Pulmonary embolism with septicemia after N-butyl-2-cyanoacrylate injection for bleeding gastric varices

Despite many advances in the treatment of gastric variceal bleeding in the two past decades, its management continues to present a clinical challenge. Various treatment modalities have been proposed and since the first report in 1986 endoscopic injection sclerotherapy with cyanoacrylate tissue adhesives has become widely established in many countries as the treatment of choice for bleeding gastric varices. Severe complications of the treatment are infrequent, but when they occur may be lifethreatening. 1-4 We described a case of pulmonary embolism and septicemia after the endoscopic injection of N-butyl-2-cyanoacrylate. A 54-year-old woman with primary biliary cirrhosis and severe variceal bleeding was admitted to the hospital and treated with blood transfusion. The bleeding ceased spontaneously. Endoscopy disclosed giant isolated fundic varices (IGV1) and the decision was made to obliterate them with cyanoacrylate glue to prevent rebleeding. Obliteration was performed using a mixture of 0.5 ml N-butyl-2-cyanoacrylate (Histoacryl, Braun Surgical, Melsungen, Germany) and 0.8 ml Lipiodol (Guerbet, Aulney-sous-Bois, France). One milliliter of the mixture was used per injection with a total of 12 ml of Histoacryl-Lipiodol mixture injected during the procedure to achieve a total obliteration. Two days after the procedure the patient developed fever (39°C), chills and hypotension accompanied by severe pancytopenia. A plain chest radiograph (Figure 1A) showed opacifications in the right upper lobe and linear opacities in the right hilum. On chest CT scan embolized hyperdense glue material was shown predominantly in the pulmonary arteries of the right upper lobe and there were radioopacities suggesting pulmonary infarction (Figure 1B). Collateral circulation through a large spontaneous splenorenal shunt which contained the glue material was seen on abdominal CT scans indicating the pathway of systemic glue embolization (Figure 1C). Staphylococcal sepsis and right lobar pneumonia were diagnosed and treated with several antibiotics (amoxycillin, ceftriaxone, meropenem, vancomycin, ciprofloxacin, teicoplanin, amikacin and clarithromycin). The patient's condition improved and she was discharged home after 5 weeks of hospitalization. However, 6 weeks later she had to be readmitted to the hospital because of recurrent fever, chills, diarrhea, hypotension, and dyspnoea.Figure 1.: Plain chest radiograph showing opacifications in the right upper lobe (arrowhead) and in the in the right hilum (arrows), the latter suggesting embolized material in the pulmonary vessels (A); Chest CT scan showing embolized Histoacryl-Lipiodol mixture in the segmental artery of the right upper lobe (arrow) and radiopacities suggestive of pulmonary infarction (arrowhead) (B); Abdominal CT scan presenting hyperdense material in a large splenorenal shunt (Histoacryl-Lipiodol mixture) (arrow) (C); Abdominal CT scan showing a large amount of Histoacryl-Lipiodol mixture in the stomach fundus (arrow), with inflammatory reaction in the gastric wall (arrowheads) (D).No signs of inflammation were found on chest radiograph. However, a plain abdominal radiograph showed a radioopaque shadow in the left upper abdomen and an abdominal CT scan showed a foreign body identified as composed of cyanoacrylate in the gastric fundus with an inflammatory reaction in the gastric wall (Figure 1D). The patient was again treated with several different antibiotics (meropenem, amikacin, teicoplanin, ciprofloxacin, cefoperazone and sulbactam). When blood cultures identified Serratia species she was treated with imipenem and cilasplatin for 16 days. The fever subsided and the patient was discharged after 40 days of hospitalization. A follow-up CT scan showed no signs of gastric fundic inflammation. Since then no recurrence of the complications and no bleeding have been observed. Gastric variceal bleeding is a life-threatening complication of portal hypertension. It occurs less frequently than esophageal variceal bleeding, but is usually massive with a more abundant blood flow and hence more difficult to control. The varices are fed by the short gastric and posterior gastric veins and drain into left renal vein via a large gastrorenal or splenorenal shunt.3 The tissue glue N-butyl-2-cyanoacrylate is considered by many to be the treatment of choice for gastric variceal bleeding.1-4 It has been shown to be superior to other endoscopic techniques such as sclerotherapy and band ligations.1-4 The main problem with this technique is the occurrence of sporadic systemic embolic complications, which seem to occur most commonly through a large splenorenal shunt.3 Glue embolization has been described at different organs such as brain, portal vein, spleen, and lungs with the lungs being the most common site of systemic embolization. The pulmonary embolic complications range in severity from asymptomatic and mild to fatal. The lungs stop most of the embolic material, but embolization to different sites can occur through the pulmonary arteriovenous malformations or via the patent foramen ovale or an atrial septal defect.2 Our patient suffered near fatal multiple pulmonary embolism with septicemia. The embolic glue material in the lungs was documented on plain chest radiographs and CT scans. The glue material dispersed through a spontaneous splenorenal shunt into the inferior vena cava resulted in pulmonary embolism. The risk factors of glue embolization can be patient- or technique-related. Large gastric varices associated with large gastrorenal or splenorenal shunts and high variceal blood flow increase the risk of distal embolization.2 The presence of pulmonary arteriovenous malformations or an atrial septal defect is another risk factor of embolization to different organs.2 Technique-related factors include the volume of the injection, total volume injected, dilution of the glue and the speed of injection. N-butyl-2-cyanoacrylate hardens within four seconds on contact with blood.2 Dilution with a contrast medium (Lipiodol or ethidiol) is used to prevent immediate polymerization.2 Cases of sticking of the needle to the varix have been reported when undiluted N-butyl-2-cyanoacrylate was injected.2,4 Dilution of the glue allows radiologic monitoring of the injection as well as assessment of completeness of varix obliteration. However, overdilution increases the risk of systemic embolization because the resulting delayed glue polymerization may lead to dispersing of the glue particles into the systemic circulation before the glue solidifies.2 Different concentrations of the glue mixed with Lipiodol have been used. An expert panel consensus proposed the optimal proportions of for the Histoacyrl-Lipiodol mixture of either 0.5 ml to 0.8ml2 or 1: 1.3,4 To minimize the risk of embolization not more than 1.0 ml of the mixture should be injected at a time and in the case of large gastric varices, the injections have be repeated.2 The speed of injection of the glue may be another risk factor.2 It has been shown in an experimental study by Suga et al, that a slow injection speed is a factor contributing to fragmentation of the glue and embolization.5 If the injection is slow and the variceal blood flow high, as is the case in large gastric varices, migration of the glue is possible.5 In addition to the embolic complications our patient suffered from multiple episodes of severe sepsis. Similar septic complications have been reported by other authors.3,4 The source of bacteremia in our patient is difficult to ascertain. It seems, however, that she may have suffered septic complications due to the bacterial contamination of the glue material in the gastric fundus, which represented the communication between the gastric lumen and the vascular system. The infection recurred despite treatment with different antibiotics and and it could be successfully controlled only after the extrusion of the glue conglomerate. A similar outcome has been reported by other authors.4 In conclusion, we believe that the large amount of the glue injected during one session was the main cause of the complications. We think that in patients with very large gastric varices when a high blood flow is expected and a large splenorenal shunt is often present either the concentration of the injected glue should be increased or the alternative treatment methods such as Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) should be considered.3