About Authors:
1Robin Sharma*, 1Ajay Kumar, 2Dr. Bharat Prashar
1M.Pharm (Pharmacology)
2Head of Pharmacy Department
Manav Bharti University, Solan.
*sharmarobin@hotmail.com
ABSTRACT
Postoperative adhesions are a significant health problem with major implications on quality of life, health care and expenses on treatment. The purpose of this review was to investigate the incidence of post operative adhesions and the treatment measures such as efficacy of preventative techniques and adhesion barriers. The National Library of Medicine, Medline and A-Z databases were used to identify articles related to postoperative adhesions. Ileal pouch–anal anastomosis, open colectomy, and open gynecologic procedures are associated with the highest risk of adhesive small-bowel obstruction (class I evidence). Based on expert opinion (class III evidence) intraoperative preventative principles, such as meticulous haemostasis, avoiding excessive tissue dissection and ischemia, and reducing remaining surgical material such as powdered gloves have been published. Laparoscopic techniques, result in fewer adhesions than laparotomy techniques (class I evidence). Available bioabsorbable barriers, such as hyaluronic acid/carboxymethylcellulose, have been shown to reduce adhesions (class I evidence). Postoperative adhesions are a significant health problem after the surgery. General intraoperative preventative techniques, laparoscopic techniques, and the use of bioabsorbable mechanical barriers in the appropriate cases reduce the incidence and severity of peritoneal adhesions and post operative adhesions.
Reference Id: PHARMATUTOR-ART-1435
Introduction
Adhesions are fibrous bands that connect anatomic sites at locations where there should not be connections. Post-operative adhesions account for more than 90% of the total intra-abdominal adhesions [1-9]. The development of post-operative adhesions after upper and lower abdominal surgery is part of the daily life of every digestive surgeon. Despite this, there are very few good quality longitudinal studies that permit an appreciation of the frequency of adhesion formation or of adhesion-related complications. Meanwhile post-operative adhesions are the cause of considerable direct and indirect morbidity, and their prevention can be considered a major public health issue. And yet, in France at this time, there is no validated recommendation neither concerning the prevention of adhesions, more particularly, concerning the use of a variety of commercial anti-adhesion products that have been marketed for at least a decade. Intraperitoneal adhesions develop between deperitonealized surfaces of abdominal organs, mesenteries, and the abdominal wall; the most common site of adhesion formation is between the greater omentum and the anterior abdominal wall [10,11]. Despite the frequency of adhesions and their direct and indirect consequences, there is only one published recommendation (from the gynecologic literature) concerning the prevention of peritoneal adhesions [12]. Faced with a very heterogeneous literature, it was proposed that a working group review the literature and provide answers to four questions:
· What factors contribute to the formation of adhesions? (pathophysiology, types of interventions);
· What is the incidence of post-operative adhesions? (after upper or lower abdominal surgery, after laparotomy or laparoscopy);
· What are the medical and surgical consequences of post-operative adhesion formation? (direct and indirect consequences);
· What measures are available to prevent post-operative adhesions? (surgical technique and pharmacologic methods)
Incidence of adhesions
An assessment of how many people develop adhesions after surgery was performed in a post-mortem series by Weibel and Majno in 1973 [13]. In cadavers with no preceding abdominal surgery, adhesions were found in 28%, and in those that had had abdominal surgery 67% had adhesions. Where minor abdominal surgery had been performed, adhesions were present in about 50%. If major surgery had been undertaken adhesions were present in 76%, and in cases of multiple abdominal surgery 93% had adhesions present. The incidence of adhesions in a live population has been examined [10]. Inflammatory adhesions in patients who had not undergone any preceding abdominal surgery were found to be present in 10%. In patients who had had previous abdominal surgery, postoperative adhesions were found in 93% and inflammatory adhesions in 20%. Congenital adhesions were identified in less than 1%. The difference in the incidence of adhesions between the two studies is due to a difference in the age groups between the post-mortem and live studies. In the post-mortem study inflammatory adhesions were rarely seen in those under the age of 60 years. The mean age of patients without earlier abdominal surgery in the live study was 63 years. In patients who had had surgery the mean age was 75 years and therefore they were far more likely to have had intra-abdominal inflammatory episodes that resulted in adhesions, such as cholecystitis and diverticulitis.
