Vitamin E Effect On Decreasing Post Operative Adhesion Biology Essay

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Introduction: Adhesions as abnormal scar tissue are common following gynecological operations and can cause chronic pelvic pain, infertility, poor outcomes of next surgeries, intestinal obstruction. Oxygen free radicals are known as one of the main causes of adhesion formation so vitamin E antioxidant effects have always been an interesting subject for researchers during previous years in this field.

Objective: This study is to evaluate the effect of vitamin E on decreasing post operative adhesion in rat uterine horn.

Methods & Materials: This experimental study was performed on 45 non-pregnant female rats randomized in 3 equal groups. In all groups after general anesthesia and sterile exploration, anti-mesenteric surface of left uterine horn was traumatized using a single-polar couther. The right side was traumatized by scalpel. In the 1st and 2nd groups intra-peritoneal and intra muscular vitamin E were administrated, respectively while in the control group just normal saline solution was poured on the horns. Following 4 weeks recovery, second laparotomy was performed to grade the adhesions, if any. Dose of vitamin E for each rat was 10 IU (50 u/kg).

Results: In this study, vitamin E not only had no effect on preventing adhesion formation in the right uterine horn traumatized by scalpel, but also we were surprised to see no adhesion formation in right uterine horn in the control group. However vitamin E administration in the left side (both intra-peritoneal & intra-muscular) traumatized by cautery, had significantly a preventive effect against adhesion formation. In compare with intra-peritoneal administration, intra-muscular vitamin E had greater protective effect.

Discussion & Conclusion: Considering vitamin E availability, cost-efficacy and safety in high doses it can be injected intra-muscularly before operations to prevent adhesion formation.

Key word: Adhesion, Vitamin E, uterine horns, Peritoneum, Laparotomy

Introduction:

Adhesions as abnormal scar tissue are common following gynecological operations and are seen during healing processes (1). In some cases they can lead to some complications such as: Chronic pelvic pain, infertility, poor outcomes of next surgeries, intestinal obstruction, etc.

Adhesion mechanism is known as an inflammatory continuous event during the healing process where the peritoneum is traumatized. Although this inflammation occurs normally but in abnormal situations such as ischemia, fiber bands will remain and result in adhesion formation. This fact that peritoneum surrounds all organs in pelvic -except ovaries in women- has led to high prevalence of adhesions following operations of this region (1, 2).

There are contraversies on how to prevent and decrease adhesions and no decisive method has been substantiated. These solutions can be categorized in 3 subgroups: improving surgical methods, using barriers and finally administrating pharmacological agents. The first step to have less adhesion is to use less traumatizing surgical procedures. Laparoscopic operation was a great advance to minimize post-laparotomy adhesion however; some adhesions are reported following laparoscopy, too. Other simple surgical hints could be: cleaning talcum powder of the surgical gloves before manipulating peritoneum, using absorbable sutures as few as possible, not to use rough sponges and etc.

Barriers themselves consist of absorbable, non-absorbable and liquid ones like Oxidized Regenerated Cellulose (ORC), Expanded Poly Tetra Fluoro Ethylene (EPTFE) and Crystalloids, respectively. But their efficacy was not consistent in all cases (3, 4).

Several pharmacological agents have been tried to prevent adhesion formation in different studies. Basbug and coworkers (2004) showed the preventive effect of hyaloronic acid plus heparin on adhesion formation in rat uterine horn (5).

In the year 2007 Melatonin effect on adhesion formation in the rat secum and uterine horn was assessed by Cendiz et al (6). It was documented that the use of Melatonin in prioe surgery showed a significant lower amount of adhesion formation compared to the control group. In many studies oxygen free radicals are known as one of the main causes of adhesion formation so that they may cause further tissue damage and therefore leading to more adhesion formation. (7).

Vitamin E as an antioxidant vitamin plays important roles in human health and reproductive systems while it's an essential nutrient for fetus and infants to grow appropriately (1-3). Vitamin E antioxidant effects have always been an interesting subject for researchers during previous years in this field (8-10). In two separate studies efficacy of oral, subcutaneous and intra-peritoneal vitamin E in preventing post-operative adhesion formation were compared with control groups and positive results are obtained(8,9). Due to proven side effects of other pharmacological agents such as melatonin (6,11) and sodium carboxyl methyl cellulose (10) and of course their high prices and unavailability, it seems that vitamin E can be a beneficial choice. In another study conducted in 2004 on rats, intra-peritoneal injection of vitamin E was significantly more efficient in preventing adhesion formation in compare with intra-muscular administration (8).The purpose of this study is to evaluate the effect of vitamin E on decreasing post operative adhesion in rat uterine horn. The effect of different administration ways when rat's peritoneum is traumatized in different ways is also discussed.

