Comparative study of the efficacy of the common topical hemostatic agents with fibrin sealant in a rabbit aortic anastomosis model

OBJECTIVE: The purpose of this study was to compare the hemostatic efficacy of the common surgical hemostatic agents with fibrin sealant (FS) and to assess their functional strength to secure hemostasis in lieu of placing additional sutures. METHODS: End-to-end anastomosis of transected abdominal aorta was performed in moderately anticoagulated rabbits using 4 or 6 interrupted sutures. The suture line was covered either with gauze alone ("untreated") or with gauze plus Gelfoam, Avitene, Surgicel, FloSeal, or FS, following which blood flow was restored. Blood loss was absorbed by gauze and measured. The surviving rabbits were recovered and the repaired vessel was examined histologically 4 weeks after operation. The investigators were blinded to the treatment groups. Aortic anastomoses using 8 or 12 sutures (untreated) were also performed. RESULTS: Untreated 4-suture anastomosis of aorta resulted in a profuse hemorrhage with an average 108.0 +/- 19.2 (mean +/- SD) ml blood loss and 100% mortality (n = 4). FS application sealed the anastomoses, prevented blood loss (P < 0.01 vs untreated) and exsanguination of the rabbits (n = 4). Other hemostatic agents reduced the bleeding to varying degrees compared to the untreated animals (Gelfoam 66.4 +/- 17.6, Avitene 80.6 +/- 34, Surgicel 66.7 +/- 16.7, FloSeal 44.2 +/- 8.5 ml blood loss, n = 4/group), but the changes were not statistically significant. One to three rabbits in each group survived the operation. Six-suture aortic anastomoses, untreated, resulted in 67.7 +/- 21.8 ml blood loss and 100% survival (n = 6). Application of FS produced immediate and sustained hemostasis in all the animals (P < 0.01 vs untreated). Other hemostatic agents also reduced the bleeding (Gelfoam 42.5 +/- 10, Avitene 50.9 +/- 12.4, Surgicel 32.1 +/- 14, FloSeal 33.9 +/- 5.4 ml blood loss, n = 6/group), but the changes were not statistically significant. The 8- and 12-suture aorta repairs resulted in a moderate blood loss (43.9 +/- 19 and 21.3 +/- 14.9 ml, respectively), followed by a stable hemostasis that precluded the need to use any hemostatic agent. The aortic cross-clamping time of the 12-suture and time to hemostasis for both the 8- and the 12-suture techniques were significantly longer than those of the 4-suture plus FS application (P < 0.01, P < 0.01 and P < 0.05, respectively). CONCLUSION: In a moderate coagulopathy, FS was proven to be the most efficacious hemostatic agent, producing immediate and sustained hemostasis at the arterial anastomotic site. This high efficacy is in part attributed to the strong tissue adhesive property of this agent. FS application may potentially ease the anastomosis and shorten the duration of timely critical vascular procedures.     

A model for sidewall adhesions in the rabbit: reduction by an absorbable barrier

Despite use of surgical adjuvants, pelvic adhesions frequently develop following infertility surgery. Recently a resorbable biocompatible material, TC 7, has been designed to be used as a barrier to reduce adhesion formation. Reproducibly severe sidewall adhesions were only able to be created in one of six models tested. The model consisted of the following steps: excision of a full thickness 2 x 2-cm musculoperitoneal tissue mass, scraping of an adjacent 2-cm length of uterine horn, tamponading of all bleeding, and suturing (6-0 Vicryl) of normal tube and sidewall so as to directly approximate the traumatized tissues. Studies were conducted in 13 rabbits after creation of the bilateral sidewall and horn lesions, each serving as its own control. Choice of control and TC 7 sides was determined randomly. Adhesion formation was examined 2 weeks postoperatively. No residual material was noted at that time. Adhesion scores were the composite total of extent (0-4), type (0-4), and tenacity (0-3) of sidewall adhesions, and were significantly reduced on the TC 7 side as compared with the control side (mean 6.8 +/- 0.4 vs 9.0 +/- 0.3, median 6 vs 9, sign test P = 0.0032). No complications of use of the barrier were noted. It is concluded that use of TC 7, a resorbable biocompatible barrier, was able to significantly reduce postoperative adhesion formation on the rabbit sidewall.     

