Comparative evaluation of analgesic and anti-inflammatory efficacy of ibuprofen and traumeel after periodontal flap surgery: A randomized triple-blind clinical trial.

BACKGROUND: Pain management after performing flap surgery is of paramount importance. Taking into consideration the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), and the advantages of homeopathic medication, the analgesic and anti-inflammatory properties of ibuprofen (NSAID) and traumeel (homeopathic AID) following flap surgery were evaluated.
MATERIALS AND METHODS: A randomized, triple-blinded, split-mouth clinical trial, with a sample size of 20 (age range of 20-60 years) was planned. Subjects included patients diagnosed with moderate chronic generalized periodontitis. Two quadrants for each subject were operated on, with an interval of 3 weeks. Random assignment of the operated quadrants to the following medication protocols was carried out by a third person: Ibuprofen, 600 mg and traumeel, 600 mg (up to three tablets) every 8 h for first 24 h and SOS (Si Opus Sit/if needed) thereafter for a period of 1 week as pain medication, respectively. After 1 week, sutures were removed. Primary outcomes were mean postoperative pain (modified visual analog scale) and number of tablets consumed in 1 week. The secondary outcome was postoperative tissue response. Any adverse effects were recorded.
RESULTS: Number of tablets consumed and pain perception was lower in traumeel compared to ibuprofen Group (P < 0.001). A better tissue response was shown by the group treated with traumeel as compared to the ibuprofen receiving group (P < 0.05). Three patients reported adverse drug reactions after consumption of ibuprofen.
CONCLUSION: The present study suggested that while managing pain following flap surgery, traumeel was superior as compared to ibuprofen, with minimal or no side effects. Copyright:

INTRODUCTION

Postoperative pain is common following periodontal flap surgeries and ranges from mild-to-moderately severe.[1] There is a vast array of analgesics available, and periodontists are often challenged while choosing the safest and most effective analgesic to manage pain after the surgical procedure.

Ibuprofen has been considered as a safe and inexpensive choice of analgesic.[2] However, it is associated with some serious side effects.[1]

A homeopathic complex remedy, traumeel, which has natural ingredients, and is used for treating inflammation, trauma, and degenerative processes.[3] Traumeel has also demonstrated anti-inflammatory and analgesic effects in both trials of a clinical nature as well as in vivo experiments involving models, such as maxillofacial inflammations, periodontitis, and pain syndrome after dental canal filling.[34] Patient acceptance is also very high.[5]

The rule of thumb for analgesic therapy is to use the lowest dose with minimum side effects to achieve the desired effect. The present study compared the efficacy of ibuprofen and traumeel in terms of analgesia and anti-inflammatory actions following flap surgery in terms of pain and tissue response (tissue edema [TE] and color).

MATERIALS AND METHODS

Source of data

The study subjects were selected from patients reporting to the outpatient Department of Periodontology and Oral Implantology, to take part in this prospective, randomized, triple-blind split-mouth clinical trial.

Method of collection of data

A sample comprised 20 patients, 20–60 years of age having moderate chronic generalized periodontitis (AAP 1999) without any other medical and smoking or drinking history, requiring periodontal flap surgery in contralateral quadrants were included in the study. Pregnant ladies, lactating mothers, patients on medications (e.g., analgesics or corticosteroids) during the period of the study and patients suffering from peptic ulceration were not included.

Informed consents from the study subjects were obtained in the written form after explaining the protocols of the study. Ethical clearance was obtained from the Ethical Committee.

Clinical procedure

The probing pocket depth and clinical attachment level from six sites on each tooth were recorded to determine the periodontal status. Orthopantomograph was taken to assess the extent of bone loss.

The same clinician performed all surgeries (Modified Widman flap surgery). The anesthetic technique was standardized for the study. To obtain surgical anesthesia, 2% lignocaine in the required amount was used along with 1:10,000 epinephrine. For reliable results, it was essential to ensure that the contralateral sides of the patients receive as much identical procedures as possible, along with the similar duration of surgeries. A full-thickness mucoperiosteal flap was reflected, followed by thorough degranulation, scaling and root planning, and osseous recontouring if required. Approximation of the mucoperiosteal flaps was done with interrupted direct loop sutures using 4-0 black silk suture. Coe-pak was mixed and applied. Patients were given verbal and written postoperative instructions.

