- Email: [email protected]
Laparoscopic repair of inferior vena caval injury using a chitosan-based hemostatic dressing
The American Journal of Surgery (2009) 197, 510 –514
Scientific (Exp)/Research
Laparoscopic repair of inferior vena caval injury using a chitosan-based hemostatic dressing Hua Xie, M.D., Ph.D.a,*, Jeffrey S. Teach, R.N.a, Allen P. Burke, M.D.b, Lisa D. Lucchesi, M.S.a, Ping-Cheng Wu, M.S.a, Rebecca C. Sarao, B.S.a a
Oregon Medical Laser Center, Providence St. Vincent Medical Center, 9205 SW Barnes Rd., Portland, OR 97225, USA; Shady Grove Adventist Hospital, Rockville, MD, USA
b
KEYWORDS: Laparoscopic; Inferior vena cava; Injury; Animal model
Abstract BACKGROUND: Vena caval injury is a rare but serious complication of laparoscopic surgery, and often requires conversion to an open procedure. The current study investigated whether a vena caval injury could be repaired with a chitosan dressing laparoscopically. METHODS: Six domestic swine were studied. A 4- to 5-mm circumferential incision was created in the inferior vena cava (IVC) and repaired laparoscopically with a chitosan dressing. Neither suture nor additional hemostatic techniques were used. The animals were killed at 30 minutes (n ⫽ 2) and at 1 week (n ⫽ 4) postoperatively for histopathological analysis. RESULTS: All IVC injuries were successfully repaired laparoscopically using a single chitosan dressing application without recurrent hemorrhaging. Mean operative time was 6 minutes and the blood loss was approximately 55 mL. There was no evidence of clot formation in the repaired vessels. Histology showed that the chitosan dressing had partially degenerated into small particles with moderate chronic inflammatory response 1 week after repair. CONCLUSION: Use of the chitosan-based hemostatic dressing is a simple and reliable technique to control serious hemorrhage from IVC injury during laparoscopic surgery. © 2009 Published by Elsevier Inc.
Major vascular injuries during laparoscopic surgery are rare but potentially life-threatening. Reported incidences range from .01% to 1.98% depending on the surgical field and approach.1–3 The incidence of venous dissection injuries is approximately 1.7% for laparoscopic urological procedures.4 Management of vascular injuries during laparoscopic procedure is critical and often requires conversion to an open surgical technique. Occasionally, a venous dissec-
This work was supported by a US Army research grant (DAMD 17-02-C-0095). * Corresponding author. Tel.: ⫹1-503-216-6826; fax: ⫹1-503-216-5256. E-mail address: [email protected] Manuscript received August 29, 2007; revised manuscript December 19, 2007
0002-9610/$ - see front matter © 2009 Published by Elsevier Inc. doi:10.1016/j.amjsurg.2007.12.050
tion injury may be repaired laparoscopically, but it is a time-consuming and highly technical procedure. A chitosan-based hemostatic dressing (HemCon Medical Technologies Inc, Portland, OR) has been shown to effectively control aggressive hemorrhaging from severe combat traumatic injuries.5 Previous studies demonstrated a prototype of the chitosan dressing significantly reduced mortality, blood loss, and resuscitative fluid requirements in severe arterial, venous, and hepatic injury models.6,7 A new bioabsorbable chitosan dressing has been produced that consists of a highly purified chitosan with an impermeable, bioabsorbable and flexible backing. This dressing was designed as an implantable topical hemostatic dressing to control severe bleeding during surgery. In our laboratory, the bio-absorbable chitosan dressing was used successfully to control renal parenchymal hemor-
H. Xie et al.
Laparoscopic IVC injury repair using chitosan
rhage in laparoscopic partial nephrectomy.8 In the current study, we evaluated the laparoscopic use of the bioabsorbable chitosan dressing for controlling severe inferior vena cava (IVC) hemorrhage.
