Abstract
Enzymes are complex macromolecules of amino acids which biocatalyse various body processes. The aim of this study is to evaluate the effect of oral enzymes for control of infection and inflammation in post operative septoplasty cases. 40 patients planned for septoplasty under general anaesthesia were taken up for study. 20 patients were included in group E and were given a combination of oral enzymes postoperatively. Remaining 20 patients were included in group D and were given diclofenac and paracetamol combination postoperatively. Patients were evaluated post operatively after 1, 2 and 4 weeks for post operative pain , swelling , congestion , patient satisfaction and other criterias. The results showed that pain and swelling was significantly less in oral enzymes group . There was less nasal obstruction , discharge and more patient satisfaction in enzyme group. There were less complications in enzyme group. So it can be concluded that oral enzymes are more effective for control of infection and inflammation in post operative septoplasty cases.
Keywords: Septoplasty, Bromelain, Trypsin, Rutoside, Post operative pain, Inflammation
Introduction
Nasal obstruction is the most common problem that brings the patient to ENT OPD and septal deviation is the frequent structural etiology. Surgical correction of the septum is one of the most common ENT procedure. Septoplasty causes mild to moderate facial pain in the post operative period. It can lead to mucosal swelling, crusting and nasal discharge in the post operative period which can last from few days to several weeks.
NSAID’s (Non Steroidal Anti Inflammatory Drugs) and Paracetamol are commonly used post operatively [1]. But paracetamol causes inadequate relief. On the other hand, side effects of NSAID’s and opioids decrease patient satisfaction [2]. They cause bleeding, gastro intestinal irritation, nausea and vomiting [3].
Enzymes are complex macromolecules of amino acids which biocatalyse various body processes. For pharmaceutical uses they are harnessed from plants, fungi, bacteria and animals [4]. Some past studies have shown their role in acute sinusitis for reducing sinus pain and throat pain [5]. Very few studies are available regarding their role in inflammation [6]. Inspite of their potential, they have remained largely underestimated and unexploited. Various enzymes combination for infection and anti-inflammation exist in market containing bromelain, trypsin and rutoside. This study on oral systemic enzymes aims to highlight the role and safety of oral enzymes in post operative septoplasty cases for control of infection and inflammation.
Materials and Methods
This study was conducted in Department of ENT, MMMC & H from May 2013 to April 2014. 40 patients scheduled for septoplasty under general anaesthesia, aged between 18 to 60 years were enrolled in the study after obtaining written consent from the patients. The approval of local ethics committee was taken. Exclusion criteria were pregnant or nursing mothers, haemophiliacs, severe liver damage and those on blood thinning drugs like aspirin, warfarin, acute infection or allergy. All the patients were operated by the same surgeon and the anaesthesia was given by the same anaesthetist performing this study.
The patients were randomized alternatively into study group and control group. 20 patients taken in study group were given one commercially available combination of enzymes post operatively containing bromelain, trypsin and rutoside (enzoheal, rutoheal, zymogesic) three times a day, 30 min before or 2 h after meals (Group E). Remaining 20 patients in control group were given diclofenac and paracetamol post operatively(Group D). The above treatments were given for 2 weeks post operatively. All the patients in both groups were put on same antibiotic and anti-histaminic decongestant.
The patients were assessed post operatively at the end of 1, 2 and 4 weeks. The assessment points were:
The patient satisfaction was assessed according to LIKERT SCALE as 1—completely comfortable, 2—very comfortable, 3—slightly comfortable, 4—painful, 5—very painful at each visit.
The patients were assessed for burning sensation, bleeding from nose, nasal blockage, headache, nasal discharge, sneezing at each visit.
The nasal cavities were examined using nasal endoscope at each visit for oedema, discharge, crusting, scars, adhesions.
The patients were enquired about any systemic side effect or complication on taking the drug.
Results
Forty patients who gave consent were enrolled in this study. All the cases were performed under general anaesthesia. Data was collected on all patients. All the patients were in the age group of 18–60 years. The majority of patients were in the younger (60 %) and middle age group. Only 2 patients were above the age of 50 years (Table 1). Male and Female patients were almost equal (Table 1).
Table 1.
Age and sex wise distribution
| Age group | Male | Female | Total |
|---|---|---|---|
| 18–30 | 12 | 12 | 24 |
| 31–50 | 8 | 6 | 14 |
| 51–60 | 1 | 1 | 2 |
| Total | 21 | 19 | 40 |
20 patients were randomized to use one commercially available combination of enzymes post operatively containing bromelain, trypsin and rutoside (enzoheal, rutoheal, zymogesic) three times a day for 2 weeks. Remaining 20 patients in control group were given NSAID’s (diclofenac and paracetamol) post operatively for 2 weeks. The patients were assessed post operatively at the end of 1, 2 and 4 weeks.
Patient satisfaction was higher in group E using oral enzyme combination at the end of 1 and 2 weeks than group D using NSAID’s. It was almost same at the end of 4 weeks.
