catheter insertion (number of needle passes), insertion during the night (operator fatigue or inexperience), and a center effect.

The femoral site has a 5-fold increased incidence of catheter-related infectious complications compared with the subclavian approach. This risk can be reduced with the use of subcutaneous tunneling, antibiotic impregnated catheters, and a catheter for systemic antibiotics.

The femoral approach also has an increased incidence of thrombotic complications (21%) compared with the subclavian catheters (1.9%). Some studies have shown that subclavian catheterization should be preferred to the use of femoral lines whenever possible.

Patients with severe refractory hypoxemia may be at increased risk when the subclavian route is used, whereas patients with morbid obesity may be at high risk with femoral cannulation.

Cardiac catheterization has a complication rate of 4-8%. Complications include trapping of the angioplasty balloon, vascular tears, lesions of the left pulmonary artery, mitral valve injury, coil migration, embolization, bleeding, and vascular laceration or perforation.

Lin and Dodson (2001) reported on 1674 pediatric cardiac catheterizations preformed with a femoral approach. Iatrogenic inguinal lesions that required surgical repair occurred in 2%, with an overall morbidity rate of 12% and a mortality rate of 3%.

Finally, with advances in interventional catheterization, the use of large catheters and sheaths increase the risk even further.

Etiology

The most common etiology of arterial thromboembolism in children is the use of catheters, including those for transfemoral cardiac catheterization, umbilical-artery catheters, and those for central or peripheral arterial lines. The mere presence of a catheter in a blood vessel is a risk factor for complications. Pediatric iatrogenic vascular lesions are secondary to arteriography, cardiac catheterism, arterial puncture, repeated blood samples, vascular access, or foreign bodies (eg, fractured or displaced guidewires or catheters). Neonatal thrombosis has been described in association with radial, femoral, pulmonary, and temporal artery lines, as well as with catheters in the femoral and jugular veins.

Surgical procedures are also a risk factor for vascular injury. Surgery-related lesions largely result from orthopedic procedures, and tumor resections performed by urologic and oncologic surgeons, who frequently perform large dissections in areas with distorted anatomy.

Appropriate arterial access is needed to manage severe congenital heart malformations. This access should be achieved by following strict protocols, with a limited number of punctures carried out by experienced staff and only in large arteries. Residents in training should start developing their skills in large patients in relatively stable condition, and they be supervised at all times. When a vascular lesion occurs in this setting, an endovascular approach is preferred first. If this fails, a surgical approach is required in the shortest time possible.

Pathophysiology

The usual sequence is arterial puncture, followed by spasm and thrombotic occlusion. The vascular endothelium has a predominant role in blood coagulation, and it has numerous interactions with perivascular cells and adjacent tissues. Several conditions predispose neonates to thrombotic complications, including congenital heart disease, polycythemia, sepsis, maternal diabetes or toxemia, dehydration, and low-flow states. Neonates also have lowered concentrations of antithrombin III, proteins C and S, and heparin cofactor II that result in a prothrombotic state. Evidence also suggests that fibrin sleeves form on catheters. Stripping of the sleeve with removal of the catheter may result in subsequent occlusion at the puncture site or distal embolization.

In a 32-month study, investigators monitored 76 children with regard to iatrogenic injury and found that all injuries involved the arteries of the lower extremities. This finding is consistent with the trend away from puncture of the brachial artery for invasive diagnostic and monitoring procedures. In particular, the arterial injury is often at the level of the common femoral artery secondary to multiple attempts at arterial access in the groin.

In pediatric patients, iatrogenic vascular injuries associated with use of the femoral approach can be divided in ischemic and nonischemic injuries. The former can be further subdivided as acute or chronic. Acute ischemia occurs in 41.2% of patients, whereas chronic ischemia is reported in 20.6%. Nonischemic injuries include pseudoaneurysms, arteriovenous fistulae, hemorrhage, and hematomas.

Umbilical-artery catheters may perforate or tear the vessel, producing bleeding or aortoiliac occlusion due to thrombosis with microembolization and thus occluding a visceral artery.

Clinical

Pediatric iatrogenic vascular lesions can be acute or manifest late.

Signs and symptoms of vascular injuries are usually apparent immediately. Patients with limb ischemia present with the classic signs of distal hypoperfusion, or cold skin plus the 5 Ps: pulselessness, pallor, paralysis, paresthesia, and pain. Pulses can be difficult to palpate in infants and small children. However, Doppler technology can be used to confirm flow and compare pressures to the contralateral uninvolved limb.