A third person dispensed either ibuprofen, 600 mg or traumeel (Heel GmbH, Baden-Baden, Germany) 600 mg (up to three tablets) every 8 h for first 24 h and (Si Opus Sit/if needed) thereafter for 1 week as pain medication as per a log that maintained randomization. The study was triple-blinded, with the patient, primary investigator and the statistician blinded until the completion of the study.

A customized chart was provided to the subject, to self-report pain following the surgical procedure. A visual analog scale (VAS) was used to measure pain daily at night for 7 days [Table 1][678] and to record the number of tablets consumed for each day for 7 days. These outcomes were considered as primary.

Table 1

Modified visual analog scale

0–2 – No pain; 2.1–4 – A little pain; 4.1–6 – Considerable pain; 6.1–8 – Lots of pain; 8.1–10 – Worse/maximum pain

The patients were recalled 1 week postoperatively for suture removal. On the same day, tissue response, i.e., TE and tissue color (TC) was assessed in both buccal and lingual/palatal surfaces of each tooth [Table 2].[7]

Table 2

Tissue response (tissue edema and tissue color) – Based on Sanz-Moliner JD et al., 2013 visual analysis

Tissue Edema of the gingiva	Tissue Color of the gingiva
1=Absent	1=Pink
2=Slight	2=Mixed
3=Moderate	3=Red
4=Severe

Any adverse effects (e.g., nausea, vomiting, gastric discomfort, gastric acidity or burning sensation, dizziness, dyspepsia, pruritus, diarrhea, etc.) experienced by patients were noted in the proforma.

After 3 weeks of the first surgery, patients were recalled for the second surgery. The same surgical procedure was followed on the contralateral side. Drugs were changed according to the randomization log.

Statistical analysis and methods

A structured pro forma was used to collect data and entered into MS excel sheet. The analysis was performed using the SPSS software version 23.0 IBM USA (IBM SPSS Statistics for Windows, Version 23.0. Bangalore, Karnataka, India). Qualitative data were expressed in percentage and frequency. Quantitative data were expressed in terms of mean and standard deviation (SD). Comparison of mean and SD between the two groups was made using the Student's paired t-test to assess if the mean difference between groups is significant or not. To determine the significance of the study parameters measured on a categorical scale, Chi-square analysis was performed. Quantitative data results were presented as mean ± SD, whereas categorical data results were presented as number (%). Statistically significant results were denoted by a value of P < 0.05, while the results were considered highly significant when value of P < 0.001 was obtained.

RESULTS

After the computation of results, the third person disclosed the names of drugs. Compliance with medications was 100% and study guidelines were followed by all the patients.

The present study included a total of 20 patients (females = 3 and males = 17) with age group ranges of 20–60 years (38.40 ± 8.12) having moderate chronic generalized periodontitis [Table 3].

Table 3

Descriptive statistics of the variables

	n	Mean	Standard deviation	Standard error	Range	Minimum	Maximum
Age	20	38.40	8.12	1.82	31	25	56
CAL (mm)	20	3.65	0.29	0.06	0.9	3.1	4.0
% of sites with CAL of 3-4 mm (%)	20	88.21	11.73	2.62	39.0	61.0	100.0

N – Total number of patients; CAL – Clinical attachment loss; mm – Milli meter

Statistically highly significant (P < 0.001) reduction of pain was observed in traumeel compared to ibuprofen. Consumption of traumeel was statistically low as compared to ibuprofen (P < 0.001) [Table 4].

Table 4

Comparison of mean modified visual analog scale in a period of 1 week between ibuprofen and traumeel

Analgesic	n	Mean	Standard deviation	t	df	P	Inference
Ibuprofen	20	1.19	0.43	8.71	19	0.0001 (<0.001)	Highly significant
Traumeel	20	0.31	0.14

P<0.05 was considered as statistically significant whereas a P < 0.001 was considered as highly significant. N – Total number of patients; t – Student’s paired t-test; df – Degree of freedom; P – Probability

There was a significant difference (P < 0.05) in tissue response in terms of reduced TE [Table 5] and normalization of color Table 6 in traumeel group compared to ibuprofen.