511 Table 1
Hemorrhage scale
Grade
Definition
Findings
0
Brisk steady bleeding
1
Moderate bleeding/ oozing
2
Mild oozing
3
Dry/no bleeding
Life-threatening arterial or vigorous venous bleeding Persistent bleeding from wound area requiring a supplemental coagulation technique Bleeding anticipated to stop on its own or by applying pressure No active bleeding
Materials and Methods The chitosan dressings were prepared using dilute aqueous acetic acid solutions of ultrapure grades of chitosan. After freeze-drying, the chitosan matrix was compressed, annealed, and gamma-irradiated to produce sterile, dissolution-resistant, and adhesive dressings. The chitosan dressings were 58 mm in diameter and ranged from 1.5 to 1.85 mm thick. The chitosan density ranged from .12 and .15 g/cm3. A thin compliant bioabsorbable polymer film (TephaFLEX polymer; Tepha Inc, Lexington, MA) was placed on one side as a waterproof backing. This film reinforced the dressing and reduced adhesion to the surgical instruments.8 The backing side faces up when applying and the active side is the side directly applied to the wound surface. Six crossbred adult domestic swine of mixed gender and body weight (57 ⫾ 11 kg) were studied. All procedures for handling and caring for the animals were performed in accordance with the 1996 National Research Council’s “Guide for the Care and Use of Laboratory Animals,” and approved by the Institutional Animal Care and Use Committee of our research institution. After induction of general anesthesia, the animal was placed in a right lateral position and draped sterilely. CO2 pneumoperitoneum was established to 15 mm Hg through a 14-gauge Veress needle. Four working ports were placed: (1) a 5-mm port was placed on the right midaxillary line 3 inches above umbilicus; (2) a 5-mm port was placed 1 inch below the umbilicus and 7 inches away from the first port in the right lower quadrant; (3) a 10-mm camera port was placed on the right midclavicular line 2 inches above the umbilicus; and (4) a 10-mm port was placed at midway between the first and the third ports for the introduction of the chitosan dressing and a fan retractor. The IVC was exposed by retracting small bowel and pancreatic glandular tissue. A 4- to 5-mm circumferential incision injury in the IVC was created using sharp scissors at the anterior wall of the suprarenal section close to the junction of right renal vein. After the IVC injury, a preoperative hemorrhage score was assessed visually using the 4-grade scale in Table 1.9 The bleeding was then temporarily controlled using an atraumatic vascular clamp. Immediately after the vascular clamp was released, a chitosan dressing (58 mm diameter) was furled and delivered through a 10-mm port. The dressing was unfurled and deployed onto the IVC injury site with gentle compression using a 5-mm fan retractor (US Surgical, Norwalk, CT) for 3 minutes. After completion of the 3 minutes of compression, the hemorrhage score was reassessed. If hemostasis
Modified hemorrhage scale system of Jackman et al.9
was satisfactory (hemorrhage score ⫽ 3), the abdomen was deflated and observed for 30 additional minutes. If hemostasis was incomplete (hemorrhage score ⱕ2), the chitosan dressing was removed and a second dressing was deployed as described above. The number of attempts required for success and total operative time were recorded. The volume of blood loss was estimated by intraperitoneal aspiration. Once complete hemostasis was confirmed laparoscopically for 30 minutes, the skin incisions were closed in a 2-layer fashion. Two animals were taken to fluoroscopy for venography and then euthanized after the procedure. Four animals were allowed to recover from anesthesia and were returned to their pen for 1 week. The animal status was monitored daily by veterinary staff. Possible postoperative bleeding was assessed by clinical observation and hemoglobin and hematocrit measurements. On postoperative day 7, laparoscopy and venography were performed under general anesthesia. These animals were then euthanized and the IVC specimen was collected for histological analysis. Routine hematoxylin and eosin and Movat pentachrome stains were made on paraffin-embedded sections containing the IVC and residual chitosan dressing.