Signs may be transient or may progress quickly to gangrene. Vascular spasm in children is inversely proportional to the size and age of the patient. Simple spasm usually subsides spontaneously within 3 hours. However, lesions suggestive of vascular compromise should not be attributed to spasm. The presence of pulses distal to the lesion does not completely rule out a vascular injury because as many as 25% of patients may have distal pulses even in the presence of a vascular insult.

Patients with certain vascular injuries have a late presentation. Patients with arteriovenous fistulae, mycotic aneurysms, pseudoaneurysms, renal vascular occlusion with renovascular hypertension, intermittent claudication, or growth retardation of the affected extremity present with subtle signs and symptoms. Particular attention must be paid to poor capillary refill, coolness, diminished pulses, bruits, thrills, blanching, bluish discoloration, lack of movement, and mottling.

Not all patients with thrombosis develop clinical symptoms. On occasion, the vessel is only partially blocked, and collateral blood flow is adequate. This occurs with thromboses that are associated with umbilical-artery catheters. In a series of 4000 patients, only 1% of patients developed clinical symptoms of thrombosis. Patients with acute aortic thrombosis secondary to umbilical-artery catheters can present with hypertension or congestive heart failure.



Only a few absolute indications exist for surgical intervention in children with iatrogenic vascular injuries. Any child with a nonviable limb should be taken to the operating room for definitive repair. Cases involving vascular injury, a lack of flow on Doppler study, or signs of neurologic deficit should be explored surgically. Late repair may be undertaken before the adolescent growth spurt occurs in some children with limb-length discrepancies.

Three strategies have been described and are based on the type of injury. Type I refers to life-threatening or limb-threatening lesions (hard signs). Patients with type I injuries require immediate surgical exploration. Type II includes lesions that do not immediately jeopardize limb integrity and that are not life-threatening; however, a vascular injury is evident. If available, Doppler study or preoperative angiography is the best first step. Otherwise, angiography can be performed during surgery. Type III includes the injuries without hard signs. However, because of their location and mechanism of injury, a vascular lesion should be suspected. These are best approached with angiography or CT angiography.

Acute aortic thrombosis is another absolute indication for surgery. Nonoperative therapy is associated with a 100% mortality rate, and several reports describe success with surgery for aortic thrombosis.

As surgeons become increasingly competent in repairing small vessels, the relative indications for repairing pediatric vascular lesions will increase.



With umbilical-artery catheters, the pathway is through 1 of the 2 umbilical arteries into the internal iliac artery, the common iliac artery, and then the aorta. With transfemoral catheterization, the injury is at the level of the common femoral artery.



Most neonates and children in the intensive care setting are poor surgical candidates because of their medical illnesses. In this case, the risks of surgery must be weighed against the risk of limb loss and limb growth discrepancy. If surgery is contraindicated, medical therapy, ie, heparin or thrombolytic agents, can be started.



Imaging Studies

  • The diagnosis of a vascular insult must be made promptly so that the appropriate treatment can be initiated. Most often, the diagnosis is made clinically. However, noninvasive studies are helpful.
  • Doppler-derived segmental lower-extremity measurements of arterial pressure have been used to confirm injury.
  • For imaging aortoiliac injuries, Doppler ultrasonography and radioisotope arteriography have been useful in assessing patency.
  • Doppler echography has proven useful in the diagnosis of arteriovenous fistulas.
  • Arteriography is rarely used because this modality can cause further complications.
  • Digital subtraction arteriography and high-resolution ultrasonography are relatively new techniques that may further facilitate the diagnosis and management of these injuries.



Medical therapy

The principles of managing peripheral vascular injuries in children are different from those of adults. Severe arterial spasm and the long-term effects of diminished blood flow on limb growth must be considered. The arterial spasm compromises repair of an arterial injury. Therefore, with children, deferring arterial repair until the limb is immediately threatened is best. If surgery is not performed, monitoring limb length over time and repairing the artery if a significant discrepancy develops is important. This monitoring and repair should be performed before the adolescent growth spurt occurs.

The first maneuver in treating vascular injury is removing the inciting factor. The catheter should be removed promptly when signs of ischemia develop. It should not be replaced at the same site, even if the signs revert.