Table 5

Comparison of number of analgesics consumed in a period of 1 week between ibuprofen and traumeel

Analgesic	n	Mean	Standard deviation	t	df	P	Inference
Ibuprofen	20	7.45	2.98	4.29	19	0.0001 (<0.001)	Highly significant
Traumeel	20	4.00	1.41

P<0.05 was considered as statistically significant whereas a P<0.001 was considered as highly significant. N – Total number of patients; t – Student’s paired t-test; df – Degree of freedom; P – Probability

Table 6

Comparison of mean tissue edema between ibupfen and traumeel

Analgesic	n	Mean	Standard deviation	t	df	P	Inference
Ibuprofen	20	1.09	0.12	2.52	19	0.02 (<0.05)	Significant
Traumeel	20	1.02	0.05

P<0.05 was considered as statistically significant whereas a P<0.001 was considered as highly significant. N – Total number of patients; t – Student’s paired t-test; df – Degree of freedom; P – Probability

Of 20 patients, 3 (15%; females = 2 and male = 1) reported adverse drug reactions after consumption of ibuprofen, compared to none with traumeel.

DISCUSSION

The present study was conducted to compare the analgesic and anti-inflammatory effects of ibuprofen and traumeel after flap surgery along with any adverse effects associated with each one of them.

In this randomized triple-blind split-mouth clinical trial, a pain model using “periodontal flap surgery” was adopted as it is most frequently used in periodontal practice. Due to pain subjectivity, a split-mouth study seems to be ideal for this kind of clinical trial once the patient serves as his own control. The triple-blind design and randomization increased the sensitivity of the present study results. Equality of only moderate chronic generalized periodontitis grouping in the present study has the advantages of availability of patients (most of the population are affected with moderate chronic generalized periodontitis (CGP)) and making direct comparisons between such groups more valuable. Three weeks gap between two surgeries is the healing period, to achieve the maximum tensile strength of the tooth-gingival flap interface following periodontal surgery.[9] Ibuprofen is time tested and effective analgesic after periodontal flap surgery based on extensive literature information[101112] and traumeel is a proven effective analgesic homeopathic complex remedy.[5131415] Hence, no analgesic control/placebo was used in the present study. Postoperative pain generally lasts for 24 h, with greater intensity at 6–8 h[1617] which justifies prescription of tablets in 8h period on the 1st day of surgery.

A modification of the VAS was given to the patients for rating the postoperative pain for the previous 1 week [Table 1]. Unlike the VAS, this scale allows objective numeric values.[678] The present study showed statistically highly significant (P < 0.001) reduction of pain [Table 4] and consumption of less number [Table 5] of traumeel compared to ibuprofen. Ibuprofen acts by inhibiting immunoreactive prostaglandin E2 (iPGE2) production in the periodontal tissues. iPGE2 is a potent vasodilator and hyperalgesic agent having proinflammatory properties.[18] It was noted that the action of traumeel is different from that of ibuprofen. It has been noted that when an inflammatory response is triggered, traumeel shows synergism with the other components during the various inflammatory phases. This interaction may be the reason for a highly efficient anti-inflammatory effect of traumeel.[1519] Moreover, by stimulating the production of the inhibitory cytokine, the process of wound healing is accelerated by traumeel. It also transforms growth factor-beta, hence indirectly preventing pro-inflammatory lymphocytes from continuing the inflammatory reaction.[15] Trumeel regulates the automated coordination of the local inflammation process of an acute nature. It does not interact with a specific type of cell.[13] The production of superoxide anion by unstimulated and stimulated peripheral blood polymorphonuclear neutrophils of periodontitis patients may also significantly decreased by traumeel.[20] These may be the possible reasons for reduced pain perception and less tablets consumption in traumeel group compared to ibuprofen.

