Journal of College of Medical Sciences-Nepal, 2010, VComparative study of tramadol and ketorolac in the pain management of third molar tooth extraction M.M. Shaik1, J. Kumar2, S. Mobina3, N. Satyanarayana4, P. Sunitha51Lecturer in pharmacology, 2Assistant Professor in Pharmacology, 4Lecturer in Anatomy, 5Lecturer in Physiology, College ofMedical Sciences, Bharatpur, Nepal3Junior Resident, St Joseph’s Dental College, Eluru, Andhra Pradesh, IndiaAbstract Objective: Clinical comparison of efficacy, duration of action, onset of action, side effects of two most commonly used analgesics tramadol and ketorolac after the third molar tooth extraction. Materials and methods: The present study was carried out at department of oral surgery, Mamata Dental Hospital, Khammam, India. 150 patients were randomly selected and divided into two groups. Group A received 50 mg of tramadol orally and Group B received 10 mg of ketorolac orally. In both groups dose was repeated for next 24 hrs. Visual scale analog was used for the collection of pain intensity from the patients. Results: In Group A, the analgesia started within 1hour and at the end of 24 hours, pain intensity was 2.12 out of 10 on visual analog scale. In Group B, analgesia started within 30 mins and at the end of 24 hours, the pain intensity was 2.98 on visual analog scale. Sedation associated with dizziness and muscle relaxation was observed with tramadol in 5% of patients and sweating in 8% patients. While in case of ketorolac, 33% of patients suffered with side effects. Among them 33% patients suffered with bleeding at the site of tooth extraction and 20% patients suffered with epigastric pain. The analgesic effect of 50 mg tramadol lasted up to 6 hours and that of ketorolac lasted for 5 hour. Conclusion: The study shows that tramadol is a suitable and safe analgesic for the relief of post-extraction pain and is more effective than ketorolac with prolonged analgesia and minimal side effects. Key Words:Tramadol, ketorolac, third molar tooth extraction, Introduction
in the mouth to accommodate the erupting wisdom
The wisdom tooth (or third molar) is usually the
teeth and therefore, they might not always come into
last tooth to erupt into the mouth anytime after about
the mouth normally. Wisdom teeth are usually either
16 years of age. Frequently, there is not enough room
impacted forwards into the tooth in front or backwards
Correspondences: Munvar Miya Shaik
into the jaw bone. An impacted wisdom tooth causes
infection in the gum surrounding the tooth leading to
Journal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1
pain and swelling. Sometimes cysts also formed due
Ketorolac is the inhibition of prostaglandin synthesis
to impacted wisdom tooth. To avoid these problems it
by competitive blocking of the enzyme cyclooxygenase
is always better to remove the tooth. however, the
management of pain consequent to tooth extraction is
The present study was conducted keeping in view
always a major concern for the individual.1, 2
giving the quicker, prolonged and safer post-extraction
The way pain is experienced is a reflection of the
analgesic after third molar tooth extraction for quicker
individual’s emotional, motivational, cognitive, social,
recovery of the patient from the post-extraction pain.
and cultural circumstances. The pain of tooth extraction
This study was the clinical comparison of efficacy, safety
is likely to be the most severe pain that an individual
and patient satisfaction of clinically widely used
experiences during his or her life.3 Many individuals
analgesics, tramadol and ketorolac. There were some
rate the pain of tooth extraction as very severe or
reports published the comparing the parenteral
intolerable. The pain of tooth extraction varies among
tramadol and ketorolac in maxiofacilary surgery.8,9
individuals, and each extraction of an individual maybe quite different. Management of post-extraction pain
Materials and methods
relieves suffering and leads to earlier mobilization,
One hundread and fifty patients from routine
shortened hospital stay, reduced hospital costs and
admissions with tooth extraction were selected
randomly during the period of 10 months from July
Tramadol is an atypical centrally-acting analgesic
2008 to April 2009 in the department of oral surgery,
because of its combined effects as an opioid agonist
Mamata Dental Hospital affiliated to Mamata Dental
and a serotonin and noradrenaline reuptake inhibitor.