Economical Burden of Adhesions
Problem associated with post operative adhesions pose a significant financial burden as they increase the surgical work load and utilize limited health resources [14]. Awareness concerning economical consequences resulting from adhesions is rising [15]. A Swedish study estimated the cost incurred for total care, including sick leave expenditure, for adhesive small bowel obstruction was at least US $ 20 million a year. Another study in United States looked at 1988 cases of abdominal adhesions associated complications and found that hospitalization and treatment cost was up to US $ 1.2 billion [16]. These studies did not include out patients and indirect cost such as loss of function due to long term disabilities. Although these added costs due to adhesions do not apply to cardiac surgery, they are very evident in other specialities such as general surgery.
Physiology and Physiopathology
The mechanism of adhesion formation is largely due to insufficient fibrinolysis at the site of visceral or parietal peritoneal injury resulting in incomplete resorption of local fibrinous deposits [17,18]. Thus, post-operative adhesions are the consequence of abnormal peritoneal cicatrisation: the lack of early post-operative fibrinolysis (in the first 48 hours) allows cellular infiltration of the initial fibrinous matrix. This leads to the formation of adhesions that, by the seventh day, are composed of an extracellular collagenous matrix infiltrated by fibroblasts (occasionally associated with painful nerve endings), smooth muscle cells, and neovascularization; this assemblage is coated with a mesothelial lining. Technical operative factors resulting in tissue trauma (electrocoagulation, ultrasonic tissue transection, laser energy versus sharp dissection with scissor and scalpel) [19,20] as well as residual microscopic or larger foreign bodies are determining risk factors for adhesion formation [21].
Intra-abdominal infections with inflammation and radiation tissue damage also contribute to adhesion formation. Finally, the presence of hemoperitoneum seems to potentiate adhesion formation in conjunction with the above-mentioned factors.
Figure 1 : A schematic illustration of process in adhesion formation.
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Incidence of Postoperative Adhesions
The frequency of peritoneal adhesion formation after abdominal surgery is difficult to assess due to the lack of studies with a high-level of evidence on this subject.
Frequency of post-operative adhesions after upper abdominal surgery
According to available data, peritoneal adhesions form in 93-100% of cases after laparotomy for upper abdominal surgery in adults [10-11]. The laparoscopic approach would seem to decrease the risk to 45% [11]. The frequency of surgical re-intervention for adhesion-related symptoms varies with the type of initial procedure but, in all cases, remains below 10% in adult patients [10] between 6.4 and 10% [22-24]. The greater omentum is the organ most typically involved by adhesion formation [10].
Frequency of symptomatic post-operative adhesions after lower abdominal surgery
An analysis of the frequency of symptomatic adhesions is not possible at present except by analysis of long-term postlaparotomy complications.
Surgery by open laparotomy
After lower abdominal open surgery, 67-93% of patientsdevelop adhesions [10,25], but only 5-18% of these casesbecome symptomatic (bowel obstructions). The rate ofsymptomatic complications varies depending on the type ofinitial operation and the duration of post operative follow-up.The rate of complications directly related to adhesionsresulting in one or more hospitalizations is 3.8% [25-33].The most common site of adhesion formation is betweenthe greater omentum and the midline closure, but theseadhesions rarely result in bowel obstruction unless the bowelwall itself is involved [10]. Risk factors for the developmentof symptomatic adhesions include the number of previousinterventions, a history of peritonitis, and age less than 60years [26].
Laparoscopic surgery
No data with high-level evidence are available in this context. The frequency of symptomatic adhesions requiring re-intervention after lower abdominal laparoscopic surgery has been evaluated at 2% after colorectal surgery (whether for benign or for malignant disease) at 2.8% after rectal surgery (benign or malignant), and at 0.76% after appendectomy [34-37]. The long-term incidence of adhesion-related post-operative obstruction has been measured in two randomized prospective studies comparing laparoscopy versus laparotomy for colorectal surgery. These studies showed no statistically significant difference in the rate of postoperative obstruction: 5.1% versus 6.5% in the study by Scholin et al., and 2.5% versus 3.1% in the study by Taylor et al. The highest rate of post-operative obstruction was seen in the group of patients who required conversion from laparoscopy to laparotomy (6%) [38].
Medical and surgical consequences of peritoneal adhesions
Adhesions are responsible for direct complications (acute intestinal obstruction, chronic abdominal pain, infertility) and for indirect complications encountered at surgical re-interventions (difficult dissection, prolonged operative time, intra- and post-operative complications).
Direct consequences
There are multiple direct of adhesions with serious potential complications.