Evaluation of oxidized regenerated cellulose for prevention of postoperative intraperitoneal adhesions

Oxidized regenerated cellulose (ORC) is widely used to cover the denuded mesothelium and to promote hemostasis. We evaluated ORG in a rabbit model to assess the potential for adhesion reduction after uterine trauma and intestinal anastomosis. After surgery, a second laparotomy was done on postoperative day 7 for macroscopic evaluation of adhesion formation. The traumatized uterine horns wrapped in ORC had more numerous and higher grade adhesions compared with the non-surgical left, intact horns. However, when compared to the contralateral uterine horn which underwent trauma without ORG, a significant decrease in the grade of adhesion formation was noted. Rabbits undergoing intestinal anastomosis had the most pronounced degree of adhesion formation. Typically, the area of healing was encapsulated in a fibrin clot with adhesions attached to adjacent viscera. When ORC remained between the lesion and adjacent organs during mesothelial regeneration, adhesion formation decreased. However, the soft, gelatinous mass of ORC was also an effective nidus for clot formation. Where post-and intra-operative ooze produced a fibrin clot in the ORC, dense adhesions formed.     

Prevention of postsurgery-induced abdominal adhesions by electrospun bioabsorbable nanofibrous poly(lactide-co-glycolide)-based membranes

OBJECTIVES: The objective of this study was to evaluate the efficacy of nonwoven bioabsorbable nanofibrous membranes of poly(lactideco-glycolide) for prevention of postsurgery-induced abdominal adhesions. SUMMARY BACKGROUND DATA: Recent reports indicated that current materials used for adhesion prevention have only limited success. Studies on other bioabsorbable materials using a new fabrication technique demonstrated the promising potential of generating an improved and inexpensive product that is suitable for a variety of surgical applications. METHODS: All rats underwent a midline celiotomy. The cecum was identified and scored using an abrasive pad until serosal bleeding was noted on the anterior surface. A 1 x 1 cm of abdominal wall muscle was excised directly over the cecal wound. The celiotomy was then closed in 2 layers immediately (control) after a barrier was laid in between the cecum and the abdominal wall. All rats underwent a second celiotomy after 28 days to evaluate the extent of abdominal adhesions qualitatively and quantitatively. RESULTS: Cecal adhesions were reduced from 78% in the control group to 50% in the group using biodegradable poly(lactide-co-glycolide) (PLGA) nonwoven nanofibrous membranes (n = 10, P = 0.2) and to 22% in the group using membranes containing PLGA and poly(ethylene glycol)/poly(D,L-lactide) (PEG-PLA) blends (n = 9, P = 0.03). Electrospinning method also enabled us to load an antibiotic drug Cefoxitin sodium (Mefoxin; Merck Inc., West Point, PA) with high efficacy. The electrospun PLGA/PEG-PLA membranes impregnated with 5 wt% cefoxitin sodium, which amounts to approximately 10% of the systemic daily dose typically taken after surgery in humans, completely prevented cecal adhesions (0%) in rats. CONCLUSIONS: Electrospun nonwoven bioabsorbable nanofibrous membranes of poly(lactide-co-glycolide) were effective to reduce adhesions at the site of injury using an objective rat model. The membrane acted as a physical barrier but with drug-delivery capability. The combined advantages of composition adjustment, drug-loading capability, and easy placement handling (relatively hydrophobic) make these membranes potentially successful candidates for further clinical evaluations.     

Reduction of Adhesion Formation by Intraperitoneal Administration of Anti-inflammatory Peptide 2

Adhesion formation is a major source of postoperative morbidity and mortality. Therefore, the reduction of postoperative adhesion formation would be of clinical benefit. Various modalities have been shown to reduce adhesion formation, including fibrinolytic enzymes, nonsteroidal anti-inflammatory drugs, and barriers that reduce the apposition of sites of potential adhesion formation. This study examined the ability of a phospholipase A₂ inhibitor, anti-inflammatory peptide 2 (antinflammin), to reduce the formation of intraperitoneal adhesions in two rabbit models of adhesion formation. In the sidewall model, antinflammin was administered via Alzet miniosmotic pump for the entire postoperative interval, and there was a dose-dependent reduction in the area of the sidewall injury that was involved in adhesions to the cecum and the bowel. In the double uterine horn model, antinflammin was administered via Abet miniosmotic pump to the area of injury for either 1, 2, 3, or 7 days. Administration of antinflammin for as little as 24 h after surgery significantly reduced the extent of adhesion formation. Administration of the peptide for longer periods of time did not further increase the reduction in adhesion formation. These studies clearly demonstrate that postoperative administration of antinflammin to the site of injury reduced the formation of postoperative adhesions in two animal models.     

