Practice Essentials
The term iatrogenic derives from the Greek words iatros ("physician") and gennan ("to produce"); thus, the term refers to the consequences of medical action. In general, an iatrogenic injury is secondary to one or more of the following:
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Performance of a high-risk procedure when a lower-risk option is available
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Lack of medical knowledge, negligence, careless practice, or omission
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Lack of honesty or medical ethics
Iatrogenic injuries account for a significant proportion (50%) of pediatric vascular trauma. The proportion inversely varies with age, being highest in neonates (80%) and declining to 50% in the 2- to 6-year-old group and to 33% in older children.
Arterial injuries in infants are rare and, in most cases, iatrogenic as a consequence of catheterization, venipuncture, or arterial blood gas (ABG) sampling. These lesions require an accurate, noninvasive clinical diagnosis and prompt exploration and reconstruction with microvascular techniques to restore perfusion and avoid morbidity and even mortality. In this age group, any suspected vascular injury calls for immediate clinical and diagnostic assessment to avoid potential life-threatening complications. Surgery is mandatory in the case of extensive arterial injuries, inadequate distal blood supply, or progressive worsening of ischemic clinical findings. [1]
The widespread use of percutaneous vascular access in children and invasive neonatal resuscitation techniques has led to an increased incidence of vascular complications in the pediatric population. The thrombosis rate in children with vascular access ranges from 1% to 25%. [2, 3]
The risk of iatrogenic vascular injuries secondary to catheterization, cannulation for extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass (CBP), repeated venipuncture, or ABG 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.
Although management of these injuries has evolved over time, it is not yet standardized in children. Treatment of these injuries in infants and small children is distinctly different from that in adults. Historically, injured vessels were ligated, or the child was given systemic heparin without repair; however, this expectant therapy resulted in poor limb outcomes, involving high amputation rates and diminished limb growth. Subsequent study determined that aggressive surgical management yields better results, making early diagnosis followed by definitive repair the approach of choice at present. [2]
In children, the small size of the vessels, severe arterial vasospasm, and the consequences of diminished blood flow on limb growth must be considered. Moreover, the need for future growth of blood vessels and long-term duration of the repair must be accounted for.
Follow-up studies to demonstrate protection of the limb by medical and surgical treatment of iatrogenic pediatric vascular injuries are needed. With the advent of newer technology and the clinical possibilities that it offers, the management of these injuries will continue to evolve. There is no doubt that the use minimally invasive techniques will continue to expand.
Anatomy
Certain anatomic factors contribute to the high rates of iatrogenic vascular injury in children. Anatomic variations occurring in the pediatric population, such as angulation of the major access veins (ie, the femoral vein and the internal jugular vein [IJV]) and overlap of arteriovenous structures, must be considered. [4] Access via the IJV or the subclavian vein appears to be associated with a high risk of arterial puncture. [4, 5] Vascular access placed at or below the ankle has been found to carry an increased risk of thrombosis. [5]
In addition, the small caliber of the vasculature and the increased mobility of the vessels contribute to the increased risk of iatrogenic vascular injury. [4] Accordingly, the size and characteristics of a vascular access device must be carefully considered in this population. Catheters with multiple lumens or with a diameter exceeding 50% of the arterial diameter may result in spasm and low flow rates, rendering vessels prone to thrombosis. [2, 4]
With umbilical artery catheters, the pathway is through one of the two 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.
Pathophysiology
Pediatric iatrogenic trauma usually occurs as a result of inadvertent arterial puncture, leading to spasm and thrombotic occlusion. The vascular endothelium has a predominant role in blood coagulation and has numerous interactions with perivascular cells and adjacent tissues. The presence of a catheter in a vessel activates the coagulation cascade, which provokes physical and chemical changes in the vascular endothelium. Additionally, trauma to the endothelial lining secondary to vascular access is prothrombogenic. [6]
The lower total blood volume and increased propensity for vasospasm in children also contributes to the higher rate of iatrogenic vascular complication in the pediatric population as compared with the adult population. [4] Furthermore, vascular access devices are often used in children with hematologic malignancies and hypercoagulable states.