Results All laparoscopic procedures were successful. In all cases, hemostasis was achieved with a single application of the chitosan dressing. The surgical field was dry following application of the chitosan dressing on the injury site. The animals survived without any evidence of immediate or delayed hemorrhage. The 4 chronic animals behaved normally and had no signs of postoperative infection, bowel obstruction, or other complications. The mean repair time of the IVC injuries was 6 ⫾ 3 minutes. This included the time needed to create the injury, control the bleeding with a vascular clamp, furl the chitosan dressing for deployment, deliver the dressing, and hold for 3 minutes. The mean estimated blood loss was 55 ⫾ 54 mL (range 10 to 143 mL). No sutures, clips, or additional hemostatic agents were used
512 Table 2
The American Journal of Surgery, Vol 197, No 4, April 2009 Blood laboratory information of chronic study Postoperative P Preoperative day 7 value*
Body weight WBC Neutrophil Lymphocyte Monocyte Eosinophil RBC HGB HCT MCV MCH MCHC
(kg) (x103/L) (%) (%) (%) (%) (x106/L) (g/dL) (%) (fL) (pg) (g/dL)
57 16.9 38 57 2 2 5.7 10 29.7 52.7 17.7 33.5
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
11 2.4 13 14 .6 1.7 1.2 1.2 3.2 4.9 1.5 .8
59 15.9 41 54 4 2 4.9 8.6 26.4 54.8 17.8 32.6
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
17 2.6 9 8 1 1.5 .5 .5 1.6 4 1.3 1
.6 .6 .8 .7 .1 .9 .4 .2 .2 .6 .9 .2
WBC ⫽ white blood cell count; RBC ⫽ red blood cell count; HGB ⫽ hemoglobin; HCT ⫽ hematocrit; MCV ⫽ mean cell volume; MCH ⫽ mean cell hemoglobin; MCHC ⫽ mean cell hemoglobin concentration. *Comparison between preoperative and postoperative with t test.
during the operation. The chitosan dressing was easily applied and held in place by using a laparoscopic fan-retractor. Venographic imaging showed no clot formation in the injured vessels. No significant postoperative decline in hematocrit and hemoglobin levels was seen in the chronic animals (Table 2). There was no clinical evidence of rebleeding,
such as hematoma or sanguineous ascites. The chitosan dressing was observed to be adherent to the IVC injury site at necropsy. Microscopic examination of the repaired IVC revealed that the chitosan was partially degenerated into small particles, which elicited the moderate chronic inflammation with granulation tissue. The particles were both extracellular and intracellular, the smaller ones (10 –100 m) within the cytoplasm of foreign body macrophages (Figure 1). There was no accumulated clot in the vessel lumen.
Comments The incidence of iatrogenic vena caval injury is very low but has been reported for a variety of laparoscopic surgical procedures.10 –13 Laparoscopic repair of vena caval injury sometimes can be troublesome due to limited exposure and poor visibility. It is highly recommended to convert to an open procedure if a vena caval injury has occurred. Nazhat et al reported 2 cases of IVC injury during pelvic and para-aortic node dissection in gynecological procedures.13 These injuries were repaired with an immediate laparotomy or a laparoscopic procedure. The laparotomy patient lost a significant amount of blood after removal of pneumoperitoneum pressure and required transfusion of 4 units of packed
Figure 1 (Top left) Gross image shows perforation injury site (marked by arrow) on the intimal surface of the IVC. (Top right) Low magnification image shows that the chitosan (C) dressing material has been incorporated into adventitia side of the IVC wall with moderate chronic inflammation (original magnification 25⫻, Movat pentachrome stain). (Bottom left) Higher magnification image shows that chitosan material (C) was broken down into small spherules, surrounded by inflammatory cells, primarily macrophages and lymphocytes. (Bottom right) Small chitosan spherules (⬃15–100 m, marked by arrow heads) engulfed by macrophages and multinucleated macrophages are visible (original magnification 400⫻, Movat pentachrome stain).