New adhesion formation after laparoscopic and conventional adhesiolysis

This study aimed to compare new adhesion formation after laparoscopic and conventional adhesiolysis. In a first operation, 24 rabbits underwent fixation of deserosated cecum (6 cm2) to the lateral abdominal wall to induce standardized adhesions. After 4 weeks, adhesiolysis was performed by laparoscopy (n = 12) or laparotomy (n = 12). Outcome was assessed by the incidence, extent, and location of adhesion reformation. After conventional adhesiolysis, new adhesions developed in all the rabbits, as compared with 75% after laparoscopic adhesiolysis. The extent of newly formed adhesions was significantly reduced (p <0.001) after laparoscopic adhesiolysis (368 ± 115 mm2) as compared with conventional adhesiolysis (2434 ± 245 mm2). There were no adhesions to trocar wounds, but adhesions to the abdominal incision were found in 33% of the conventional group. In a rabbit model comparing laparoscopic and conventional adhesiolysis in a standardized experimental setting, laparoscopic adhesiolysis is associated with a significantly reduced formation of new postoperative adhesions.     

Does hemodilution enhance coagulability?

Recent publications reported enhanced coagulability in hemodilution determined by TEG. In contrast, earlier reports have shown prolongation of in-vivo bleeding time in anemia. In order to take a closer look at this discrepancy undiluted and diluted anticoagulated blood samples (20 % with saline solution, hydroxyl-ethyl starch 6 % (HES), autologous platelet poor plasma (PPP)) were investigated by TEG (n = 10), ball (n = 10), and hook coagulometer (n = 15) as well as tests simulating primary hemostasis ex vivo (Platelet Function Analyzer PFA-100, n = 10). RESULTS: Dilution with plasma changed TEG parameters in a way, when started by recalcification of the blood sample, which is characteristic of enhanced coagulability (r decreased in all and k in 8 of 10 samples, maximal amplitude increased in 9 out of 10). With HES, changes in TEG parameters mainly indicated reduced coagulability (k increased in 7 out of 10, MA decreased in 10 out of 10). When the coagulation was additionally activated by PTT reagent (InTEG) the TEG parameters also mainly showed hypocoagulation with the three dilution solutions. Coagulation times with ball and hook coagulometers were significantly prolonged by dilution especially with saline (+ 25 % and + 17 %, p < 0.001). Dilution always significantly (often abnormally) prolonged closure time in PFA-100 (saline + 41 +/- 18 %, PPP + 37 +/- 20 %, HES + 69 +/- 24 %) demonstrating disturbance of primary hemostasis, particularly with HES. Conclusions: From the results obtained it can be concluded that the changes in the classical TEG (without addition of PTT-reagent), suggesting an enhanced coagulability, may be caused methodically as they are also found with autologous PPP. On the other hand, a disturbance of the primary hemostasis in hemodilution has to be taken into account from the results seen with the PFA-100 and a number of published data.     

Long-term results with triple valve surgery

BACKGROUND: Whether to use biological or mechanical prostheses and whether to repair or replace the tricuspid valve during primary and reoperative triple valve surgery remains controversial. The objective of the present study was to review our experience with primary and reoperative triple valve surgery using CarboMedics (CM) and Carpentier-Edwards (C-E) heart valves. METHODS: All 73 patients undergoing triple valve surgery since 1982 were prospectively followed at the Montreal Heart Institute valve clinic. Aortic valve replacement was performed with CM prostheses (57 patients) and with C-E prostheses (16 patients). Mitral valve replacement was performed with mechanical prostheses (56 patients) and with biological valves (14 patients). Mitral valve repair was done in 3 patients. Tricuspid valve annuloplasty or commissurotomy or both were performed in 66 patients and the tricuspid valve was replaced in 7 patients. Patient survival, complications, and the type of valve procedures were analyzed. RESULTS: Thirty patients averaging 62+/-10 years of age underwent primary triple valve surgery and 43 patients averaging 60+/-10 years of age underwent reoperative triple valve surgery (p = 0.5). Tricuspid repair consisted of annuloplasty with the Bex linear reducer (n = 47), the C-E ring (n = 13), or the De Vega technique (n = 5). Tricuspid valve replacement was done using the C-E pericardial prostheses. The 30-day mortality was 17% and 12% in patients with primary and reoperative surgery, respectively (p = 0.5) and patient survival averaged 80%+/-7%, 75%+/-8%, and 41%+/-15%, and 70%+/-7%, 57%+/-9%, and 50%+/-10%, respectively 1, 5, and 10 years following surgery (p = 0.5). The freedom rate from thromboembolism and from bleeding complications were 87%+/-6% and 95%+/-3% in primary and reoperative patients, respectively, 5 years following surgery. CONCLUSIONS: Triple valve surgery, either as a primary or a reoperative procedure, results in acceptable long-term survival with both mechanical and biological prostheses.     