Method & Materials:

This experimental study was performed on 45 non-pregnant female rats with the mean weight of 200 grams. They were randomized in 3 groups, each consists of 15 rats. Vitamin E was used in the form of 100 IU/ml ampoules. Administrated dosage for each rat was 10 IU equal to 0.1cc (50 U/kg). All the surgical procedures were performed by researchers. Chloroform and then halothane and oxygen mixture were used for general anesthesia before operation. Soon after anesthesia and right before incision, their abdomens were shaved and prepped. An Inferior-middle incision with the length of 3 cm was made using the sterile technique. Skin, muscle fascia and peritoneum were exposed and uterine horns were explored.

After this exploration, in all 3 groups, a 2cm incision was made on the wide ligament of left uterine horn and it was devascularized. Then 5 points of anti-mesenteric surface of left uterine horn were traumatized using single-polar couther with the power of 1 voltage. On the surface of the other horn (the right one) and also on the peritoneal wall of that side 5 scratches were made by scalpel. In this group 0.1 cc (10 IU) intra-peritoneal vitamin E was injected while in the second group the same dosage was administrated intramuscularly before making any incisions. In control group normal saline solution was poured on uterine horns. In all groups monofilament surgical sutures were used to close incisions in two layers. Post-operation conditions were the same for all cases. Following 4 weeks recovery, second laparotomy was performed to grade adhesion formation.

In this study adhesion was defined as joining bands from the traumatized points to intestines, fascia and omentum.

Vitamin E was purchased from Zahravi Corporation in Tabriz.

Adhesion formation was measured in terms of severity and extent according to scales shown in table1 and 2, respectively. For each horn two grades were added to calculate the final score ranging from 0 to 4. In the other word 30 scores were achieved for each group and the mean values were calculated. One-way ANOVA method was used to analyze data with SPSS software, version 12.The P-value<0.05 was considered as statistically significant.

Adhesion Extent

Grade

No adhesion

0

Adhesion in 25% of traumatized points

1

Adhesion in 50% of traumatized points

2

Adhesion in all of the traumatized points

3

Table-1: Adhesion Extent Scale

Adhesion Severity

Grade

Not resistant against resection

0

Moderate resistant against resection

0.5

Resection just by sharp dissection

1

Table-2: Adhesion Severity Scale

Results:

As shown in table-3 vitamin E not only had no effect on preventing adhesion formation in the right uterine horn but also we were surprised to see non-significant adhesion formation in the intramascular case group [P-value=0.15] but not in the intraperitoneal group [P-Value=0.35] . Surprisingly, no significant adhesion was formed in right uterine horn in the control group members(P-value=0.34).

Groups

Group1

(control group)

Group2

(intra-muscular vitamin E)

p-value=0.15

Group3

(intra-peritoneal vitaminE)

p-value=0.35

Adhesion Grade

Number

%

Number

%

Number

%

0

13

(87)

11

(67)

15

(100)

1

2

(13)

4

(33)

0

(0)

2,3,4

0

(0)

0

(0)

0

(0)

Table-3: Comparison the grade of right uterine horn adhesion formation among the studied groups- The difference in adhesion formation compared to control group was not significant with P-value= 0.15 in group 2, and P-value= 0.35 in group 3.

However vitamin E administration in the left uterine horn, damaged with cautery (both intra-peritoneal & intra-muscular) had significantly a preventive effect against adhesion formation. In groups 3 and 2 respectively in just 4 cases (33%, P-value=0.001) and 3 ones (20%, P-value=0.001), grade one of adhesion was detected while for control group this grade of adhesion was observed in 12 members (80%, P-value=0.028)).table-4). The difference in the case and control groups was statistically significant. (P-Value=0.01)

Groups

Group1

(control group)

Group2

(intra-muscular vitamin E)

P-value=0.001

Group3

(intra-peritoneal vitamin E)

P-value=0.001

Adhesion Grade

Number

%

Number

%

Number

%

0

3

(20)

12

(80)

11

(67)

1

12

(80)

3

(20)

4

(33)

2,3,4

0

(0)

0

(0)

0

(0)

Table-4: Comparison the grade of left uterine horn adhesion formation among the studied groups - The difference in adhesion formation compared to control group was significant with P-value= 0.001 in group 2, and P-value= 0.001 in group 3.