H. Xie et al.
Laparoscopic IVC injury repair using chitosan
red blood cells. An earlier national survey found that vascular injuries occurred in .25% of laparoscopic cholectectomy cases.1 Usal et al reported a total of 3 major vascular injuries among 2,589 laparoscopic cholectectomy procedures. These injuries involved the portal vein, aorta, and vena cava, and were repaired by exploratory laparotomy.14 Major vascular complications occur with an incidence of 1.98% in urological procedures.3 Thiel et al reported 4 cases of IVC injury during a right radical nephrectomy. These injuries were treated using laparoscopic vascular suturing techniques and were accompanied by a an average blood loss of 980 mL.4 The authors concluded that injury to the fragile vena cava can be managed laparoscopically by surgeons with extensive laparoscopic experience. In particular, surgeons must be meticulous during intracorporeal suturing.4 The external chitosan dressing is a hemostatic agent approved by the US Food and Drug Administration (FDA) for emergency treatment of severe hemorrhage to surface wounds. This chitosan dressing has demonstrated efficacy for a variety of traumatic injuries.5 The hemostatic action of chitosan is believed to be achieved through a combination of wound sealing and the promotion of local clot formation by erythrocyte agglutination and platelet activation.5,7 The dressings used in previous studies were a 100 ⫻ 100 ⫻ 2-mm thick square dressing with nonabsorbable polyethylene backing.5 The chitosan dressing in this study replaced the nonabsorbable backing with a bioabsorbable thin film. The current dressing is designed to provide enhanced compliance and bioabsorbability, as well as more uniform tissue adhesion and good resistance to dissolution in blood. In this study, the bioabsorbable chitosan dressing was immediately effective and provided reliable hemostasis to the vena caval injury. This chitosan dressing is easy to use laparoscopically because the chitosan immediately adheres to tissue. All of the IVC injuries were repaired with a single chitosan dressing application and no repairs exhibited any delayed bleeding. No postoperative infection or venous thrombosis was observed. Histological examination of the repaired IVC and surrounding tissue revealed no evidence of biological incompatibility. Compared to currently available topical hemostatic methods, the bioabsorbable chitosan dressing has several advantages. The chitosan dressing provides a convenient and rapid method to control bleeding by adhesively sealing the wound site. Use of the chitosan dressing can simplify the laparoscopic vascular repair procedure and save time when a vascular injury occurs. Clinically significant uses of the chitosan dressing in laparoscopic surgery are numerous. The chitosan dressing can be used to control bleeding from vena caval injury but also for bleeding from visceral organs after routine biopsy and resection, laparoscopic portal bleeding, or fluid leakage from injured organs. There are several limitations to this experimental study. Currently, the chitosan dressing is only approved by the FDA for external use and it must be removed after initial
513 application. However, emergency use of the dressing may provide time for the surgeon to plan a rescue strategy or to perform the operation. Another concern is that our porcine model had very little retroperitoneal fat compared to humans; therefore, exposure of an IVC injury in humans may be more difficult and the chitosan dressing may not be effective on fatty tissue. Finally, this study had no control group because no IVC injury can be treated with a topical hemostatic agent alone at the present time. Although the IVC injury was created with a significant fatal IVC bleeding, the fate of untreated animals (or animals treated with gauze sponge compression alone) is unknown in the current model. The chitosan dressing should also be evaluated in a long-term biocompatibility study before human use.
Conclusions Our study results indicate that vena caval injury can be repaired laparoscopically with a bioabsorbable chitosanbased hemostatic dressing. Application of the chitosan dressing is not technically demanding and immediately seals the wound. This technique has the potential for achieving laparoscopic control of hemorrhage from solid organs as a result of surgical injury or following trauma. Further long-term studies should be performed prior to human clinical trials.
Acknowledgment The authors would like to express their gratitude to Ky Dehlinger, D.V.M., and Teresa Malarkey of the Legacy Clinical Research and Technology Center for assistance in the animal surgeries and postoperative care.
References 1. Deziel DJ, Millikan KW, Economou SG, et al. Complications of laparoscopic cholecystectomy: a national survey of 4,292 hospitals and an analysis of 77,604 cases. Am J Surg 1993;165:9 –14. 2. Harkki-Siren P, Kurki T. A nationwide analysis of laparoscopic complications. Obstet Gynecol 1997;89:108 –12. 3. Permpongkosol S, Link RE, Su LM, et al. Complications of 2,775 urological laparoscopic procedures: 1993 to 2005. J Urol 2007;177: 580 –5. 4. Thiel R, Adams JB, Schulam PG, et al. Venous dissection injuries during laparoscopic urological surgery. J Urol 1996;155:1874 – 6. 5. Wedmore I, McManus JG, Pusateri AE, et al. A special report on the chitosan-based hemostatic dressing: experience in current combat operations. J Trauma 2006;60:655– 8. 6. Kheirabadi BS, Acheson EM, Deguzman R, et al. Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in Swine. J Trauma 2005;59:25–34. 7. Pusateri AE MS, Gregory KW, Harris RA, et al. Effect of a chitosanbased hemostatic dressing on blood loss and survival in a model of severe venous hemorrhage and hepatic injury in swine. J Trauma 2003;54:177– 8.