Indications for Pericardial Glutaraldehyde-Preserved Xenograft in Repair of Congenital Heart Disease

A glutaraldehyde-preserved equine pericardial xenograft was implanted in 370 patients between 1981 and 1987; pericardial sac closure in 320 (mainly over Dacron implants), atrial repairs in 19, arterial reconstructions in 22 (right outflow tract in 19, Konno's procedure in three), control of bleeding after surgery for thoracic aneurysms in seven, control of plasma leaking PTFE graft in one, and repair of diaphragmal agenesia in one. Overall infection rate was 3/370 (0.8%). Epicardial adhesions (12) at reoperation for orthotopical implants were graded 1.3 +/- 0.9 on a scale of 6 (0 = no adhesions, 5 = calcified or ossified adhesions) after 4 +/- 2 months. Shrinkage of xenograft occurred in 3/19 (16%) atrial repairs and lesser degree aneurysmal dilatation appeared in 1/19 (5%) reconstructions of the right outflow tract. No complications occurred in the implants without direct exposure to the blood stream. We recommend pericardial xenograft for Konno's procedure and control of bleeding. It should not be used routinely in the low pressure side.     

Efficacy of a hyaluronan derivative gel in postsurgical adhesion prevention in the presence of inadequate hemostasis.

BACKGROUND: We previously demonstrated that an auto-cross-linked hyaluronan-based antiadhesion agent (auto-cross-linked polysaccharide [ACP] gel) was effective in postsurgical adhesion prevention after open laparotomy and laparoscopic surgery with adequate hemostasis in animal models. This study assessed the ability of different preparations of ACP gel to prevent adhesions in the presence of bleeding or inadequate hemostasis. METHODS: Ninety-seven female rabbits were subjected to a standardized surgical lesion with subsequent exudative abdominal bleeding (oozing model), and 97 animals were subjected to a standardized surgical lesion with severe abdominal bleeding (bleeding model). After injury, the animals were randomly assigned to 5 groups of treatment: 3 different preparations of ACP gel (20, 40, and 60 mg/mL), a hyaluronan-carboxymethylcellulose film, and no treatment. Three weeks after operation, the animals were killed, and the adhesions were assessed by a blinded observer who measured the length and area of the adhesions and who used the Blauer scoring system. RESULTS: All 3 preparations of ACP gel and the hyaluronan-carboxymethylcellulose film reduced adhesion formation in both models (P <.01) as measured by the number of adhesion-free animals, mean Blauer score, and the mean length and surface area of the adhesions. There were no statistical differences between the different treatment groups. CONCLUSIONS: These data suggest that different hyaluronan based agents in the presence of severe bleeding or exudative abdominal bleeding reduce de-novo postsurgical adhesion formation.     

Tropical application of halcinonide cream reduces the severity and incidence of intraperitoneal adhesions in a rat model

BACKGROUND: Systemic or intraperitoneal administration of corticosteroids has been reported to have conflicting effects on the prevention of peritoneal adhesions. Painting corticosteroid cream directly on the likely site of adhesion formation, owing to its high concentrations and persistent effects, may be a promising approach to prevent peritoneal adhesion formation. METHODS: Adhesions were induced by abrading of the cecum, followed by dropping of 95% ethanol. Sixty Wistar rats were randomly allocated to two control groups with no further treatment of the cecum and to two therapy groups treated with 0.1% halcinonide cream painted directly on the damaged surface of the cecum. After 3 and 7 days, adhesion scores, adhesion incidence, and intraperitoneal leukocytes were evaluated. RESULTS: On both postoperative days 3 and 7, halcinonide cream resulted in a significant decrease in mean adhesion scores (6.80 versus 0.67, 10.40 versus 1.26; P <0.001, P <0.001, respectively). The adhesion incidence was 43.3% for the therapy groups and 100% for controls (P <0.01). On day 3, the total numbers of intraperitoneal leukocytes were 120.73 +/- 24.01 millions for the therapy groups and 270.40 +/- 34.68 for controls (P <0.001). CONCLUSIONS: Painting halcinonide cream directly on the damaged surface of the cecum could effectively reduce the severity and incidence of adhesion, possibly by suppression of early inflammatory exudate and of late fibroblast invasion and proliferation.     