Acute intestinal obstruction
Peritoneal adhesions are the underlying cause of 32% of acute intestinal obstructions and of 65%-75% of small bowel obstructions. (SBO) This complication accounts for 2.6-3.3% of all indications for laparotomy [10,30-47]. The number of previous abdominal surgeries increased the development of peritoneal adhesions. The interval between the initial abdominal surgery and the first episode of acute small bowel obstruction varies enormously from eight days to 60 years with a mean interval of 3.7-8.9 years [10,30-47]. The need to resect intestine during re-intervention for small bowel obstruction varies from 5.7-23.2% [39]. The greatest risk of this complication seems to occur after previous colorectal surgery, which is fraught with risks of more complex adhesion formation. Recurrent complications of adhesions occur frequently after surgery for acute bowel obstruction (12-19%). The identified risk factors for acute intestinal obstruction were: age under 40 years, a complicated post-operative course, the type of adhesions (complex), multiple (>3) previous abdominal surgeries, and conservative treatment of a previous acute small bowel obstruction [41]. It seems that the first episode of acute small bowel obstruction occurs in 3/4 cases after one or two abdominal surgery [41]. However, the increase of peritoneal adhesions based on the number of surgical procedures, does not correlate in proportion to the risk of bowel obstruction. The post-operative mortality related to surgery to relieve adhesion-related acute small bowel obstruction was estimated at less than 10%. The pre- and post-operative risk factors for mortality included: ASA score greater or equal to 3, age above 75 years, the presence of dyspnea at rest, renal insufficiency, hemoconcentration/dehydration, the type of obstruction (mechanical + strangulation), intraoperative complications (intestinal spillage with peritoneal contamination), and post-operative medical complications. Surprisingly, the need for intestinal resection did not appear as a risk factor for mortality [47,48]. The post-operative morbidity for adhesion-related acute SBO is estimated at 13—47%. Risk factors for morbidity include: ASA greater or equal to 3, age above 80 years, poor general condition for independent living, past history of cardiac insufficiency, previous stroke with neurological deficit, chronic obstructive pulmonary disease (COPD), leukopenia (WBC <4500/mm3), creatinine more than 1.2 mg/dL, the type of previous surgery (intestinal resection vs. adhesiolysis), infected or contaminated operative field, more than ten adhesions, and failure to perform enterectomy after a bowel injury [47,48]. The most frequent complications were: pneumonia/atelectasis (17%), prolonged ileus more than seven days (16%), inability to wean from ventilator within 48 hours (13%), need for endotracheal re-intubation (9%), wound infection (9%), abdominal wall abscess and/or evisceration (more common after enterectomy) [47,48].
Post-operative chronic abdominal pain
Post-operative pain due to adhesions is a controversial entity; its definition remains imprecise and is often not specified in the numerous studies on this subject. Its actual incidence is therefore unknown. Laparoscopy has both a diagnostic and therapeutic role since it permits recognition and simultaneous treatment of the cause of pain, although adhesiolysis may result in renewed adhesion formation. In any case, the benefit of extensive adhesiolysis in the treatment of patients with chronic abdominal pain and diffuse adhesions has not been proved, and this procedure has its own significant morbidity (enterotomy) [49]. On the other hand, chronic abdominal pain frequently recurs, even after an initial period of improvement.
Indirect consequences of intestinal adhesions during surgical re-interventions
The presence of abdominal adhesions increases operative time, particularly when the operative site of interest has already been dissected. Adhesions lead to increased intra-operative morbidity due mainly to intestinal wounds. Intestinal injuries occur in from 0.06% to 19% of cases and are the cause of increased post-operative morbidity (fistula, intestinal obstruction, wound abscess, respiratory complications) [50,51]. The number of previous laparotomies, and obesity (BMI > 25 kg/m2) were risk factors for intestinal injury. The laparoscopic approach seems to be associated with a delay in recognition of intestinal perforation [52-57]. The laparoscopic approach to adhesiolysis also seems to directly increase the incidence of this complication, particularly due to accidents of trocar placement that are responsible for 40% of such injuries. If bowel injury is recognized intra-operatively, conversion to laparotomy is often necessary. The risks related to conversion are highly variable depending on the type of procedure performed (3.3-100%). There are few reports of hemorrhagic complications due to adhesiolysis. The need for post-operative transfusion is higher in patients who have had previous laparotomy [58]; they are considerably higher if the surgery addresses an abdominal site that had been previously dissected. For all these reasons, it is important that patients be informed of an increased risk of surgical complications associated with previous surgery and postoperative adhesions.