Post operative pain was observed in 3, 2 and nil patient of group E at the end of 1, 2 and 4 weeks respectively, whereas in group D post operative pain was observed in 8, 6 and 1 patient at the end of 1, 2 and 4 weeks respectively (Table 2).
Table 2.
Post operative symptoms in both groups
| Group | 1 week post op. | 2 weeks post op. | 4 weeks post op. | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Pain | Nasal blockage | Nasal discharge | Pain | Nasal blockage | Nasal discharge | Pain | Nasal blockage | Nasal discharge | |
| E (oral enzymes) Total patients—20 | 3 | 2 | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| D (NSAID) Total patients—20 | 8 | 6 | 5 | 6 | 4 | 3 | 1 | 3 | 2 |
Nasal blockage was present in 2, 1 and nil patient in group E at the end of 1, 2 and 4 weeks respectively, while in group D it was evident in 6, 4 and 3 patients respectively. This shows that nasal obstruction is much less when oral enzymes are used post operatively (Table 2).
None of the patients in group E had nasal discharge while 5, 3 and 2 patients in group D had purulent discharge at the end of 1, 2 and 4 weeks respectively though both the groups were given same antibiotics and anti histaminic. This shows the role of oral enzymes in preventing post operative infection (Table 2).
None of the patients in both groups had any bleeding from nose or sneezing.
On post operative nasal endoscopic examination, nasal cavity was examined for degree of discharge, oedema, crusts, scar and adhesion formation (Table 3).
Table 3.
Post operative nasal endoscopy findings in both groups
| Group | 1 week post op. | 2 weeks post op. | 4 weeks post op. | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Nasal oedema | Non healed scar | Nasal discharge | Nasal oedema | Non healed scar | Nasal discharge | Nasal oedema | Non healed scar | Nasal discharge | |
| E (oral enzymes) Total patients—20 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| D (NSAID) Total patients—20 | 8 | 2 | 5 | 5 | 1 | 3 | 2 | 0 | 2 |
For oedema, in Group E at end of 1st post operative week, only 3 patients had oedema out of which only 1 was severe. While at the end of 2nd and 4th post op (post operative) week none of the patients had oedema. Where as in group D 8 patients had oedema at the end of 1st week out of which three had severe oedema while at the end of 2nd and 4th weeks 5 and 2 patients respectively had oedema.
Regarding discharge, in Group E none of the patient had discharge post operatively, while 5, 3 and 2 patients in group D had purulent discharge at the end of 1, 2 and 4 weeks respectively though both the groups were given same antibiotics and anti histaminic. This shows the role of oral enzymes in preventing post op infection (Table 2).
None of the patients in group E had crusting, adhesion or scar formation post operatively. Whereas 2 and 1 patient had non healed scar in group D at the end of 1 and 2 weeks respectively. This proves role of oral enzymes in wound healing.
None of the patients in both groups had incidences of septal perforations or synechiae formation post operatively.
Regarding the drug related side effects, in group E 2 patients developed diarrhea at 2 weeks post op. No other patient had any other side effect.
Whereas in group D, 3 patients had nausea and vomiting at 1 week post op and 2 patients had the same at 2 weeks post op. 2 patients of group D had diarrhea at 1 week post op and 1 patient had the same at 2 weeks post op. 3 patients of group D also had gastro intestinal upset at 1 week post op and 2 at 2 weeks post op. The complaint of abdominal pain was also noted in group D patients.
After noticing the side effect the drug on those patients was stopped immediately in both groups.
No side effect was noted after stoppage of drugs at 4 weeks post op.
No other serious side effect was noted in either of the groups.
These results show less incidence of side effects with oral enzymes as compared to NSAID (Table 4).
Table 4.
Drug related side effects in both groups
| Diarrhoea | Nausea and vomiting | Gastro intestinal upset | ||||
|---|---|---|---|---|---|---|
| E (oral enzymes) Total patients—20 | D (NSAID) Total patients—20 | E (oral enzymes) Total patients—20 | D (NSAID) Total patients—20 | E (oral enzymes) Total patients—20 | D (NSAID) Total patients—20 | |
| 1 week post op. | 0 | 2 | 0 | 3 | 0 | 3 |
| 2 week post op. | 2 | 1 | 0 | 2 | 0 | 2 |
| Total | 2 | 3 | 0 | 5 | 0 | 5 |
The bold signifies the total number of patients with side effects in both groups
Discussion
The efficacy of oral enzymes as compared to NSAID’ in post operative septoplasty cases was investigated in this study. The primary aim of this study was to evaluate the role of oral enzymes in controlling inflammation and infection and the patient satisfaction and the second aim was to study the adverse affects of the drugs, if any.
We have used a combination of oral enzymes commercially available containing bromelain, trypsin and rutoside each containing bromelain 48 mg, trypsin 90 mg and rutoside 100 mg. Our surgery included only septoplasty cases to have uniformity with regards to nasal inflammation in order to remove any bias.