Modified rapid deployment hemostat bandage reduces blood loss and mortality in coagulopathic pigs with severe liver injury

BACKGROUND: Hemostasis can be difficult to achieve after blunt abdominal trauma, especially if the patient is coagulopathic. The U.S. Food and Drug Administration has recently approved a hemostatic dressing for treating bleeding after extremity trauma (RDH bandage; Marine Polymer Technologies, Cambridge, MA). It has not been evaluated for internal bleeding after trauma. We redesigned this dressing for internal use, and then tested whether this modified bandage (Miami-modified Rapid Deployment Hemostat) could achieve hemostasis when used as an adjunct to standard laparotomy pad packing in a pig model of severe liver injury with coagulopathy. METHODS: Anesthetized swine (35-45 kg) received an isovolemic 45% blood volume replacement with refrigerated Hextend (6% hetastarch). Core body temperature was maintained at 33-34 degrees C with intra-abdominal ice packs. A coagulopathic condition was documented by thromboelastography. At this point a severe liver injury was induced by the avulsion of the left lateral hepatic lobe, then the pigs were randomized to treatment with either standard abdominal packing (control) or packing plus Miami-modified Rapid Deployment Hemostat. Two series of experiments were conducted. In series one (n = 14), the abdomen was closed and the animals were observed with no resuscitation. After one hour, the abdomen was opened, the packing was removed and the presence of bleeding was noted. In series two (n = 10), the abdomen was closed and the animal resuscitated with one unit of blood plus as much lactated Ringers intravenous fluid (IVF) as required to maintain a mean arterial pressure (MAP) > 70 mm Hg. After one hour, the packing was removed, the abdomen closed, and data were collected for an additional two hours. RESULTS: Series one: 6/7 animals in the control group had continued bleeding at one hour; 1/7 animals in the treatment group had active bleeding (p = 0.0291). Series two: With control vs. Miami-modified Rapid Deployment Hemostat, the three-hour survival was zero vs. 80% (p = 0.0476). The total blood loss was 1.2 +/- 0.1 vs. 0.3 +/- 0.1 mL/kg/min (p = 0.001) and the IVF requirement was 1.6 +/- 0.3 vs. 0.6 +/- 0.3 mL/kg/min (p = 0.026). CONCLUSIONS: The Miami-modified Rapid Deployment Hemostat bandage significantly reduced mortality, blood loss, and fluid requirements when used as an adjunct to standard abdominal packing following severe liver injury in coagulopathic pigs [corrected].     

Prospective comparison between total sternotomy and ministernotomy for aortic valve replacement

Ministernotomy (MS) is an alternative for total sternotomy (TS) in aortic valve replacement. We compared these two approaches for results and adverse effects in a prospective study. From January to December 2000, 100 patients who underwent aortic valve replacement were included in two groups of 50 according to the surgical approach that used MS or TS; one senior surgeon performed all cases in each group. Valvular pathologies were either stenosis or insufficiency. Mean age was 63 +/- 14 years in MS, 67 +/- 12 in TS (p = ns). NYHA class was 2.7 +/- 0.5 in MS, 2.8 +/- 0.6 in TS (p = ns). Left ventricular ejection fraction was 58 +/- 12% in MS, 57 +/- 12% in TS (p = ns). There was a significant difference between MS and TS in aortic cross-clamping (66 +/- 14 min vs 48 +/- 9 min) and cardiopulmonary bypass (88 +/- 18 min vs 69 +/- 10 min, p < 0.01), but not in intervention times (2.8 +/- 0.4 hours vs 2.7 +/- 0.4 hours). Mean intensive care stay was reduced in MS (1.7 +/- 1.6 days vs 2.6 +/- 6 days, p < 0.05). Intubation times (12 +/- 7 hours vs 14 +/- 9 hours), 24 hours bleeding (394 +/- 219 mL vs 465 +/- 318), reintervention for hemostasis (4% vs 2%), rhythmic complications (14% vs 14%), and mortality at 1 month (2% vs 2%) were comparable in MS and TS. In aortic valve surgery, ministernotomy is technically more demanding and needs more time. It is as safe and as effective as conventional sternotomy but its eventual benefits, excepting upon cosmesis, are still to be defined.     