Infants who lose their lower-extremity pulses after transfemoral catheterization often regain the pulses after 1-2 days. Collateralization is more rapid in infants than in adults, and because of this capacity, anticoagulation and observation are preferred in this type of injury when the extremity has preserved sensibility and movement and when a Doppler signal is audible. If the lesion is of venous origin, elevating the extremity is appropriate to accelerate the resolution of edema. If the injury in question is arterial, lowering the extremity and keeping it warm produces vasodilation and improves circulation. The risks of surgery must be weighed against the risk of limb loss or limb growth discrepancy.

In cases of chronic ischemia (>30 d), arteriography is indicated. Patients clinically present with claudication and extremity growth retardation, which is considered clinically significant when the discrepancy between the extremities reaches 2-3 cm. Even if the pulses do not recover, if the ankle-arm index is adequate and if the patient is asymptomatic, no surgical intervention is required.

Similarly, thrombosis associated with umbilical-artery catheters should be managed with anticoagulation and catheter removal.

Immediate heparinization with 15-25 U/kg/h given intravenously (IV) after an IV bolus of 50 U/kg reduces the propagation of thrombus. In a study in which 76 children were monitored for 32 months, a set of guidelines was established for initial medical management of vascular injuries. Any patient who did not regain femoral pulses when the catheter was removed immediately received heparin and was observed for 6 hours. If femoral pulses were still absent after 6 hours, surgery was performed. If femoral pulses returned but distal pulses were absent, heparin therapy was continued.

Thrombolytic agents, such as urokinase, have been used with success in neonates. In the above-mentioned study, 2 neonates who were not candidates for surgery received heparin and urokinase for iliac-artery thromboses secondary to umbilical-artery catheters. In both cases, normal circulation was present at 13 and 18 months without a limb-length discrepancy. A loading dose of 4400 U/kg of urokinase is typically administered with a maintenance infusion of 100-50,000 U/kg/h, depending on whether the treatment is administered systemically or directly into the clot.

In addition to urokinase, streptokinase and tissue plasminogen activator (alteplase) restore flow rapidly.

In children undergoing cardiac catheterization, prophylactic anticoagulation therapy with heparin 100-150 U/kg reduced the incidence of thromboembolism from 40% to 8%. A small randomized trial demonstrated that heparin 50 U/kg tended to be as effective as 100 U/kg when administered immediately after arterial puncture.

In children undergoing cardiac catheterization, prophylactic anticoagulation with aspirin does not significantly reduce the incidence of arterial thromboembolisms. However, for the ambulatory setting, children can be given low-dose aspirin 4-5 mg/kg/day as a platelet antiaggretator.

Surgical therapy

The goal of surgery is to restore vascular supply to ischemic territories. The goal of surgery is to restore vascular supply to ischemic territories. Surgical repair can be accomplished by means of thromboembolectomy, patch angioplasty, primary anastomosis, or bypass grafting. When the injury exceeds 30% of the circumference of the vessel, surgical repair should be performed with other means rather than simple closure, such as vein patching or grafting.

In the rare circumstance of acute aortic thrombosis, aortic thrombectomy is the procedure of choice when patients' conditions are deteriorating, with worsening congestive heart failure and hypertension, intestinal ischemia, renal failure, lower-extremity ischemia, and multiorgan failure. A transabdominal approach allows for a bowel resection if needed.

One report describes a transverse incision at the aorta above the iliac bifurcation. A 3F balloon catheter may then be used to extract the clot from the iliac arteries. A 2F balloon catheter may be used for the femoral arteries. To gain control of the renal orifices, longitudinal aortomy may be necessary. Interrupted sutures are used to close the incision; they allow for subsequent arterial growth. In particular, 7-0 polypropylene sutures have been used to close the aorta.

Thromboembolectomy alone suffices in 43% of patients, and 14% of the patients require surgical repair with arteriography with or without resection of an arterial segment. About 71% of patients recover their pulses, whereas 57% have audible Doppler signals and never regain their pulses. Therefore, follow-up is clinically done by periodically measuring the ankle-arm index. The most common complications after surgical repair are surgical wound infection and arterial rethrombosis. Surgical wound infection is reported to occur in 3-22% of cases and depends on several factors including age, associated fractures and soft tissue trauma, albumin level, and time elapsed before repair. Arterial rethrombosis is reported to occur in 14% of patients.