514 8. Xie H, Khajanchee YS, Shaffer BS. Chitosan hemostatic dressing for renal parenchymal wound sealing in porcine model: implications for technique of laparoscopic partial nephrectomy. J Soc Laparoendosc Surg 2008;12:18-29. 9. Jackman SV, Cadeddu JA, Chen RN, et al. Utility of the harmonic scalpel for laparoscopic partial nephrectomy. J Endourol 1998;12:441– 4. 10. Battaglia L, Bartolucci R, Berni A, et al. Major vessel injuries during laparoscopic cholecystectomy: a case report. Chir Ital 2003;55:291– 4. 11. Carlson MA, Frantzides CT. Control of venous hemorrhage during laparoscopic adrenalectomy: a case report. J Laparoendosc Surg 1996;6:349–51.
The American Journal of Surgery, Vol 197, No 4, April 2009 12. McAllister M, Bhayani SB, Ong A, et al. Vena caval transection during retroperitoneoscopic nephrectomy: report of the complication and review of the literature. J Urol 2004;172:183–5. 13. Nezhat C, Childers J, Nezhat F, et al. Major retroperitoneal vascular injury during laparoscopic surgery. Hum Reprod 1997;12: 480 –3. 14. Usal H, Sayad P, Hayek N, et al. Major vascular injuries during laparoscopic cholecystectomy. An institutional review of experience with 2589 procedures and literature review. Surg Endosc 1998;12: 960 –2.
Scientific (Exp)/Research
Laparoscopic repair of inferior vena caval injury using a chitosan-based hemostatic dressing Hua Xie, M.D., Ph.D.a,*, Jeffrey S. Teach, R.N.a, Allen P. Burke, M.D.b, Lisa D. Lucchesi, M.S.a, Ping-Cheng Wu, M.S.a, Rebecca C. Sarao, B.S.a a
Oregon Medical Laser Center, Providence St. Vincent Medical Center, 9205 SW Barnes Rd., Portland, OR 97225, USA; Shady Grove Adventist Hospital, Rockville, MD, USA
b
KEYWORDS: Laparoscopic; Inferior vena cava; Injury; Animal model
Abstract BACKGROUND: Vena caval injury is a rare but serious complication of laparoscopic surgery, and often requires conversion to an open procedure. The current study investigated whether a vena caval injury could be repaired with a chitosan dressing laparoscopically. METHODS: Six domestic swine were studied. A 4- to 5-mm circumferential incision was created in the inferior vena cava (IVC) and repaired laparoscopically with a chitosan dressing. Neither suture nor additional hemostatic techniques were used. The animals were killed at 30 minutes (n ⫽ 2) and at 1 week (n ⫽ 4) postoperatively for histopathological analysis. RESULTS: All IVC injuries were successfully repaired laparoscopically using a single chitosan dressing application without recurrent hemorrhaging. Mean operative time was 6 minutes and the blood loss was approximately 55 mL. There was no evidence of clot formation in the repaired vessels. Histology showed that the chitosan dressing had partially degenerated into small particles with moderate chronic inflammatory response 1 week after repair. CONCLUSION: Use of the chitosan-based hemostatic dressing is a simple and reliable technique to control serious hemorrhage from IVC injury during laparoscopic surgery. © 2009 Published by Elsevier Inc.
Major vascular injuries during laparoscopic surgery are rare but potentially life-threatening. Reported incidences range from .01% to 1.98% depending on the surgical field and approach.1–3 The incidence of venous dissection injuries is approximately 1.7% for laparoscopic urological procedures.4 Management of vascular injuries during laparoscopic procedure is critical and often requires conversion to an open surgical technique. Occasionally, a venous dissec-
This work was supported by a US Army research grant (DAMD 17-02-C-0095). * Corresponding author. Tel.: ⫹1-503-216-6826; fax: ⫹1-503-216-5256. E-mail address: [email protected] Manuscript received August 29, 2007; revised manuscript December 19, 2007
0002-9610/$ - see front matter © 2009 Published by Elsevier Inc. doi:10.1016/j.amjsurg.2007.12.050
tion injury may be repaired laparoscopically, but it is a time-consuming and highly technical procedure. A chitosan-based hemostatic dressing (HemCon Medical Technologies Inc, Portland, OR) has been shown to effectively control aggressive hemorrhaging from severe combat traumatic injuries.5 Previous studies demonstrated a prototype of the chitosan dressing significantly reduced mortality, blood loss, and resuscitative fluid requirements in severe arterial, venous, and hepatic injury models.6,7 A new bioabsorbable chitosan dressing has been produced that consists of a highly purified chitosan with an impermeable, bioabsorbable and flexible backing. This dressing was designed as an implantable topical hemostatic dressing to control severe bleeding during surgery. In our laboratory, the bio-absorbable chitosan dressing was used successfully to control renal parenchymal hemor-