Comparison of adhesion reformation after laparoscopic and conventional adhesiolysis in an animal model

This study set out to compare adhesion reformation after conventional and laparoscopic adhesiolysis using two different laparoscopic dissection techniques. In a first operation, 36 rabbits underwent fixation of 6 cm2 of the cecum with the serosa removed to the lateral abdominal wall to induce standardized adhesions. After 4 weeks, adhesiolysis was performed laparoscopically (n = 12) or via laparotomy (n = 12) using sharp and blunt dissection. In a third group (n = 12), laparoscopic adhesiolysis was performed using monopolar electrocautery. Outcome was assessed by incidence, extent, and localization of adhesion reformation. After conventional adhesiolysis, all rabbits developed new adhesions relative to 79% after laparoscopic adhesiolysis. The extent of reformed adhesions (median) was greater after conventional adhesiolysis than laparoscopic adhesiolysis (2725 mm2 vs 230 mm2, P < 0.001). The latter did not differ significantly from laparoscopic adhesiolysis by electrocautery (310 mm2). There were small adhesions to 3 of 72 trocar wounds, but extensive adhesions to 33% of the abdominal incisions were found in the conventional group. In this standardized experimental setting, laparoscopic adhesiolysis is associated with a significantly reduced reformation of adhesions. Different laparoscopic dissection techniques have no significant influence on the extent of adhesion reformation.     

Influence of hematocrit on hemostasis in continuous venovenous hemofiltration during acute renal failure

BACKGROUND: Hematocrit plays a major role in primary hemostasis by influencing blood viscosity and platelet adhesion. During continuous venovenous hemofiltration (CVVH), it is suspected that an increased hematocrit is accompanied by an activation of hemostasis and frequently leads to thromboses in the extracorporeal system. In order to examine this hypothesis, we studied the influence of hematocrit on hemostasis during CVVH. METHODS: Fourteen patients (8 men and 6 women, mean age 65+/-10 years) with acute renal failure undergoing CVVH were prospectively enrolled. Polysulfone hemofilters (AV 600; Fresenius, Oberursel, Germany) were used in all of the patients; blood flow rates were adjusted to 120 ml/min. No blood products and coagulation-related medication, except unfractionated heparin, were applied. Study exclusion criteria included a history of thromboembolism and artificial heart valves. Hemostasis activation markers (fibrinopeptide A, thrombin-antithrombin III complex, beta-thromboglobulin, platelet retention) and hematocrit values were determined before and at three-day intervals during the course of CVVH treatment. RESULTS: The mean hematocrit value (mean +/- SEM) was 29+/-1% (range, 22 to 35%). Patients with hematocrit values of less than 30% (N = 7) were compared with patients with higher hematocrit values (>30%, N = 7). The patients with a lower hematocrit (<30%) showed a stronger activation of hemostasis during CVVH when compared with those with a higher hematocrit (>30%), as indicated by a tendency toward higher values for fibrinopeptide A (25+/-8 vs. 14+/-5 ng/ml, P = 0.35), thrombin-antithrombin III complex (15+/-4 vs. 10+/-2 ng/ml, P = 0.66), and a higher beta-thromboglobulin/creatinine ratio (0.62+/-0.17 vs. 0.48+/-0.12, P = 0.8). CONCLUSION: Contrary to our hypothesis, hematocrit values of more than 30% are not accompanied by an increased hemostasis activation during CVVH. Concerning hemostasis activation, hematocrit values between 30 and 35% may be suitable for patients on CVVH.     