Prevention
In view of the magnitude of the medical problems and financial burden related to adhesions, prevention or reduction of postoperative adhesions in an important priority. Some groups have recognized the importance of the problem and have attempted to educate physicians on this issue. Numerous articles on adhesion barriers have been published but several controversies such as the effectiveness of available agents and their indication in general surgical patients still exist. Most of the available literature is based on gynecologic patients. For general surgical patients no recommendations or guidelines exist. Any prevention strategy should be safe, effective, practical, and cost effective. A combination of prevention strategies might be more effective but our knowledge on this topic is fairly limited. The prevention strategies can be grouped into 4 categories: general principles, surgical techniques, mechanical barriers, and chemical agents.
Adhesion control
Clinically, there is no means of completely preventing adhesion formation. Two commonly used solutions in clinical practice that have some anti-adhesion effect in the laboratory animal are povidone-iodine [59] and 32% dextran 70 [60]. Povidone-iodine is popular among some general surgeons as a peritoneal lavage, more for the antimicrobial effect than the anti-adhesion properties. Dextran is often used by gynaecological surgeons for adhesion prevention in infertility surgery and there is some clinical evidence that it has some effect in these cases [61]. Independent of adjuvant therapy for the prevention of adhesion formation, there are several operative steps that can be taken to reduce the extent of adhesion formation and to minimise the chances of subsequent adhesive obstruction:
1. Handle the bowel carefully to reduce serosal trauma.
2. Avoid unnecessary dissection.
3. Exclude foreign material from the peritoneum, e.g. use absorbable ligatures and sutures where possible, preferably those that are hydrolysed rather than phagocytosed. If non absorbable material is to be used then keep the cut ends as short as possible. Avoid excessive use of gauze swabs. Wear starch free gloves.
4. Adequately excise ischaemic or infected debris within the peritoneum.
5. Preserve the omentum, if possible. Place the omentum around the site of surgery and run the omentum under the wound to encourage low-risk adhesions to form.
6. Avoid the division of adhesions that do not involve the small bowel.
By what means we can prevent post-operative adhesions?
Technical means
Any surgical technique that can reduce visceral and peritoneal traumatic injury is considered a priori potentially beneficial in the prevention of adhesions.
Two methods devolving from this principle are:
· Surgery should be performed with the most atraumatic technique possible [62,63]. The measures which seem most useful to prevent the risk of adhesions include: gentle manipulation of tissue, meticulous hemostasis, the choice of small caliber sutures of inert composition, frequent irrigation of the area of dissection to prevent the formation of fibrinous deposits, minimal use of monopolar electrocautery to prevent diffuse thermal injury, maximal resection of devitalized tissues, removal of fibrinous residues and blood clot prior to peritoneal closure;
· Laparoscopy: the theoretic advantages of this approach include: minimal incision of the parietal peritoneum, a maximal reduction of microscopic foreign bodies, preservation of the moist closed intraperitoneal environment, decreased bleeding and more precise dissection (particularly for pelvic and rectal surgery), and the absence or minimization of manipulation beyond the operative zone; these advantages have been highlighted in several retrospective studies comparing laparotomy and laparoscopy [63-65], but the level of evidence is low in these studies. The theoretical advantages have not been shown to translate into a decreased risk of bowel obstruction in two randomized prospective studies comparing the long-term risk of bowel obstruction after colorectal surgery by the laparotomy or laparoscopic approach [38,66]. These contradictory results suggest that a decrease in abdominal adhesions does not necessarily result in a decrease in the rate of post-operative obstruction.
Commercial products and devices to prevent adhesion formation
The mechanisms of action of anti-adhesion products are based on two principles: hydroflotation and the barrier phenomenon.
Hydroflotation
It is the mechanism of action of products instilled into the peritoneal cavity. These are fluids such as a 4% solution of Icodextrin. Their principal theoretical advantage is that the product is applied to the entire peritoneal surface and is easy to use in the laparoscopic setting. Disadvantages include: the kinetics of peritoneal reabsorption are variable from patient to patient, but reabsorption is often complete within one to two days while the histopathologic process of adhesion formation continues throughout the first postoperative week, and the fluid tends to accumulate in the pelvis and pouch of Douglas as the patient changes position [62]. At this time, these products do not have marketing approval in France for gastrointestinal surgery indications.