Several conditions predispose neonates to thrombotic complications, including congenital heart disease with poor cardiac function, polycythemia, sepsis, maternal diabetes or toxemia, dehydration with low intravascular volume, and low-flow states. Neonates also have lowered concentrations of antithrombin III, proteins C and S, and heparin cofactor II, which 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. [7] This finding is consistent with the trend away from puncture of the brachial artery for invasive diagnostic and monitoring procedures. In particular, arterial injury is often at the level of the common femoral artery secondary to multiple attempts at arterial puncture in the groin.
In neonates, use of umbilical artery catheters may result in perforation or dissection of the access vessel. This is associated with a high risk of bleeding and thrombosis, which may result in aortoiliac occlusion.
Etiology
The most common etiologic factor for arterial thromboembolism in children is the placement of catheters, including those used for transfemoral cardiac catheterization, umbilical artery catheters, and central or peripheral arterial lines. The mere presence of a catheter in a blood vessel is a risk factor for complications.
Iatrogenic pediatric vascular trauma is typically secondary to arteriography, cardiac catheterization, repeated venipuncture, insertion of vascular access devices, or foreign bodies (eg, fractured or displaced guide wires or catheters). [4] 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. Arterial tears are a rare but potentially lethal complication of central venous catheter (CVC) placement.
Surgical procedures are also a risk factor for vascular injury. Surgery-related iatrogenic vascular injuries are largely associated with orthopedic procedures and oncologic tumor resections. These procedures often involve large dissections in areas with distorted anatomy or disrupted dissection planes and may include resection of highly vascularized lesions. Furthermore, perivascular tumors preoperatively treated with chemotherapy, radiation therapy, or both commonly exhibit thinning of the muscular layer of the vessel wall, with fibrosis of the adventitia into the surrounding tumor, which makes vessels prone to injury during subadventitial-plane dissection.
The use of partial nephrectomy or nephron-sparing surgery (NSS) has gained popularity in patients with renal tumours because the disease-free survival rates are similar between radical nephrectomy and NSS. Pseudoaneurysms, arteriovenous fistulas (AVFs), and hemorrhage due to vascular lacerations have been reported in these patients. [8, 9] The interventional radiologist plays a key role in the management of such lesions because most can be successfully treated with endovascular techniques.
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 performed by experienced staff and only in large arteries. Residents in training should start developing their skills in larger patients who are stable, and they must be supervised at all times.
Hypotension during or immediately after a jugular or subclavian puncture should be a warning of a serious event, usually a massive hemothorax. When a vascular lesion occurs in this setting, an endovascular approach is initially preferred because it has been demonstrated to be successful in most instances. If this fails, a surgical approach is required in the shortest time possible.
Epidemiology
Trauma is the leading cause of death in children and adolescents aged 1-14 years and has become a public health problem in many parts of the world. Traumatic vascular injury, though rare in the pediatric age group, accounts for 3.3-6.3% of admissions in large trauma centers.
Iatrogenic vascular trauma accounts for 50% of all pediatric vascular injuries. [4] The incidence of such trauma is increasing, especially in children younger than 2 years, with a wide range (2-67%) reported in the current literature. [4]
Younger patient age, weight, comorbidities (eg, cardiac dysfunction and renal failure), and previous abdominal surgery are predisposing factors for iatrogenic vascular trauma. [4] Infants weighing less than 10 kg are at an increased risk 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 as compared with older children. An Italian study of 2898 neonates admitted to a neonatal intensive care unit (NICU) demonstrated a higher risk of iatrogenic vascular injuries in those with extremely low or low birth weight (2.6%) as compared with those who were older or heavier (0.3%). [10]
Procedural factors (eg, larger-caliber devices, certain catheter characteristics, repeat instrumentation, and exchanges) also increase the risk of iatrogenic vascular injury. Additionally, the different anatomic locations and different types of catheters used in the pediatric age group have specific associated complications.