Surgical principles to bear in mind when repairing a vascular injury include the following:

  • Widely prepare the surgical field, including both legs in anticipation of the need to use venous grafts.
  • Obtain good exposure and vascular dissection to achieve proximal and distal control of the injured vessel.
  • After extracting the clots, use heparin in the segments to be anastomosed.
  • Identify and isolate the collateral vessels, maintaining their integrity.
  • Resect nonviable tissue. Do not perform anastomoses when the intimal layer is detached.
  • Cover the anastomosis with healthy soft tissue.
  • Liberally use fasciotomy when indicated. For repairs being performed longer than 6 hours after the injury, consider associated venous lesions and the possibility of massive edema with compartment syndrome.
  • Always try to repair the vein, if injured.
  • Perform surgical arteriography at the end of the procedure.

Pseudoaneurysms can be treated with percutaneous embolization if they have a small neck.

For arteriovenous fistulas, dissection of both vessels and closure of the communication is the procedure of choice.

With the advent of improved suture and graft material and the development of microsurgical techniques, more arterial injuries are addressed in the operating room now than before. With atraumatic vascular clamps and needles, 9-0 to 11-0 nylon sutures are used for vascular anastomoses. Topical application of 2% lidocaine (Xylocaine) or papaverine is used to control vasospasm. Prophylactic antibiotics are used preoperatively. Ipsilateral reverse saphenous vein grafts are used for all reconstructions of femoral arteries. The dorsal veins of the foot, which have a thick muscularis, can also be used as grafts. Debriding the injured arterial segment completely is crucial in preventing subsequent thrombosis.

In the postoperative period, closely monitor distal neurovascular compromise of the extremity, checking the patient's pulse, color, temperature, and capillary refill. Do not use compressive bandages, and look for edema. Keep the extremity mildly flexed, and initiate movement or ambulation as soon as possible.

Follow-up

Only a few investigators have used objective methods to document graft patency long term. In 1 report, a child was monitored by using pulse-volume recordings for graft patency and low-dose digital radiography for limb growth. The child had a 1-cm limb discrepancy in the revascularized leg after 6 years. Both Doppler studies and pulse-volume recordings demonstrated severe stenosis of the graft despite initial successful revascularization.

Follow-up studies to demonstrate protection of limb length with medical and surgical treatment would be beneficial if conducted.



Gangrene and loss of a limb secondary to arterial insufficiency in young children are rare. However, limb shortening and claudication are frequent complications of femoral-artery thromboembolisms in children. Approximately 10% of children have symptoms or limb-length discrepancy when monitored long term.

Many iatrogenic vascular injuries are due to lack of knowledge of the anatomy, physiology, surgical technique, and management strategies with the various vascular devices. Possible complications range from a simple hematoma or a self-limited phlebitis to patient death. Therefore, clinicians must always be well informed, continue to review these topics, and have contact with medical personnel with good training and experience in treating these patients to prevent and minimize such complications.



Serious complications, such as gangrene or limb loss, are rare. However, approximately 10% of children develop symptoms and/or limb-length discrepancy. Therefore, limb length should be monitored and surgery performed if a discrepancy is found before the adolescent growth spurt occurs.



Follow-up studies to demonstrate protection of the limb by medical and surgical treatment of iatrogenic vascular injuries would be beneficial if done.



Media file 1:  Right-hand gangrene and necrosis secondary to use of a brachial-artery catheter in very-low-birth-weight baby girl.
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Media type:  Photo

Media file 2:  Superior vena cava syndrome in a patient with an intravenous access device (Port-A-Cath) in the right subclavian vein. Note the facial and upper torso edema, and the prominent collateral veins.
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Media type:  Photo

Media file 3:  Close up of the same patient with the Port incision and prominent collateral veins characteristic of superior vena cava syndrome secondary to catheter-related thrombotic complication.
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Media type:  Photo

Media file 4:  Caval venogram depicts considerable narrowing of the infradiaphragmatic vena cava secondary to a right hepatic trisegmentectomy. The patient developed a mild inferior vena cava (IVC) syndrome, was treated nonsurgically (with heparinization), and recovered adequately, developing a collateral circulation without sequelae.
Click to see larger pictureClick to see detailView Full Size Image
 
Media type:  Movie



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Iatrogenic Vascular Lesions: Surgical Perspective excerpt

Article Last Updated: Oct 16, 2006