Septoplasty is one of the most common surgeries practiced by ENT surgeons today. It causes mild to moderate facial pain in the post operative period. It also leads to mucosal swelling which can last up to several weeks. Several incidences of post operative infection have also been reported in literature. NSAID’s and Paracetamol are commonly used post operatively [1]. Paracetamol provides inadequate postoperative analgesia. Side effects of NSAID’s and opioids decrease patient satisfaction. [2] Bleeding, gastro intestinal irritation, nausea and vomiting are the common side effects of them in the literature. NSAID’s allergy can cause facial swelling, wheezing, skin rash. There is risk of gastro intestinal bleed with NSAID’s. Long term use of NSAID’s can lead to gastric ulcer and even increase risk of heart disease or stroke.
In our study also the patients on NSAID’s had greater side effects than the other group. The side effects observed were nausea and vomiting (25 %), gastro intestinal upset (25 %) and diarrhoea (15 %). Patients recovered from these effects on stoppage of drugs. Though no other major side effects of NSAID’s was noted, but the reason could be our short duration of usage of these drugs (2 weeks). Whereas in patients on oral enzymes no side effect was noted in first post op week, only in the second post operative week two patients (10 %) had diarrhoea. These results shows safety of oral enzymes as compared to NSAID’s. Even the literature available supports the same. In a study conducted. it has been noted that no undesirable adverse effect with oral enzymes, only mild diarrhoea with overdose [7]. Studies demonstrate no teratogenic effect of oral enzyme mixtures. Another study showed minimal harmless change in colour, consistency and odour of stool with enzyme mixture. These results correlate with our study and proves that oral enzymes are much safer than NSAID’s as related to their adverse effects on human body.
These oral enzymes are harnessed from plants, fungi, bacteria and animals for pharmaceutical use [4]. Bromelain is harnessed from pineapple stems (Ananas Comosus). Pineapple has been used as a medicinal plant by folks of several tropical native cultures and its enzyme bromelain has been chemically known since 1876 [8]. Rutin and Trypsin are harnessed from staphylococcus aureus.
Systemic enzyme therapy overcomes the cytokine storm or immunosuppression seen in post operative infections and to salvage the host immune system and hence aid in control and elimination of infection. Bromelain increases proliferation of mononuclear cells, proliferation of IL-6, GM-CSF,TNF-alpha and IFN- gamma production [9]. These enzymes modulate arachidonate pathway in such a way that thromboxane production is decreased with no effect on cyclooxygenase. This leads to decrease in oedema and inflammation [10]. Enzymes such as rutin are strong antioxidants and effectively combat the harmful free radicals such as nitric oxide released during inflammatory process [11]. These enzymes block proinflammatory metabolites that propagate the inflammation [12].
Inspite of their potential, oral enzymes have remained largely underestimated and unexploited. Fewer studies are available in nature. In a study involving 193 patients, serratiopeptidase acted rapidly to reduce inflammation [6]. Bromelain role has been studied in acute sinusitis. It reduces sinus pain and throat pain [13]. Experimental runs of enzymes as wound debridement agents have given positive results. Bromelain and other enzymes have been extensively investigated for use in wound bed preparation [14]. Various studies have shown role of these enzymes in decreasing inflammation after surgery or trauma. In various literature available, oral enzymes reduce average number of days for reduction of pain from 3.5 to 1.5 and average number of days for disappearance of inflammation from 6.9 to 2.0. Similarly also in our study we have observed a significant decrease in post operative pain on using oral enzymes. We have also got a significant lower incidence of nasal oedema and nasal blockage when oral enzymes are given post operatively as compared to NSAID’s. This shows the positive results of oral enzymes in reducing pain and inflammation. We have also observed better and early healing of the post operative scar when oral enzymes are used post operatively. This signifies their role as wound healing agents.
Papain has also been found to enhance the chemotherapeutic efficacy of antibiotics in mice with septicaemia [15]. Ishikawa et al. has also shown that bromelain has a protective effect when used with antibiotics in experimental infections in mice caused by various bacteria [16]. In our study we observed no incidence of purulent nasal discharge on using oral enzymes even endoscopically as compared to NSAID group (25 %) even though same antibiotic was used in both group. This clearly shows that oral enzymes do have a role in control of post operative infection. The fact that they themselves have a antiseptic role or they enhance the antiseptic potential of the antibiotic needs to be further investigated.
Conclusion
Oral enzymes are highly effective in controlling post operative inflammation and infection as compared to other available drugs like NSAID’s. Patient satisfaction is much higher when oral enzymes are given post operatively. The symptoms of post operative pain, nasal obstruction and nasal discharge are much less on using oral enzymes. There is also less incidence of nasal oedema and better healing of post operative scar on using oral enzymes. They also cause much lesser side effects and are much safer as compared to NSAID’s.
So we can conclude that use of oral enzymes in post operative cases probably would benefit our patients. There is scope of future trials along this line of management.
Acknowledgments
We would like to thank our institute Maharishi Markandeshwar Medical College and Hospital for its support and the patients for cooperating with the study protocol.
Conflict of interest
The authors declare that there is no conflict of interest.
Contributor Information
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