Bleeding is common after liver resection and establishing hemostasis with sutures or argon beam coagulation (ABC) can be difficult. In our laboratory, concentrated albumin applied to the liver surface before ABC results in sealing of the resected surface of the liver, including closure of blood vessels not generally seen with standard ABC.
Hemorrhage is a major cause of death in both civilian and military trauma. The liver is the most commonly injured organ in abdominal trauma. Liver and other solid encapsulated organs, such as the spleen and kidney, present unique challenges to the surgeon because of the lack of internal structural elements, cause suture to hold poorly. Hemorrhage is life-threatening in liver injury, as the liver is a highly vascular organ, and injuries to it are frequently accompanied by hypothermia and iatrogenic hemodilution, compromising native coagulation.
The argon beam coagulator (ABC) quickly coagulates bleeding tissues. An ABC is a non-contact device that conducts radio-frequency current to tissue along a jet of inert, non-flammable argon gas. A grounding pad placed under the patient that allows current to flow from the tip of the probe to the tissue. Argon gas has a lower ionization potential than air and consequently directs the flow of current. The argon gas may also blow away blood and other liquids on the tissue surface, enhancing visualization of the bleeding site as well as eliminating electric current dissipation in the blood. Smoke is reduced because the argon gas displaces oxygen and inhibits burning.
The mechanical properties of various human albumin concentrations were characterized in in vitro studies. Concentrations ranging from 34% to 52% in 2% increments were examined by using the argon beam coagulator to bond albumin solder to porcine liver obtained freshly from a supermarket on the day of delivery from the slaughterhouse. The viscosity of albumin increases with concentration. At concentrations above 40%, the layer of albumin becomes increasingly difficult to bond to the underlying tissue. Typically, concentrations above 40% require manual spreading to create a sufficiently thin layer of albumin that bonding is readily achieved during coagulation. This finding is supported by others who have cited 45% as the cut-off concentration of albumin solder for ease of handling and efficacy. Therefore, 38% albumin was selected because it contains the highest protein density that remained workable.
A series of pre-clinical animal studies, has established that healing of topically-applied 38% albumin with argon beam coagulation (1) significantly reduces the number of rebleeds compared to argon beam coagulation alone and (2) is tolerated and healed by the body in a way that is substantially equivalent to argon beam coagulation alone. Both methods readily stop bleeding of the liver, both leave residual coagulated albumin remnants, and both encapsulate and digest these remnants over periods of time up to a year.
In a randomized pre-clinical study, heparinized pigs underwent non-anatomic lobe resection without hepatic vascular isolation. This study evaluated the effectiveness of using 38% albumin with an argon beam coagulator to stop bleeding during liver surgery. The study compared using an argon beam coagulator alone (ABC) with the argon beam coagulator with the application of 38% albumin (ABCA) to the resected liver surface. A non-anatomical resection of a lobe of the liver was made. Vessels larger than 5mm diameter were ligated. Proximal digital compression was employed to reduce blood oozing during the repair in both the control group and the treatment group. Rebleeding data from 28 liver lobes indicated that ABCA reduced the number of rebleeding episodes and the time of ABC application versus ABC alone. Although blood loss in the two groups was not statistically significantly different, a trend toward less blood loss in the ABCA group was apparent.
Based on the success of the acute study, we embarked upon a chronic pre-clinical study to compare healing responses between ABC and ABCA repairs at one and three months. Twenty domestic swine received non-anatomic partial hepatectomies similar to that described above for the acute studies. Follow-up at 30 and 90 days showed that all animals exhibited acceptable weight gain post-operatively and no catastrophic failures, such as liver failure, sepsis or exsanguination, occurred. No differences in liver function were observed between the two groups. No differences in post-surgical adhesion were found. Histology showed remnants of denatured albumin in both groups at day 30. The denatured albumin in the ABC only case came from coagulated blood. Denatured albumin was also seen at 90 days. Both groups had benign infammatory response at the site of injury at 90 days. The addition of albumin solder was not associated with any additional morbidity or significant added inflammation.
A long-term study was started to evaluate host response to albumin after 6 and 12 months. Coagulated albumin was still present in small amounts at 6 and 12 months after liver repair in both the ABC and ABCA groups. Inflammation was slightly higher in the ABCA group at 6 months, but was not significant. Inflammation was not different at 12 months. Peritoneal adhesions of the repaired site were similar in both ABC and ABCA groups.
