Fibrin gel limits intra-abdominal adhesion formation.

Autologous fibrin gel (FG) has recently been reported efficacious in hepatic injury; the effects of fibrin compounds on intra-abdominal adhesion formation is controversial. This study evaluated intra-abdominal adhesion formation in a rabbit devascularization model. Seventeen New Zealand rabbits were anesthetized and laparotomy was done. The uterine horns were abraded to punctate bleeding followed by bilateral uterine devascularization. Treatment consisted of 10 cc saline control (c) or FG applied to the uterine horns. Peritoneal lavage was done at 15 minutes for red blood cell (RBC) analysis. Autopsy was performed at 1 week. Adhesions were graded from grade 0 (no adhesions) to grade III (dense adhesions). Adhesion grading revealed no difference in average adhesion grade between FG and C with small bowel (1.0 +/- 1.3 vs 0.5 +/- 1.0); bladder (2.1 +/- 1.1 vs 2.4 +/- 1.2); or uterus (1.2 +/- vs 2.0 +/- 1.2). Adhesion grade was significantly less in FG compared to C for the colon and the abdominal incision (0.4 +/- 0.5 vs 1.7 +/- 1.1 and 1.2 +/- 1.1 vs 3.0 +/- 1.2; P less than 0.05 by t-test). There were no differences in lavage RBC count between FG and C (13.1 x 106 +/- 4.1 x 10(6) vs 8.7 x 106 +/- 3.2 x 10(6)). Fibrin gel significantly decreased incisional and colonic adhesions and reduced other abdominal adhesion formation by a nonhemostatic dependent mechanism.     

Use of Sodium Hetastarch (Hespan) Solution for Reduction of Postoperative Adhesion Formation in Rabbits

A study was conducted to determine the effect of sodium hydroxy ethyl starch (Hespan) on primary adhesion formation in a rabbit model. Hespan is a readily available volume expander. This was a randomized, double-blinded animal model in which New Zealand white rabbits were subjected to midline celiotomy. Adhesions were created by abrasion in both uterine horns, adjacent bowel, and peritoneum. Necropsies were performed at the 2-week interval and adhesions were graded. Significant decreases in type II and type III adhesions (p =. 032 and p =. 020, respectively) were demonstrated in Hespan-treated animals. Sodium hetastarch appears to decrease signifcant adhesion formation in treated animais and may have a roie as an adjunct for postsurgical prevention.     

Ibuprofen inhibition of postsurgical adhesion formation: A time and dose response biochemical evaluation in rabbits

Recently, a reduction in postoperative adhesion formation in rabbits which received high-dose ibuprofen (280 mg/kg/day) treatment in the perioperative interval was reported. Because these results could have resulted from a nonspecific effect of ibuprofen, the effects of ibuprofen on peritoneal injury in a time and dose response fashion was evaluated. Seventy rabbits were assigned to seven groups. All rabbits received a dose of ibuprofen 1 hr prior to surgery. The time of the second dose was either 8 or 12 hr after the surgical procedure; 8 hr for groups A, C, and E; 12 hr for groups B, D, and F (A, B: 70 mg/ kg; C, D: 35 mg/kg; E, F: 17.5 mg/kg, respectively). Thereafter, rabbits received further dosing every 6 hr to complete a total 10-dose regimen. Group G served as a nontreatment control. Surgical injury was induced by either abrasion or ischemia of the right uterine horn. Immediately after closing the incision, 10 μCi of ¹⁴C-labeled glucosamine and 10 μCi of ¹⁴C-labeled proline were injected into each rabbit. All rabbits underwent a second laparotomy on the fifth postoperative day for evaluation of adhesion formation. Uterine tissue adjacent to the site of uterine healing was excised for determination of glycosaminoglycan and collagen concentration. In the nontreatment control group G, 5 of the 10 rabbits had severe grade 2 adhesions at the time of second laparotomy, 3 had grade 1 filmy adhesions, and 2 had no adhesions. This is in marked contrast (P < 0.025) to the group that received ibuprofen at 70 mg/kg/day with the first postoperative dose 8 hr after surgery (group A). In this group, no rabbits had severe grade 2 adhesions, 3 rabbits had filmy grade 1 adhesions, and 7 rabbits were free of pelvic adhesions. A gradual tendency towards more adhesions and more severe adhesions was apparent in groups B-F as the dose of ibuprofen was decreased and the time of first postoperative injection was prolonged. The recovery of ¹⁴C-labeled glucosamine from the glycosaminoglycan extraction demonstrated a positive correlation between the cpm recovered and the severity of adhesions formed. Groups A and B had, overall, the lowest ratios of glucosamine (1.47 ± 0.08 and 1.56 ± 0.09, respectively) which were statistically different from the nontreatment control group G (1.76 ± 0.11, P < 0.05). There was also a positive correlation between the formation of severe adhesions and the ratio of ¹⁴C-labeled proline recovered by collagen extraction. Those rabbits which did not develop adhesions had an average collagen ratio of 1.48 ± 0.03; those with grade 1, filmy adhesions, 1.68 ± 0.04; those with grade 2 adhesions, 1.89 ± 0.04 (P < 0.05 for all treatment vs control groups). Rabbits undergoing either abrasion or devascularization procedures of their uterine horn manifested a significant reduction in peritoneal adhesion formation with perioperative ibuprofen treatment. Further, a positive correlation existed between the formation of glycosaminoglycans and collagen in the site of uterine healing and the subsequent formation of adhesions.     