H. Xie et al.
Laparoscopic IVC injury repair using chitosan
rhage in laparoscopic partial nephrectomy.8 In the current study, we evaluated the laparoscopic use of the bioabsorbable chitosan dressing for controlling severe inferior vena cava (IVC) hemorrhage.
511 Table 1
Hemorrhage scale
Grade
Definition
Findings
0
Brisk steady bleeding
1
Moderate bleeding/ oozing
2
Mild oozing
3
Dry/no bleeding
Life-threatening arterial or vigorous venous bleeding Persistent bleeding from wound area requiring a supplemental coagulation technique Bleeding anticipated to stop on its own or by applying pressure No active bleeding
Materials and Methods The chitosan dressings were prepared using dilute aqueous acetic acid solutions of ultrapure grades of chitosan. After freeze-drying, the chitosan matrix was compressed, annealed, and gamma-irradiated to produce sterile, dissolution-resistant, and adhesive dressings. The chitosan dressings were 58 mm in diameter and ranged from 1.5 to 1.85 mm thick. The chitosan density ranged from .12 and .15 g/cm3. A thin compliant bioabsorbable polymer film (TephaFLEX polymer; Tepha Inc, Lexington, MA) was placed on one side as a waterproof backing. This film reinforced the dressing and reduced adhesion to the surgical instruments.8 The backing side faces up when applying and the active side is the side directly applied to the wound surface. Six crossbred adult domestic swine of mixed gender and body weight (57 ⫾ 11 kg) were studied. All procedures for handling and caring for the animals were performed in accordance with the 1996 National Research Council’s “Guide for the Care and Use of Laboratory Animals,” and approved by the Institutional Animal Care and Use Committee of our research institution. After induction of general anesthesia, the animal was placed in a right lateral position and draped sterilely. CO2 pneumoperitoneum was established to 15 mm Hg through a 14-gauge Veress needle. Four working ports were placed: (1) a 5-mm port was placed on the right midaxillary line 3 inches above umbilicus; (2) a 5-mm port was placed 1 inch below the umbilicus and 7 inches away from the first port in the right lower quadrant; (3) a 10-mm camera port was placed on the right midclavicular line 2 inches above the umbilicus; and (4) a 10-mm port was placed at midway between the first and the third ports for the introduction of the chitosan dressing and a fan retractor. The IVC was exposed by retracting small bowel and pancreatic glandular tissue. A 4- to 5-mm circumferential incision injury in the IVC was created using sharp scissors at the anterior wall of the suprarenal section close to the junction of right renal vein. After the IVC injury, a preoperative hemorrhage score was assessed visually using the 4-grade scale in Table 1.9 The bleeding was then temporarily controlled using an atraumatic vascular clamp. Immediately after the vascular clamp was released, a chitosan dressing (58 mm diameter) was furled and delivered through a 10-mm port. The dressing was unfurled and deployed onto the IVC injury site with gentle compression using a 5-mm fan retractor (US Surgical, Norwalk, CT) for 3 minutes. After completion of the 3 minutes of compression, the hemorrhage score was reassessed. If hemostasis
Modified hemorrhage scale system of Jackman et al.9
was satisfactory (hemorrhage score ⫽ 3), the abdomen was deflated and observed for 30 additional minutes. If hemostasis was incomplete (hemorrhage score ⱕ2), the chitosan dressing was removed and a second dressing was deployed as described above. The number of attempts required for success and total operative time were recorded. The volume of blood loss was estimated by intraperitoneal aspiration. Once complete hemostasis was confirmed laparoscopically for 30 minutes, the skin incisions were closed in a 2-layer fashion. Two animals were taken to fluoroscopy for venography and then euthanized after the procedure. Four animals were allowed to recover from anesthesia and were returned to their pen for 1 week. The animal status was monitored daily by veterinary staff. Possible postoperative bleeding was assessed by clinical observation and hemoglobin and hematocrit measurements. On postoperative day 7, laparoscopy and venography were performed under general anesthesia. These animals were then euthanized and the IVC specimen was collected for histological analysis. Routine hematoxylin and eosin and Movat pentachrome stains were made on paraffin-embedded sections containing the IVC and residual chitosan dressing.