2012R. McCargar, H. Xie, K. Price, S. A. Prahl, "In vitro mechanical assessments of laser-welded vascular anastomoses using water as the chromophore and dissolvable extruded albumin stents," Lasers in Surgery and Medicine, 44, 330-338 (2012).
Y. Wadia, S. A. Prahl, "Biocompatible denatured albumin lamina," United States Patent. No. RE 43,134, (2012).
2010G. R. Mueller, P. D. Hansen, R. F. Wolf, K. W. Gregory, S. A. Prahl, "Hemostasis after Liver Resection Improves after Single Application of Albumin and Argon Beam Coagulation.," J Gastrointest Surg, 14, 1764-1769 (2010).
2004Y. Wadia, S. A. Prahl, "Biocompatible albumin lamina and method," United States Patent. No. 6,680,063, (2004).
H. Xie, R. F. Wolf, A. P. Burke, S. B. Gustafson, K. W. Gregory, S. A. Prahl, "Concentrated Albumin as a Biological Glue for Hemorrhage Control on Hepatic Resection with Argon Beam Coagulation," J Biomed Mater Res, 71B, 84-9 (2004).
2003H. Xie, R. F. Wolf, J. S. Teach, A. Burke, K. W. Gregory, S. A. Prahl, "Concentrated Albumin for Hemorrhage Control on Hepatic Resection with Argon Ion Beam Coagulation: A Long-term Evaluation in a Porcine Model," 2003 Annual Meeting Transactions, (2003).
H. Xie, B. S. Shaffer, S. A. Prahl, K. W. Gregory, "Laser Ureteral Anastomosis Using Intraluminal Albumin Stent in a Porcine Model," Lasers Surg Med, 32, 294-8 (2003).
2002T. P. Moffitt, D. A. Baker, S. J. Kirkpatrick, S. A. Prahl, "Mechanical Properties of Repaired Liver Using an Argon Beam Coagulator with Albumin," SPIE Proceedings on Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems XII, 4609, 178-185 (2002).
T. P. Moffitt, D. Baker, S. J. Kirkpatrick, S. A. Prahl, "Mechanical Properties of Coagulated Albumin and Failure Mechanisms of Liver Repaired Using an Argon Beam Coagulator with Albumin," J. Biomedical Materials Research (Applied Biomaterials), 63, 722-728 (2002).
R. F. Wolf, H. Xie, J. Petty, J. S. Teach, S. A. Prahl, "Argon Ion Beam Hemostasis with Albumin Following Liver Resection," Am. J. Surg., 183, 584-587 (2002).
H. Xie, R. Wolf, J. Petty, A. Burke, J. S. Teach, K. W. Gregory, S. A. Prahl, "Hemostasis After Partial Hepatectomy Using Argon Beam Coagulation and a Concentrated Albumin," SPIE Proceedings of Lasers in Surgery: Advanced Characterization, Therapeutics and Systems XII, 4609, 186-194 (2002).
H. Xie, B. S. Shaffer, S. A. Prahl, K. W. Gregory, "Intraluminal Albumin Stent Assisted Laser Welding for Ureteral Anastomosis," Laser Surg. Med., 31, 225-229 (2002).
2000Y. Wadia, H. Xie, M. Kajitani, S. A. Prahl, "Liver Repair and Hemorrhage Control Using Laser Soldering of Liquid Albumin in a Porcine Model," SPIE Proceedings of Lasers in Surgery, 3907, 74-81 (2000).
Y. Wadia, H. Xie, M. Kajitani, S. A. Prahl, K. G. Gregory, "Liver Repair and Hemorrhage Control Using Laser Soldering of Liquid Albumin in a Porcine Model," ASAIO Journal, 46, 232 (2000 abstract only).
H. Xie, B. S. Schafer, S. A. Prahl, K. W. Gregory, "Laser Welding with an Albumin Stent: Experimental Ureteral End-to-End Anastomosis," SPIE Proceedings of Lasers in Surgery, 3907, 215-220 (2000).
1999S. A. Prahl, "Tissue Welding Using Solid Albumin Solder and a Millisecond Pulsed Laser," Proceedings of the Oregon Academy of Science, 35, 58 (1999 abstract only).
H. Xie, B. S. Schafer, S. A. Prahl, K. W. Gregory, "Sutureless End-to-End Ureteral Anastomosis Using a New Albumin Stent and Diode Laser," 1999 International Conference on Biomedical Optics, 3683, 398-406 (1999).