Vitamin A deficiency impairs colonic healing but not adhesion formation in germ-free and conventional rats.

Vitamin A is well recognized as a factor of major importance in epithelial and connective tissue repair mechanisms. Recently it was shown that vitamin A deficiency caused overgrowth and translocation of intestinal bacteria in rats. The aim of this study was to investigate the healing of colonic anastomoses and formation of postsurgical adhesions in vitamin A-deficient germ-free and conventional rats. Fourteen germ-free and 10 conventional rats were allocated to four groups: germ-free rats not given vitamin A, germ-free rats given vitamin A, conventional rats not given vitamin A, and conventional rats given vitamin A. All rats underwent surgery for colonic anastomosis. Seven days afterward, they were euthanized, and the bursting pressure of colonic anastomosis and formation of peritoneal adhesions were evaluated. The bursting pressures in groups not given vitamin A were lower than in groups given vitamin A. The adhesion scores in germ-free groups were lower than in conventional groups. These findings demonstrated that vitamin A had an important role in healing of colonic anastomoses whether in the presence or absence of intestinal flora, and that intestinal bacteria had a greater effect than vitamin A on formation of postsurgical adhesions. This may suggest that the mechanism of healing of colonic anastomoses differs from that of postsurgical adhesion formation.     

Surgical glove powder and intraperitoneal adhesion formation. An appeal for the use of powder-free surgical gloves.

Intraperitoneal adhesion formation is a major cause of infertility and/or intestinal obstruction. Among the many well-known aetiological factors responsible for peritoneal inflammatory reaction is surgical glove powder; for example, cornstarch powder. A study was undertaken on 30 rats to determine whether cornstarch powder caused intraperitoneal adhesions. The rats were randomised into two groups under laboratory conditions. Laparotomies were performed on all the rats and trauma inflicted to the right uterine horn. The study group received cornstarch powder suspended in normal physiological salt solution intraperitoneally, and the control group received only normal physiological salt solution. Peritoneal adhesions were evaluated after 2 weeks and statistically analysed with a t-test and 95% confidence intervals. The study group showed a statistically significantly higher incidence of intraperitoneal adhesions (P = 0.0003). It is concluded that cornstarch, as used on surgical gloves, caused peritoneal adhesions and should therefore be removed before surgery. Powder-free gloves are more suitable for preventing adhesion formation.     

PVA gel as a potential adhesion barrier: a safety study in a large animal model of intestinal surgery

Background

Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model.

Methods

Experiments were performed in a pig model with median laparotomy and intestinal anastomosis following small bowel resection. The primary endpoint was the safety of PVA on small intestinal anastomoses. We also measured the incidence of postoperative adhesions in PVA vs. control groups: group A (eight pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared to group B (eight pigs), which had no anti-adhesive barrier. Animals were sacrificed 14 days after surgery and analyzed.

Results

All anastomoses had a patent lumen without any stenosis. No anastomoses leaked at an intraluminal pressure of 40 cmH₂O. Thus, anastomoses healed very well in both groups, regardless of whether PVA was administered. PVA-treated animals, however, had significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn PVA group also had weaker adhesions and trended towards fewer adhesions to adjacent organs.

Conclusion

These results suggest that PVA gel does not jeopardize the integrity of intestinal anastomoses. However, larger trials are needed to investigate the potential of PVA gel to prevent adhesions in gastrointestinal surgery.     

Problems of fibrin adhesion of the nerves

Although the fibrin adhesion enjoys increasing success in many areas of surgery, it has not, however, become fully established in nerve anastomosis. It was in this area particularly that significant advantages were expected. As the fibrin clot dissolved prematurely, however, and dehiscences ensued, antifibrinolytic substances had to be added to the adhesive. Fibroses occurred frequently as a result, which to date encumber nerve adhesive. We examined various factors of the adhesive system for their fibrosis-inducing effect. We were able to establish that no additional fibrosis-promoting effect emanated from aprotinin and the fibrin clot as a supply barrier, whereas thrombin, Factor XIII and fibronectin possess a fibrosis-promoting effect.     