Results All laparoscopic procedures were successful. In all cases, hemostasis was achieved with a single application of the chitosan dressing. The surgical field was dry following application of the chitosan dressing on the injury site. The animals survived without any evidence of immediate or delayed hemorrhage. The 4 chronic animals behaved normally and had no signs of postoperative infection, bowel obstruction, or other complications. The mean repair time of the IVC injuries was 6 ⫾ 3 minutes. This included the time needed to create the injury, control the bleeding with a vascular clamp, furl the chitosan dressing for deployment, deliver the dressing, and hold for 3 minutes. The mean estimated blood loss was 55 ⫾ 54 mL (range 10 to 143 mL). No sutures, clips, or additional hemostatic agents were used
512 Table 2
The American Journal of Surgery, Vol 197, No 4, April 2009 Blood laboratory information of chronic study Postoperative P Preoperative day 7 value*
Body weight WBC Neutrophil Lymphocyte Monocyte Eosinophil RBC HGB HCT MCV MCH MCHC
(kg) (x103/L) (%) (%) (%) (%) (x106/L) (g/dL) (%) (fL) (pg) (g/dL)
57 16.9 38 57 2 2 5.7 10 29.7 52.7 17.7 33.5
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
11 2.4 13 14 .6 1.7 1.2 1.2 3.2 4.9 1.5 .8
59 15.9 41 54 4 2 4.9 8.6 26.4 54.8 17.8 32.6
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
17 2.6 9 8 1 1.5 .5 .5 1.6 4 1.3 1
.6 .6 .8 .7 .1 .9 .4 .2 .2 .6 .9 .2
WBC ⫽ white blood cell count; RBC ⫽ red blood cell count; HGB ⫽ hemoglobin; HCT ⫽ hematocrit; MCV ⫽ mean cell volume; MCH ⫽ mean cell hemoglobin; MCHC ⫽ mean cell hemoglobin concentration. *Comparison between preoperative and postoperative with t test.
during the operation. The chitosan dressing was easily applied and held in place by using a laparoscopic fan-retractor. Venographic imaging showed no clot formation in the injured vessels. No significant postoperative decline in hematocrit and hemoglobin levels was seen in the chronic animals (Table 2). There was no clinical evidence of rebleeding,
such as hematoma or sanguineous ascites. The chitosan dressing was observed to be adherent to the IVC injury site at necropsy. Microscopic examination of the repaired IVC revealed that the chitosan was partially degenerated into small particles, which elicited the moderate chronic inflammation with granulation tissue. The particles were both extracellular and intracellular, the smaller ones (10 –100 m) within the cytoplasm of foreign body macrophages (Figure 1). There was no accumulated clot in the vessel lumen.
Comments The incidence of iatrogenic vena caval injury is very low but has been reported for a variety of laparoscopic surgical procedures.10 –13 Laparoscopic repair of vena caval injury sometimes can be troublesome due to limited exposure and poor visibility. It is highly recommended to convert to an open procedure if a vena caval injury has occurred. Nazhat et al reported 2 cases of IVC injury during pelvic and para-aortic node dissection in gynecological procedures.13 These injuries were repaired with an immediate laparotomy or a laparoscopic procedure. The laparotomy patient lost a significant amount of blood after removal of pneumoperitoneum pressure and required transfusion of 4 units of packed
Figure 1 (Top left) Gross image shows perforation injury site (marked by arrow) on the intimal surface of the IVC. (Top right) Low magnification image shows that the chitosan (C) dressing material has been incorporated into adventitia side of the IVC wall with moderate chronic inflammation (original magnification 25⫻, Movat pentachrome stain). (Bottom left) Higher magnification image shows that chitosan material (C) was broken down into small spherules, surrounded by inflammatory cells, primarily macrophages and lymphocytes. (Bottom right) Small chitosan spherules (⬃15–100 m, marked by arrow heads) engulfed by macrophages and multinucleated macrophages are visible (original magnification 400⫻, Movat pentachrome stain).