Overall, administrating vitamin E had a significant effect in decreasing adhesion formation or at least its grade. In compare with intra-peritoneal administration, intra-muscular vitamin E had greater protective effect.

All rats were alive after the operation. No antibiotics were administered.

Discussion & Conclusion:

Adhesion as an abnormal tissue is formed during healing process and bonds areas that shouldn't be connected. Such a response can occur following surgery, infection, trauma or radiation.

Peritoneal involving operations including gynecology ones may lead to adhesion formation (1). On the other hand, adhesions by themselves can cause pain and other complications like bowel obstruction, infertility, etc (1,2). In a well done surgery procedure with less unnecessary traumatized tissues and foreign bodies -such as sutures- these reactions can be highly prevented.

To prevent adhesions, it is assumed that surgeons understand and adhere to the principles of good surgical technique at the time of the primary surgery. Sometimes termed "microsurgical principles," these recommendations include:

Use of atraumatic instruments; Use of fine and inert suture materials; Careful tissue handling; Prevention of desiccation; Meticulous hemostasis. (12)

Surgical approach is an important factor with laparoscopy being associated with less adhesion formation compared to laparotomy. (13)

In Different studies various chemicals have been used during surgery to prevent adhesion formation which among them Dextrin and Sodium carboxyl methyl cellulose had better effects (10).

Vitamin E has antioxidant, anti-inflammatory, and antifibroblastic effects. In addition, it decreases collagen formation. In theory, it may decrease adhesion formation

In a similar study on rats (2004) intra-peritoneal vitamin E administration during surgery had a significant preventive effect on adhesion formation (8). In Hemadeh et al study (1993,) the difference in how vitamin E is used in rats (oral, subcutaneous or intra-peritoneal) was significant in favor of oral consumption (P<0.04) (9).

In our study vitamin E protective effect on adhesion was more significant when it was administrated intra-muscularly. In the other word, with intra-muscular vitamin E no adhesion was formed in approximately %33 of cases while all control ones showed various grades of adhesion. The difference was not statistically significant for intra-peritoneal administration.

Intra-muscular vitamin E had also greater effect in preventing adhesion formation of left uterine horn (traumatized with cautery) in compare with intra-peritoneal and control groups (%20 vs. %33 & %80 adhesion formation, respectively). In the right uterine horn (traumatized with scalpel) neither intra-muscular nor intra-peritoneal vitamin E decreased adhesion. Surprisingly no adhesion was observed in the control group.

The cause of stronger effect of vitamin E when administered intramuscularly compared to intraperitoneal way, might be due to the fact that inflammatory processes start in the primary hours of operation that high levels of vitamin E at this time can stop these reactions. While, in the intraperitoneal form, vitamin E is absorbed lately so that its ideal level to prevent the inflammatory processes is not achieved. The same mechanism may prevent fibroblast aggregation in the site of ulcer, scar tissue formation and adhesion. (11)

It seems that damaged tissue due to trauma forms free radicals which have critical role in adhesion formation. Also, because cauterization causes more damage than surgical scalpel, probably cauterization leads to more adhesion formation (14).

As we know, cauterization damages tissues much more in compare with surgical blade. So adhesions would occur more frequently and severely and maybe that's why we were not able to show the efficacy of Vitamin E in the scalpel group with lower level of injury.

In our study intra-muscular administration of vitamin E was the most effective way to reduce adhesions. So, it might be concluded that the role of vitamin E on decreasing postop adhesion could be different according to the intensity of damage and mode of administration, which calls for further studies.

Today, we are still far from finding the ideal adhesion-preventing agent. There is still no adhesion-preventing substance, material, or barrier that is unequivocally effective. One can reduce the adhesion formation, but not prevent it entirely. In conclusion, Considering vitamin E availability, cost-efficacy and safety in high doses it can be injected intra-muscularly before operations to prevent adhesion formation. Although our study was performed on rats, but due to vitamin E safety such a study can be conducted on higher populations of humans with longer follow-up durations to conclude definitely.

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