Fibrin sealant in high-risk colonic anastomoses

The use of fibrin sealant has been advocated to enhance the healing of high-risk intestinal anastomoses. Colonic anastomoses were performed in 162 rats randomly assigned to four groups: control animals with or without fibrin sealant applied to the anastomosis and steroid-treated animals with or without fibrin sealant. At five days postoperatively, the use of steroids alone significantly reduced the anastomotic bursting pressure (ABP) and enhanced abscess and adhesion formation. The addition of fibrin sealant to the anastomosis in steroid-treated animals did not improve ABP and, in fact, further increased abscess formation. In control animals, the use of fibrin sealant also reduced ABP and enhanced abscess and adhesion formation. By ten days, there was no difference in ABP among the groups, and the rate of abscess formation was reduced in all groups. These findings indicated that short-term treatment with steroids delayed colonic anastomotic healing. Fibrin sealant did not enhance the integrity of these high-risk anastomoses. The present data do not support the use of fibrin sealant in high-risk colonic anastomoses.     

Fibrin glue inhibits intra-abdominal adhesion formation

To determine the effect of fibrin glue on intra-abdominal adhesion formation, 45 rats were randomized to three groups. Each animal received two adhesion models. Group 1 received no further treatment. Groups 2 and 3 had the adhesion models covered with fibrinogen from fresh frozen plasma (1.77 g/L) and cryoprecipitate (23.6 g/L), respectively. In group 1, 13 of 15 rats had high-grade adhesions in both models. In group 2, high-grade adhesions were noted in nine of 15 rats in model 1 and in 12 of 15 rats in model 2. In group 3, however, high-grade adhesions were seen in only three of 15 rats in model 1, with 11 rats having no adhesions, and in only two of 15 rats in model 2. Histologic analysis suggested accelerated healing in group 3. We conclude that (1) fibrin glue inhibits intra-abdominal adhesion formation in rats, (2) the inhibitory action is dependent on the fibrinogen concentration of the fibrin glue, and (3) adhesions are reduced by fibrin glue regardless of whether the peritoneal defect is closed.     

Case Report: Intestinal Obstruction as a Late Presentation of Perforation of the Transverse Colon Following Blunt Abdominal Trauma

Colonic perforation associated with blunt abdominal trauma is rare. Even more so is the formation of an inflammatory adhesion preventing leakage into the peritoneum. We present a case of the above in which the patient presented 1 month later with intestinal obstruction which required surgical intervention. A 38-year-old male, victim of a road traffic accident (RTA), presented with multiple fractures in his extremities which had to be operated on and was later discharged without complications. He was readmitted 1 month following the trauma with intestinal obstruction. During the operation, a stenosing colonic adhesion due to bowel perforation following blunt abdominal trauma was discovered. Resection of the transverse colon and a termino-terminal colo-colonic anastomosis was performed.     

Die Beeinflussung des Regenerationserfolges einer geklebten Nervenanastomose durch lokale Corticoidapplikation

Although the fibrin adhesion is being used in many areas of surgery with increasing success, it has, however, not become fully established in nerve anastomosis. At the beginning fibrin clots dissolved prematurely and dehiscences ensued. Antifibrinolytic substances had to be added to the adhesive to stabilize the clot. As a result fibroses occurred frequently, which up to now encumber nerve adhesive. The conventional suture technique is still not convincing also. Because reports showed a beneficial influence on conventional nerve sutures, the object of this study was a comparison between conventional suture technique and nerve anastomosis by fibrin adhesives with and without additive of corticosteroids. Electrophysiological methods were used, because regeneration is clinically determinating. The results do not recommend the use of lokal corticosteroids in nerve anastomoses fixed by fibrin adhesive.     