In pediatric patients, iatrogenic vascular trauma may result in hemorrhage or hematoma formation, arterial dissection, thrombosis, pseudoaneurysm, or AVF formation. [4] These iatrogenic injuries may lead to ischemic and nonischemic complications. Ischemic complications can be subdivided into acute and chronic limb ischemia. [4]
Reports of inadvertent arterial puncture following vascular access procedures are highly variable and range from 0.2% to 32% in the literature. [4] The risk of arterial puncture is highest with IJV and subclavian vein access, followed by femoral and great saphenous vein (GSV) access. [4, 6] This may result in hematoma formation or hemorrhage, with a reported incidence as high as 9% in central venous access procedures. [4]
Although unrecognized iatrogenic arterial injury can lead to arterial thrombosis, pseudoaneurysm, or AVF formation, AVF and pseudoaneurysm secondary to iatrogenic vascular trauma are rare in children, with reported incidences of 0.3% and 0.01%, respectively. [4] In contrast, arterial thrombosis, particularly involving the femoral artery, is a more commonly reported complication, with an incidence of 2-3%. [4]
The incidence of thrombosis after the use of umbilical artery catheters is unknown. However, several reviews have indicated a major complication rate of 17-20%. In one study of 4000 infants with an umbilical artery catheter, 41 developed a major thromboembolic complication, an incidence of less than 1%. [11] The position of the umbilical artery catheters may affect the frequency of thromboembolic events. The tips of the catheters may be positioned high (ie, at the level of T5-10) or low (ie, at the level of L3-5). The optimal position for minimizing thromboembolism is uncertain.
Other complications of umbilical artery catheters include vasospasm, aortic thrombosis, partial or complete iliac artery thrombosis, and embolism to peripheral and visceral tissues.
Venous thrombosis is a common complication of vascular access in the pediatric population, with a reported incidence of up to 60%. [4, 5] In particular, central venous access devices (CVADs) have been identified as the biggest risk factor for this complication in children. Specific risk factors for thrombosis include catheter-to-vein ratio, catheter tip location, and catheter size. [6] Current clinical practice guidelines recommend a catheter-to-vein ratio of < 0.5 in children and < 0.33 in neonates. [5]
Femoral insertion sites have also been associated with an increased incidence of thrombotic complications as compared with subclavian vein access. [5] Furthermore, the formation of a fibrin sheath after insertion of a CVAD is thought to contribute to the risk of catheter-related thombosis. [4]
CVADs are associated with an overall complication rate of 42-80%, including mechanical (5-19%), infectious (5-26%), or thrombotic events (2-26%). Reported complications include infection, malpositioning, phlebitis, thrombosis, migration, pericardial or pleural effusion, chylothorax, peritoneal or retroperitoneal extravasation, cardiac arrhythmias, endocarditis, and pulmonary embolism. [4, 5] Mechanical complications include arterial puncture or laceration, 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 is sufficient to produce an air embolism in a child.
Risk factors for catheter-related mechanical complications included the following:
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Time needed for catheter insertion (number of needle passes) - More than three attempts were associated with a sixfold increase in the risk of a mechanical complication
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Insertion during the night (operator fatigue or inexperience) - Surgeons who placed more than 50 CVCs had a 50% decrease in the rate of complications
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Center effect
To reduce the risk of complicatons, clinical practice guidelines on vascular access in pediatric patients have recommended that all insertions be done under ultrasonographic (US) guidance. [5] This practice has decreased the number of attempts needed to cannulate the vein, as well as the incidence of iatrogenic injury. Placement of CVCs under fluoroscopic guidance allows for correct placement of the catheter and vein dilatation under direct vision.