Traumeel is an effective analgesic in the medical field. A previous clinical trial has proved that traumeel may also be beneficial in children undergoing bone marrow transplantation, by significantly reducing both the severity and duration of stomatitis resulting from chemotherapy.[14] Traumeel was tested compared with diclofenac (another potent nonsteroidal anti-inflammatory drugs [NSAID]) in patients with epicondylitis, for effects on symptomatic relief. It was shown to have significantly superior pain relieving properties as compared to diclofenac.[3] Another trial compared traumeel with diclofenac for pain reduction and improvement of ankle mobility after acute ankle sprain. Effect on pain and ankle mobility for traumeel and diclofenac was found to be comparable and well tolerated.[15] Added advantage of traumeel is its beneficial effects on periodontal tissues. Scaling and root planing (SRP) with traumeel is effective in establishing the balance of the salivary parameters, thus improving periodontal health.[4]

The present study showed better (P < 0.05) tissue response in terms of TC [Table 6] and TE [Table 7] in the group receiving traumeel than the ibuprofen group. When tissue response inference [Table 2][7] is compared, mean values of both ibuprofen (TE and color – 1.09) and traumeel (TE and color – 1.02) showed absent to slight TE and pink to mixed TC. Periodontal flap surgery usually causes mild postoperative swelling in the first 3 days after surgery. In an animal experiment, to assess the effect of traumeel on blood-induced inflammation, rats were administered with traumeel, followed by hind-paw injection with 0.1 ml of homologous blood after 1 h. The edema developed was recorded over a period of 5 h. Saline was used to treat the control group. It was found that the edema reduced rapidly in the traumeel groups as compared to the control. This effect of traumeel was associated with a significant reduction in interleukin-6 production. According to this study, the healing process was quickened by traumeel, instead of the blockage of development of edema from the beginning,[19] leading to better tissue response in traumeel compared to ibuprofen.

Table 7

Comparison of mean tissue color between ibuprofen and traumeel

Analgesic	n	Mean	SD	t	df	P	Inference
Ibuprofen	20	1.09	0.12	2.52	19	0.02 (≤0.05)	Significant
Traumeel	20	1.02	0.05

P<0.05 was considered as statistically significant whereas a P<0.001 was considered as highly significant. N – Total number of patients; t – Student’s paired t-test; df – Degree of freedom; P – Probability

In the present study, 15% of patients reported gastric irritability after consumption of ibuprofen. Ibuprofen is a nonselective inhibitor of cyclooxygenase-1 (COX-1) and COX-2. Inhibition of COX-1 leads to the inhibition of PGI2 (prostacyclin) which has gastroprotective properties.[2122] Endoscopic studies involving the upper gastrointestinal (GI) tract concluded that of the patients who are administered NSAIDs, a 15%–30% develop stomach ulcers.[21] Traumeel group in the present study did not report any adverse drug reactions.[3131415] The action of traumeel is different than that of ibuprofen. Rather than directly inhibiting synthesis of prostaglandin, traumeel shows antioxidative and immunomodulatory properties. It also decreases the activity of phospholipase A2, consequently modulating arachidonic acid.[23] This may be credible reason for no gastric irritability in traumeel group in the present study.

The present study was a preliminary study comparing the analgesic and anti-inflammatory effects of traumeel with ibuprofen on pain associated with postoperative periodontal flap surgery and tissue response. Probable limitation of the present study may be Hawthorne effect (especially in second surgery). Long-term studies conducted a larger sample size, and using other types of periodontal surgery that are expected to cause more pain and swelling (perioplastic surgery, bone-resective, and regenerative surgeries)[17] are necessary further assess the effectiveness of analgesic, anti-inflammatory effects of traumeel.

CONCLUSION

The present study was the first study to compare the analgesic, anti-inflammatory, and tissue response to ibuprofen and traumeel after periodontal flap surgery. Extensive literature search has revealed a paucity in studies that assess the use of traumeel for pain prevention and tissue response in periodontal flap surgery; hence, comparison of the present study with other literature is limited. Traumeel presented no adverse GI effects, better tissue response, high patient compliance, and was highly effective in controlling postsurgical pain. This clearly demonstrates the effectiveness of the traumeel in controlling both pain and tissue response post periodontal flap surgery along with the added benefits in improving periodontal health.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.