Innovation and Change in Medical Technology: Interactions Between Physicians and Engineers

Intraperitoneal adhesions following surgical procedures cause considerable morbidity. Hyaluronic acid/carboxymethylcellulose (HA/CMC) films have been shown to be effective agents in decreasing adhesion formation. However, when there is an inadvertent leak of bowel contents into the peritoneum due to incomplete anastomosis, adhesion formation about a defect in order to prevent further leakage and to promote healing of the wound is important for the prevention of morbidity and mortality. The purpose of this study was to determine if an antiadhesion film (HA/CMC) impairs these potentially beneficial adhesions to bowel anastomoses, thus predisposing them to enteric leaks with subsequent peritonitis. Sixty-four rabbits were divided in two groups, each undergoing a complete or partial (90% anastomosis to simulate anastomotic leak) large bowel anastomosis. Half of each of the above groups were treated by wrapping a HNCMC film over the anastomosis and the other half were untreated controls. These two subgroups were then further divided equally and sacrificed at either 7 or 14 days for evaluation of anastomosis integrity and strength. The average anastomtic bursting pressures did not change significantly between those groups treated with HMCMC when compared to untreated controls at 7 or 14 days or in the complete or partial anastomosis group (Student's t test). Adhesion formation to the anastomosis was not impaired in either group independent of HAKMC film application. This study suggests that while HA/CMC film has been shown to decrease adhesions in other models, healing of u rabbit colonic unastomosis even in the presence of an anastomotic defect takes place, further suggesting that the stimulus for adhesion formation can overcome the antiadhesion properties of HA/CMC. Therefore, HA/CMC is a potentially safe adjuvant for preventing postoperative intraabdominal adhesions.     

Adhesions and adhesiolysis: the role of laparoscopy.

BACKGROUND: Adhesions commonly result from abdominal and pelvic surgical procedures and may result in intestinal obstruction, infertility, chronic pain, or complicate subsequent operations. Laparoscopy produces less peritoneal trauma than does conventional laparotomy and may result in decreased adhesion formation. We present a review of the available data on laparoscopy and adhesion formation, as well as laparoscopic adhesiolysis. We also review current adjuvant techniques that may be used by practicing laparoscopists to prevent adhesion formation. DATABASE: A Medline search using "adhesions," "adhesiolysis," and "laparoscopy" as key words was performed for English-language articles. Further references were obtained through cross-referencing the bibliography cited in each work. DISCUSSION: The majority of studies indicate that laparoscopy may reduce postoperative adhesion formation relative to laparotomy. However, laparoscopy by itself does not appear to eliminate adhesions completely. A variety of adjuvant materials are available to surgeons, and the most recent investigation has demonstrated significant potential for intraperitoneal barriers. Newer technologies continue to evolve and should result in clinically relevant reductions in adhesion formation.     

Prevention of adhesion to prosthetic mesh in incisional ventral hernias: comparison of different barriers in an experimental model

BACKGROUND: The purpose of this study was to compare the intra-abdominal adhesion formation following ventral hernia repair by using oxidized regenerated cellulose (ORC) as a barrier underneath polypropylene mesh (PPM), and sodium hyaluronate/carboxymethylcellulose (HA/CMC)-coated PPM. METHODS: A ventral abdominal defect was created in each of 30 male rats which were divided into three groups. In group 1 (control) the defect was repaired with PPM; in group 2 ORC was laid over the viscera and the defect was repaired with PPM, and in group 3 HA/CMC-coated PPM was used for the repairing procedure. On the 28th postoperative day all the rats were sacrificed and adhesions were evaluated by laparoscopic exploration followed by histopathological examination. RESULTS: Animals treated with ORC and PPM, and HA/CMC-coated PPM showed significantly less adhesions than the control group (p = 0.026) and the intra-abdominal adhesions of the rats in these two groups were significantly easier to release than in the control group (p = 0.001). There was no significant difference between the ORC and HA/CMC groups. CONCLUSIONS: ORC used together with PPM is as effective as HA/CMC-coated PPM and ORC can be used as an adhesion barrier in intra-abdominal hernia repair.     

Effects of hyaluronic acid/Carboxymethylcellulose gel on bowel anastomoses in the New Zealand white rabbit

Intra-abdominal adhesions form in more than 90% of patients undergoing major abdominal surgery and can lead to significant complications. Application of a bioresorbable gel consisting of chemically modified hyaluronic acid (HA) and carboxymethylcellulose (CMC) has shown promise as a means of preventing intra-abdominal adhesions, but there have been concerns that the presence of the gel might interfere with the integrity and healing of bowel anastomoses. We tested the effects of HA/CMC gel on adhesion formation and anastomotic healing in 60 New Zealand white rabbits after transection and complete (100%) or incomplete (90%) anastomosis of the ileum. Half of the animals underwent application of HA/CMC gel and half served as control subjects. Animals were killed at 4, 7, or 14 days after surgery. Anastomotic adhesions were scored in a blinded fashion. Integrity of the anastomosis was tested by measuring bursting pressure at the anastomotic site and in an adjacent section of intact bowel. With complete anastomosis, HA/CMC gel significantly reduced adhesion formation at 7 and 14 days after surgery (P<0.05), but gel application did not inhibit adhesion formation when the anastomosis was incomplete. Anastomosed segments of bowel burst at a lower pressure than intact bowel 4 days after surgery, but bursting pressures were normal at 7 and 14 days. Burst pressures of anastomoses receiving an application of HA/CMC gel were nearly identical to control anastomoses at all three time points. HA/CMC gel did not interfere with the normal healing process of bowel anastomoses. Furthermore, HA/CMC gel decreased adhesion formation after complete anastomoses, yet it did not affect adhesion formation in the presence of anastomotic disruption.     