Whereas percutaneous vascular access is favored in the pediatric population, iatrogenic vascular trauma may also result from complications involving wire retention or catheter fracture and migration. [4, 6] In most cases, vascular access is obtained means of the Seldinger technique; therefore, the risk of guide-wire retention is a common complication, occurring in as many as 11% of patients. [5] Fracture of catheters, though rare, may occur during device insertion or removal. [4, 6] With the evolution of endovascular techniques, early recognition of these complications is important after percutaneous interventions such as cardiac catheterization.
In children, cardiac catheterization has a complication rate of 4-8%. Complications include trapping of the angioplasty balloon, vascular tears, damage of the left pulmonary artery, mitral valve injury, coil migration, embolization, bleeding, and vascular laceration or perforation. A study involving 1674 paediatric cardiac catheterizations performed with a femoral approach demonstrated that surgical repair of iatrogenic femoral injuries occurred in 2% of patients, with an overall morbidity of 12% and mortality of 3%. [12] With advances in interventional catheterization, the use of large catheters and sheaths has increased the risk even further.
Prognosis
Serious complications, such as gangrene or limb loss, are rare. After arterial injury, fewer than one in 10 patients eventually progress to surgical revascularization; most symptoms resolve with conservative management. [4] However, delayed revascularization has been associated with poorer functional outcomes and limb-length discrepancy. [4] Moreover, children younger than 2 years have an increased risk of morbidity and mortality after iatrogenic vascular injury. [4]
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Right-hand gangrene and necrosis secondary to use of brachial artery catheter in very-low-birth-weight baby girl.
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Superior vena cava syndrome in patient with IV access device (Port-A-Cath) in right subclavian vein. Note facial and upper torso edema and prominent collateral veins.
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Close-up photograph of same patient with port incision and prominent collateral veins characteristic of superior vena cava syndrome secondary to catheter-related thrombotic complication.
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Six-month-old boy with severe superior vena cava syndrome after congenital cardiac surgery. Note severe facial, neck, and upper-chest swelling and distended superficial veins.
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Chest radiograph from same patient above, demonstrating soft-tissue swelling, lung infiltrates, and severely widened mediastinum. Central venous catheter is seen in place. Patient developed superior vena cava thrombosis secondary to central line.
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Caval venogram depicts considerable narrowing of infradiaphragmatic vena cava secondary to right hepatic trisegmentectomy. Patient developed mild inferior vena cava syndrome, was treated nonsurgically (with heparinization), and recovered adequately, developing collateral circulation without sequelae.
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Expanded polytetrafluoroethylene (e-PTFE) graft placed between right brachiocephalic trunk and right common carotid artery in 8-year-old boy with locally advanced medullary thyroid carcinoma, in which artery was resected en bloc with tumor. Neuroprotection was employed during anesthesia. Patient recovered uneventfully without neurologic problems. Graft was placed slightly long to accommodate growth.
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Screen showing internal jugular vein (arrow) and common carotid artery. Duplex blood flow and longitudinal view of internal jugular vein with needle inside (white arrow).
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Proposed algorithm in treatment of pediatric vascular injury. UH = Unfractionated heparin, rt-PA = recombinant-tissue plasminogen activator.
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Neonate boy with high supracondylar left lower limb amputation secondary to thrombosis of femoral artery with arterial line in place. Patient came to our department with signs of irreversible ischemia and extensive necrosis.
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Distal right-foot ischemia with fingertip gangrene in newborn baby girl with central venous catheter in right femoral vein, which, after multiple cannulation attempts with accidental arterial catheter placement, developed thrombus that migrated distally and produced ischemia and necrosis.
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Left-hand fingertip necrosis due to arterial line in brachial artery.
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Newborn baby boy with right femoral artery lesion during venous cutdown. Artery was surgically repaired. He postoperatively developed severe vasospasm and partial thrombosis, managed with thrombolytics. He had adequate Doppler signal and eventually recovered.