H. Xie et al.
Laparoscopic IVC injury repair using chitosan
red blood cells. An earlier national survey found that vascular injuries occurred in .25% of laparoscopic cholectectomy cases.1 Usal et al reported a total of 3 major vascular injuries among 2,589 laparoscopic cholectectomy procedures. These injuries involved the portal vein, aorta, and vena cava, and were repaired by exploratory laparotomy.14 Major vascular complications occur with an incidence of 1.98% in urological procedures.3 Thiel et al reported 4 cases of IVC injury during a right radical nephrectomy. These injuries were treated using laparoscopic vascular suturing techniques and were accompanied by a an average blood loss of 980 mL.4 The authors concluded that injury to the fragile vena cava can be managed laparoscopically by surgeons with extensive laparoscopic experience. In particular, surgeons must be meticulous during intracorporeal suturing.4 The external chitosan dressing is a hemostatic agent approved by the US Food and Drug Administration (FDA) for emergency treatment of severe hemorrhage to surface wounds. This chitosan dressing has demonstrated efficacy for a variety of traumatic injuries.5 The hemostatic action of chitosan is believed to be achieved through a combination of wound sealing and the promotion of local clot formation by erythrocyte agglutination and platelet activation.5,7 The dressings used in previous studies were a 100 ⫻ 100 ⫻ 2-mm thick square dressing with nonabsorbable polyethylene backing.5 The chitosan dressing in this study replaced the nonabsorbable backing with a bioabsorbable thin film. The current dressing is designed to provide enhanced compliance and bioabsorbability, as well as more uniform tissue adhesion and good resistance to dissolution in blood. In this study, the bioabsorbable chitosan dressing was immediately effective and provided reliable hemostasis to the vena caval injury. This chitosan dressing is easy to use laparoscopically because the chitosan immediately adheres to tissue. All of the IVC injuries were repaired with a single chitosan dressing application and no repairs exhibited any delayed bleeding. No postoperative infection or venous thrombosis was observed. Histological examination of the repaired IVC and surrounding tissue revealed no evidence of biological incompatibility. Compared to currently available topical hemostatic methods, the bioabsorbable chitosan dressing has several advantages. The chitosan dressing provides a convenient and rapid method to control bleeding by adhesively sealing the wound site. Use of the chitosan dressing can simplify the laparoscopic vascular repair procedure and save time when a vascular injury occurs. Clinically significant uses of the chitosan dressing in laparoscopic surgery are numerous. The chitosan dressing can be used to control bleeding from vena caval injury but also for bleeding from visceral organs after routine biopsy and resection, laparoscopic portal bleeding, or fluid leakage from injured organs. There are several limitations to this experimental study. Currently, the chitosan dressing is only approved by the FDA for external use and it must be removed after initial
513 application. However, emergency use of the dressing may provide time for the surgeon to plan a rescue strategy or to perform the operation. Another concern is that our porcine model had very little retroperitoneal fat compared to humans; therefore, exposure of an IVC injury in humans may be more difficult and the chitosan dressing may not be effective on fatty tissue. Finally, this study had no control group because no IVC injury can be treated with a topical hemostatic agent alone at the present time. Although the IVC injury was created with a significant fatal IVC bleeding, the fate of untreated animals (or animals treated with gauze sponge compression alone) is unknown in the current model. The chitosan dressing should also be evaluated in a long-term biocompatibility study before human use.
Conclusions Our study results indicate that vena caval injury can be repaired laparoscopically with a bioabsorbable chitosanbased hemostatic dressing. Application of the chitosan dressing is not technically demanding and immediately seals the wound. This technique has the potential for achieving laparoscopic control of hemorrhage from solid organs as a result of surgical injury or following trauma. Further long-term studies should be performed prior to human clinical trials.
Acknowledgment The authors would like to express their gratitude to Ky Dehlinger, D.V.M., and Teresa Malarkey of the Legacy Clinical Research and Technology Center for assistance in the animal surgeries and postoperative care.
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