Studies on prevention of intra-abdominal adhesion formation by fibrin sealant. An experimental study in rats

The preventive effect of fibrin sealant on post-operative formation of peritoneal adhesions was investigated in rats. Intraperitoneal adhesion formation was induced with a standardized, sutured defect in the peritoneum. The influence of sealant thickness and lifetime was evaluated by application of a thin and a thick layer of fibrin sealant containing high or low concentration of antiplasmin. Assessment of adhesion formation one week post-operatively showed significantly less adhesion to the defects covered with the thick layer of sealant having high or low antiplasmin concentration as compared with defects having only a thin sealant layer or control rats without sealant.     

Trauma induces a hypercoagulable state that is resistant to hypothermia as measured by thrombelastogram

Background

The aim of this study was to test the hypothesis that severely injured trauma patients would be hypercoagulable compared with controls measured by thromboelastography and that this hypercoagulability would persist over a broad range of temperatures.

Methods

A prospective study evaluating the effects of temperature on coagulation in trauma patients with Injury Severity Scores ≥ 15 and controls was completed. Thromboelastography was performed 24 hours after admission at 4 temperatures ranging from 32°C to 38°C.

Results

Ninety-two subjects (46 patients) were analyzed. Patients had a median Injury Severity Score of 20 (interquartile range, 16–26). Time to clot formation increased (P < .001) and fibrin cross-linking decreased (P < .01) in both groups as temperature decreased. Between groups, time to clot formation, fibrin cross-linking, and clot strength were significantly different at each temperature (P < .01), with patients being more hypercoagulable. Time to clot formation and fibrin cross-linking were more affected by temperature in controls compared with patients (P < .02).

Conclusions

Severely injured patients are more hypercoagulable than controls throughout a broad range of temperature. Decreasing temperature has a greater effect on coagulation in controls compared with patients.     

Intravascular fibrinolysis of small-vessel thrombosis

The effect of intraarterial fibrinolysin infusion on the prevention and treatment of vascular thrombosis in arterial and venous systems of large and small dogs was studied by use of a free groin flap model. Vessel patency and clot lysis after microvascular repair of the superficial caudal epigastric artery and vein were compared in 14 dogs that received prophylactic infusion of fibrinolysin and in 10 control dogs that did not. In 22 additional dogs, after the formation of a standard fibrin clot, arterial infusion of fibrinolysin was performed to determine its therapeutic effect on fibrin clot lysis. The results demonstrate that, after blunt trauma to peripheral vessels in the dog, prophylactic infusion of fibrinolysin has no significant effect on either vessel patency or percentage of local thrombus formation at the anastomatic site. From a therapeutic standpoint, fibrinolysin was effective in fibrin clot lysis in the large vessels (internal diameter 1.8 to 3.0 mm) of 7 of 10 dogs infused within 48 hours after thrombus formation, but was not effective in the small vessels (internal diameter 0.8 to 1.5 mm) of 11 of 12 small dogs with infusion as early as 1 hour after thrombus formation. The therapeutic effectiveness of the fibrinolytic agents to lyse preformed thromboses in small vessels appears doubtful.     

Comparative Evaluation of Adhesions to Intraperitoneally Placed Fixation Materials: A Laparoscopic Study in Rats

After laparoscopic ventral hernia repair, the nature of the adhesions to fixation materials or to mesh had not been clarified. We examined adhesion formation specific to the fixation material in rats. We designed an experimental laparoscopy setup, and placed four intraperitoneal fixation materials on the peritoneum of rats without a mesh graft. Another group of researchers documented the incidence and intensity of postoperative adhesion formation. The adhesion scores for the nickel-titanium anchor were significantly greater than those for polylactic acid (p = 0.004), a titanium tacker (p < 0.0001), and fibrin glue (p < 0.0001). No adhesions occurred in the fibrin glue group. Fibrin glue is the preferred fixation material because it produced no postoperative adhesions. The nickel-titanium anchor produced heavy adhesions but may be applicable for recurrent hernia cases and in patients with thin abdominal walls.