Effect of a composite membrane of chitosan and poloxamer gel on postoperative adhesive interactions

Excessive postoperative adhesion formation is a major result of surgery. The adhesion reduction effects of a chitosan membrane and poloxamer gel barrier were measured in a rat peritoneal model. Forty-four male Sprague-Dawley rats were divided into four groups (control, poloxamer, chitosan, and poloxamer+chitosan sandwich). Two cm2 of cecal serosa and the adjacent abdominal wall were abraded. The denuded cecum was covered with either a chitosan membrane, a poloxamer gel, chitosan in a sandwich configuration with poloxamer on both sides, or neither (control group) and apposed to the abdominal wall. Fourteen days after surgery adhesions were graded using a whole-number scoring system of zero to five. Adhesion strength was determined using a whole-number system of one to four. Adhesion area was measured on a continuous scale of adhesion severity. Adhesion grades were highest in the control group (5.00 +/- 0.00) and were significantly (P < 0.05) lower in the poloxamer group (3.50 +/- 1.35), the chitosan group (1.64 +/- 1.63), and the poloxamer+chitosan group (1.18 +/- 1.25). The two chitosan-containing groups also had significantly (P < 0.05) reduced adhesion grades in comparison with the poloxamer group. Adhesion area in both chitosan-containing groups was reduced in comparison with control and adhesion strength was reduced significantly (P < 0.05) in all groups compared with control. The poloxamer+chitosan group had significantly (P < 0.05) reduced adhesion strength versus poloxamer only. There was a significant (P < 0.05) linear correlation (r = 0.931, P < 0.001) between adhesion grade and adhesion strength. We conclude that chitosan and the combination of poloxamer+chitosan were shown to effectively reduce adhesion area, grade, and strength.     

Role of laparoscopy in identifying the clinical significance and cause of adhesions and chronic pelvic pain: a retrospective review at the Kiel School of Gynecological Endoscopy.

OBJECTIVES: We sought to define the role of laparoscopy in identifying the clinical significance, cause, and association between adhesions and chronic pelvic pain. METHODS: A retrospective chart review was conducted from October 2004 to July 2005, at the Kiel School of Gynecological Endoscopy, University Hospitals Schleswig-Holstein, Campus Kiel, Germany. Included in the study was the analysis of 462 laparoscopic procedures; 275 (59.5%) of the patients undergoing these procedures had pelvic or abdominal adhesions. Of these, 84 (30.5%) patients were admitted with the main complaint of chronic pelvic pain. Further evaluation and assessment of this group was carried out. RESULTS: Among those patients with adhesions, the second most frequent reason for admission was chronic pelvic pain (30.5%) (P<0.0005). In our study, adhesions were found in 79.2% (n=84) of patients (n=106) with chronic pelvic pain. These adhesions were thin-filmy (19.0%) or thick-fibrous (81.0%) adhesions containing blood vessels. Thick-fibrous adhesions were present in 50.0% of patients at multiple abdominopelvic sites (P<0.005). CONCLUSIONS: Thick-fibrous adhesions that extend beyond the pelvic sidewall can cause significant chronic abdominopelvic pain.     

Attenuating effects of chymase inhibitor on pericardial adhesion following cardiac surgery

OBJECTIVE: Chymase, a serine protease, is released from mast cells, which is closely associated with adhesion formation. Chymase activates transforming growth factor-beta1 (TGF-beta1), which promotes tissue fibrosis. Recently we have found that chymase may play an important role in adhesion formation in hamsters. Accordingly, this study was designed to confirm that a chymase inhibitor prevents postoperative cardiac adhesions in large animals. METHODS: In 14 dogs, the epicardium was abraded 200 times with gauze and the mid-portion of the left anterior descending coronary artery (LAD) was exposed with No. 15 blade. Either chymase inhibitor (CI group, n = 7) or placebo (P group, n = 7) was sprayed into the pericardial cavity, then the pericardium was closed. Cardiac chymase activity, the level of TGF-beta1 in the pericardial fluid, the density of epicardial mast cells, the adhesion area between the heart and the pericardium, and the presence of adhesion between the mid-LAD and the pericardium were evaluated 1 and 2 months after surgery. Five nonsurgical dogs were used as a control for cardiac chymase activity. RESULTS: Cardiac chymase activity and TGF-beta1 level were lower in CI group than in P group (53.7 +/- 35.0 vs. 93.4 +/- 20.4 microU/mg protein, p = 0.01, 3.2 +/- 0.9 vs. 4.3 +/- 1.1 microg/mL, p = 0.06, respectively). In CI group, the density of mast cells (19 +/- 5 vs. 32 +/- 8 cells/cm, p < 0.01), the adhesion area (2.2 +/- 0.8 vs. 7.5 +/- 1.5 cm2, p < 0.01), and adhesions between the heart and the mid-LAD (0% vs. 57%) were all reduced. CONCLUSION: Chymase inhibitor suppresses cardiac chymase activity and reduces the TGF-beta1 level, resulting in a reduction of cardiac adhesion in a large animal.     

