Background
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 represent 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 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, 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.
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. Currently, aggressive surgical management yields better results, making early diagnosis and 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 vascular injuries are needed. With the advent of newer technology and the clinical possibilities that it offers, the management of pediatric vascular 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. Children have small vessels in compact anatomic spaces and frequently require large catheters. It has been shown that catheters with a diameter exceeding 50% of the arterial diameter result in spasm and low flow rates, making them prone to thrombosis. [2]
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
The usual sequence begins with arterial puncture, which is followed by spasm and thrombotic occlusion. The vascular endothelium has a predominant role in blood coagulation and has numerous interactions with perivascular cells and adjacent tissues. 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, resulting in a prothrombotic state. Apparently, pediatric vessels are hyperreactive, producing severe and persistent vasospasm.
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. [4] 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 lesions associated with use of the femoral approach can be divided into two broad categories, ischemic and nonischemic; the former category can be further subdivided into acute and chronic. Acute ischemia occurs in 41.2% of patients, whereas chronic ischemia is reported in 20.6%. Nonischemic injuries include pseudoaneurysms, arteriovenous fistulas, 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.
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.
Pediatric iatrogenic vascular lesions are secondary to arteriography, cardiac catheterism, arterial puncture, repeated blood samples, vascular access, or foreign bodies (eg, fractured or displaced guide wires 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. 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 lesions largely result from orthopedic procedures and tumor resections done by surgical oncologists, who frequently perform large dissections in areas with distorted anatomy where the planes of dissection are usually lost and with large blood vessels involved in the tumor. 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 tumors 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. [5, 6] The interventional radiologist plays a key role in the management of such lesions because most can be successfully treated endovascularly.
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 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 due to transfemoral cardiac catheterization are in the range of 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 one study of 4000 infants with an umbilical artery catheter, 41 developed a major thromboembolic complication, an incidence of less than 1%. [7] Arterial complications of umbilical artery catheters include vasospasm, aortic thrombosis, partial or complete iliac artery thrombosis, and embolism to peripheral and visceral tissues.
The position of the umbilical artery catheters may affect the frequency of thromboembolic events. The tips of umbilical artery 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 remains uncertain.
AVFs secondary to multiple arterial punctures in neonates are rare.
Age and size are important risk factors for arterial injuries. Infants weighting 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 the neonatal intensive care unit (NICU) in 1987-1994 demonstrated a higher risk of iatrogenic vascular injuries in neonates with extremely low or low birth weight (2.6%) as compared with older or heavier neonates (0.3%). [8]
Different types of catheters used in the pediatric age group have specific associated complications.
CVCs can lead to serious and sometimes life-threatening complications. CVCs are associated with an overall complication rate of 42-80%, including mechanical (5-19%), infectious (5-26%), or thrombotic events (2-26%). The choice of insertion site can influence the incidence and type of complication. The coagulation cascade is activated by the mere presence of a catheter in the vein, which provokes physical 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 in place. [9] Complications reported with these vascular devices include infection, incorrect placement, phlebitis, vascular dissection and tears, hemothorax, pneumothorax, thrombosis, migration, pericardial or pleural effusion, chylothorax, peritoneal or retroperitoneal extravasation, cardiac arrhythmias, endocarditis, and pulmonary embolism.
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. Most international guidelines for vascular access in pediatric patients currently recommend all insertions to be done under ultrasonographic guidance. This 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.
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. [10] 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
The femoral site has a fivefold hgiher incidence of catheter-related infectious complications than the subclavian approach. This risk can be reduced with the use of subcutaneous tunneling, antibiotic-impregnated catheters, and the administration of systemic antibiotics through the catheter.
The femoral approach also has an increased incidence of thrombotic complications (21%) as compared with the subclavian catheters (1.9%). Some studies have shown that subclavian catheterization should be preferred over 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 higher 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 et al reported on 1674 pediatric cardiac catheterizations performed with a femoral approach. [11] Iatrogenic inguinal lesions that required surgical repair occurred in 2%, with an overall morbidity of 12% and a mortality of 3%.
Finally, with advances in interventional catheterization, the use of large catheters and sheaths increase the risk even further.
Prognosis
Serious complications, such as gangrene or limb loss, are rare. However, approximately 10% of children develop vascular symptoms or limb-length discrepancy. Therefore, limb length should be monitored, and surgery should be performed if a discrepancy is found before the adolescent growth spurt occurs.
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Right-hand gangrene and necrosis secondary to use of a brachial-artery catheter in very-low-birth-weight baby girl.
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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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Close-up photograph 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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A 6-month-old boy with severe superior vena cava syndrome after congenital cardiac surgery. Note the severe facial, neck, and upper-chest swelling and distended superficial veins.
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Chest radiograph from the same patient above. It demonstrates soft tissue swelling, lung infiltrates, and a severely widened mediastinum. A central venous catheter is seen in place. The patient developed a superior vena cava thrombosis secondary to the central line.
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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.
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An expanded polytetrafluoroethylene (e-PTFE) graft placed between the right brachyocephalic trunk and the right common carotid artery in a 8-year-old boy with locally advanced medullary thyroid carcinoma, in which the artery was resected en-block with the tumor. Neuroprotection was employed during anesthesia. The patient recovered uneventfully without neurologic problems. The graft was placed slightly long to accommodate for growth.
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Screen showing the internal jugular vein (arrow) and common carotid artery. Duplex blood flow and longitudinal view of the internal jugular vein with needle inside (white arrow).
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Proposed algorithm in the treatment of pediatric vascular injury. UH = Unfractionated heparin, rt-PA = recombinant-tissue plasminogen activator.
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Neonate boy with a high supracondilear left lower limb amputation secondary to thrombosis of the femoral artery while having an arterial line in place. Patient came to our department with signs of irreversible ischemia and extensive necrosis.
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Neonate boy with a high supracondilear left lower limb amputation secondary to thrombosis of the femoral artery while having an 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 fingertips gangrene in a newborn babygirl with a central venous catheter in ther right femoral vein, which after multiple canulation atempts with accidental arterial catheter placement, developed a thrombus that migrated distaly and produced ischemia and necrosis.
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Left hand finger tips necrosis due to an arterial line in the brachial artery.
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Newborn baby boy with a right femoral artery lesion during a 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.