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The barrier phenomenon
It is the preponderant mechanism of action of a variety of products marketed as biocompatible and biodegradable films, such as membrane films of hyaluronic acid on a supporting structure of carboxymethylcellulose (Seprafilm®, Genzyme Corp., USA), oxidized cellulose (Interceed®, Johnson& Johnson, New Brunswick, NJ, USA), and in the form of inert non-resorbable prostheses such as expanded polytetrafluoroethylene patches (PTFE) (Gore-Tex® and Preclude®, Gore & associates, Newark, Delaware, USA). Their principal advantage is to set up a fixed physical barrier between the viscera from the parietal peritoneum, whose reabsorption kinetics can be much better controlled and predictable than is the case for solutions and gels. Their principal disadvantage is that their action is limited only to the site where they are placed. A single leaf of these products covers only a small percentage of the total peritoneal surface; the surgeon must be mindful that it only requires a single adhesion (that may develop at some distance from the operative site) to provoke a severe complication such as bowel obstruction [62]. The surgeon must therefore select the zone for film application where he anticipates the greatest likelihood of adhesion formation; surgeons usually opt for the incision line and the site of surgical dissection. A second disadvantage is that films are technically difficult to apply through laparoscopic access ports. This is particularly the case for Seprafilm® [67]; it is extremely difficult to achieve accurate placement of Seprafilm® at laparoscopy, and yet the effect of the treatment depends essentially on impeccably accurate placement. For placement of nonresorbable patches (expanded PTFE) that require suture fixation, laparoscopic placement is even more difficult. Products in gel form depend of both hydroflotation and the barrier phenomenon for their effect; these include 0.5% ferric hyaluronate gel (Intergel®, Lifecore Biomedical Inc, Chaska, MN, USA) and a hydrogel of polyethylene glycol delivered as a spray (Spraygel®, Confluent Surgical Inc, Waltham, MA, USA), or a derivative with more rapid resorption and neutral coloration (Sprayshield® Covidien,Waltham, MA, USA). The advantages of gel anti-adhesion products are a longer half-life (one to two weeks) than instilled peritoneal liquids, and ease of application compared to film placement, particularly when applied to irregular surfaces such as the limbs of enteric anastomoses.
Bioabsorbable gels
Various agents have been developed and tested, but most have been abandoned or withdrawn because of safety issues or a lack of efficacy. SprayGel (Confluent Surgical, Inc, Waltham, MA) is one of the more extensively tested gels. It is a sprayable hydrogel that adheres to the tissues for a period of 5 to 7 days. After several days it is hydrolyzed into water-soluble molecules and is absorbed. The safety of SprayGel has been shown in a few gynecologic and colorectal studies [68-71].Although early preliminary clinical trials showed its effectiveness, a larger-scale study was stopped owing to a lack of efficacy.
Future advances
In the absence of any clinically proven means of preventing adhesions from forming, the onus lies with the surgeon to try and minimalise their occurrence by improved and assiduous surgical techniques. The advent of laparoscopic surgery may alter the incidence of adhesions and adhesive obstruction after abdominal surgery. The reduced bowel trauma from handling, the absence of large abdominal wounds and the exclusion of foreign material such as lint, gauze and starch from the abdominal cavity must reduce adhesion formation after laparoscopic surgery. One study has already demonstrated that when a stimulus is applied at open laparotomy in an animal it produces more adhesions than when the same stimulus is applied through the laparoscope [72]. No additional adhesions were found at remote areas when the laparoscope had been used. Despite the promise of laparoscopic surgery, adhesions will continue to be a major source of concern for surgeons, not only because of the technical difficulties they present but also because of the volume of work they generate. It is possible that in the future these problems may be reduced by some form of rt-PA peritoneal lavage after surgery or adhesion division that will deter adhesion formation or re-formation and this will go some way in lightening the burden of a pathological process produced by surgery itself.
Conclusion
Postoperative adhesions are a significant health problem with major implications on quality of life and health care expenses. General intraoperative preventative techniques, such as starch-free gloves, avoiding unnecessary peritoneal dissection, avoiding spillage of intestinal contents or gallstones, and reducing remaining surgical material, may reduce the risk of adhesions and should be applied in every patient. Laparoscopic techniques are preferable to open techniques whenever possible. In high-risk procedures the use of bioabsorbable mechanical barriers should be considered.
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