Heparin-bonded cardiopulmonary bypass circuits reduce bleeding and transfusion requirements in proximal aortic surgery.

BACKGROUND: Methods to improve hemostasis in aortic surgery continue to evolve. Use of heparin-bonded cardiopulmonary bypass circuits (HBC) has been shown previously to effectively reduce bleeding and improve outcomes in coronary and valve operations. OBJECTIVE: To evaluate the impact of HBC on bleeding and transfusion requirements in proximal aortic surgery. METHODS: Data on 140 consecutive patients undergoing 144 operations of the proximal aorta were collected. Between July 1987 and July 1994, conventional cardiopulmonary bypass circuits (CONV) were used (n = 53). In July 1994, we switched to "tip-to-tip" HBC (n = 91). This study compared clinical outcomes and transfusion requirements between these two groups. RESULTS: Indications for surgery, baseline characteristics, and operative profile of the study groups were similar. Overall operative mortality and reoperation for bleeding were 9% and 13%, respectively. Compared with CONV, use of HBC was associated with decreased mortality (3% vs 18%, p = 0.004), reoperation for bleeding (7% vs 24%, p = 0.005), and hospital length of hospital stay (10 +/- 11 vs 20 +/- 30 days, p = 0.002). Although the incidence of allogeneic blood transfusion was similar (HBC 75% vs CONV 87%, p = 0.12), the magnitude of blood products utilization was much lower in the HBC group (total blood products per patient: 24 +/- 29 vs 49 +/- 47 donor units, p = 0.0002). In the multivariate analyses, use of HBC was identified as an independent predictor of reduced mortality, morbidity, and reduced magnitude of allogeneic blood transfusions. CONCLUSION: Use of HBC in proximal aortic surgery resulted in reduced bleeding and blood transfusion, improving clinical outcomes. Undoubtedly, multiple factors account for the overall improved results. However, use of HBC is an important component of an overall blood conservation strategy.     

Reduction in postoperative adhesion formation and re-formation after an abdominal operation with the use of N, O - carboxymethyl chitosan

BACKGROUND: Postoperative adhesions have proven to be intractable complications after abdominal operations. This study assessed the efficacy of N, O - carboxymethyl chitosan (NOCC) to limit adhesion formation and re-formation in a rabbit abdominal surgery model. METHODS: In study 1 (adhesion formation), injuries to the large bowel, cecum, and abdominal sidewall were generated in rabbits. The rabbits (10/group) were randomly assigned to 1 of 5 treatment groups: Group A received no NOCC treatment; in group B, NOCC gel was applied directly to the injured site and NOCC solution was applied throughout the abdominal cavity; in group C, NOCC gel was applied near the injured site and NOCC solution was applied as above; in group D, NOCC gel was applied distant to the injury and NOCC solution was applied as above; in group E, a mixture of NOCC gel and solution was applied at the injured site. Adhesions were evaluated 14 days later. In study 2 (adhesion re-formation), adhesions were generated as above but were then lysed by careful dissection. After adhesiolysis, the rabbits (9/group) were treated with NOCC gel and solution at the site of adhesiolysis or left untreated. Adhesion re-formation was assessed 14 days later. In study 3 (mechanism of action), sterile tissue culture plates were coated with NOCC and adhesion of cultured, radiolabeled murine fibroblasts to the plates was assessed. RESULTS: In study 1, animals treated with NOCC gel and solution showed reduced adhesion formation (P<.01). NOCC gel was equally efficacious if applied on the site of injury or near the site of injury but less efficacious if applied at a site distant to the injury. In study 2, animals treated with NOCC gel and solution showed less adhesion re-formation compared with the untreated control animals (P<.01). In study 3, murine fibroblasts did not adhere to NOCC-coated tissue culture plates. CONCLUSIONS: NOCC gel and solution can reduce adhesion formation and re-formation in this rabbit model. The inability of fibroblasts to adhere to NOCC solution-coated surfaces suggests that NOCC may act as a biophysical barrier.