College, Khammam, India. The inclusion criteria were:
The risk of respiratory depression is significantly lower
age in between 18 to 60, undergoing into third molar
at equianalgesic doses and does not depress the
tooth extraction, alertness and stability. The exclusion
hypoxic ventilatory response. It has limited effects on
criteria were: history of drug or substance abuse, allergy
gastrointestinal motor function. Nausea and vomiting
to opioids or any other contraindication for the use of
are the most common side effects and tramadol does
opioids, end stage renal disease, history of seizure or
not increase seizure incidence when compared to other
any abnormal laboratory tests that could interfere with
analgesic agents. Tramadol has been used clinically and
evaluated during the past 20 years with broad
The methodology and procedure of study had
indications leading to its widespread use.7
been cleared by the ethical committee and clinical
Ketorolac tromethamine is a member of the
research review committee, Mamata Dental College.
pyrrolo-pyrrole group of nonsteroidal anti-
All the individuals were well informed about the study,
inflammatory drugs (NSAIDs) which was previously
methodology and also about the visual analog scale
reported for the short term management of moderate
prior to tooth extraction. The individuals were
to severe pain. The primary molecular basis for anti-
unawared of the analgesic which they had taken during
inflammatory, antipyretic and analgesic effects of
the study. The drugs ketorolac and tramadol were
M M Shaik et al. Comparative study of Tramadol and Ketorolac in the pain management of third molar tooth extraction
procured from the hospital pharmacy and they have
The analgesic effect for group ‘B’ who were taken
been assigned a code. Patients were randomly assigned
ketorolac started within 30 mins and showed its’s
in either treatment groups with an assigned code.
maximum analgesic effect in 1st hour itself. The pain
The patients were divided into two groups
intensity scored on visual analog is 2.45 at 1st hour.
containing 75 patients in each group. All the codes of
But the effect was not sustained till the next dose. The
administered drugs were disclosed only after the pain
patients felt the pain in the 5th hour itself. The patients
assessment. The group ‘A’ received tramadol 50mg
scored ‘6.94’ in 5th hour and ‘7.34’ in 6th hour on
oral dose before the extraction and dose repeated after
visual analog scale. After the second dose, the pain
6 hours. The group ‘B’ received ketorolac 10mg oral
intensity was observed for every 6 hrs. At the end of
dose before the extraction and dose was repeated after
24 hours, the patient scored ‘2.98’ on visual analog
6hrs. Pain assessment was done by verbal rating using
scale. The ‘p’ values were less than 0.05 and were
Visual Analog Scale.10, 11 [0 – no pain, 2 - mild pain,
considered statistically significant (Table 1). 4 - tolerable, 6 – distressful pain, 8 – severe pain
According the observations, the analgesic effect
and 10 – totally disabling pain]. The pain
is reached quickly in group ‘B’ who received ketorolac.
assessment was started after the tooth extraction at
However, the duration of analgesia is more in group
time points of 30 min, 1, 2, 3, 4, 5, 6, 12, 18 and 24
‘A’ patients who received tramadol (Figure 1). Many
hrs. The patient’s vital signs including heart rate,
patients in group who received ketorolac complained
respiratory rate and blood pressure were recorded at
of pain before the dosing schedule time i.e. 6 hours.
every time point after the assessment of pain intensity.
The adverse effects in group ‘A’ who took
Statistical analyses were performed using Chi-square
tramadol were minimum and they were shown only in
8% of the patients. Major adverse effects seen in thisgroup are sweating (8%), sedation (5%) and decrease
in blood pressure (4%). But in group ‘B’ who were on
The majority of the patients scored an average
ketorolac, adverse effects were observed in 33%
pain intensity of ‘8.07’ on visual analog scale as the
patients. 33% patients reported the bleeding at the
maximum pain felt by them in their life time. The
extraction site and 20% patients reported the epigastric
analgesic effect for group ‘A’ who were taken tramadol
pain. The intensity of adverse effects here increased
started within 1st hour and reached the maximum
as dose increased. With the first dose of ketorolac,
analgesic effect in 3 hours. The average rating of pain
only 8% patients reported both epigastric pain and the
intensity is ‘1.12’ on visual analog scale for the
bleeding at the extraction site. (Table 2)
maximum analgesic effect felt at 3rd hour and with thefirst dose the analgesic effect sustained for 6 hours. Discussion
The analgesic effect of tramadol has been increased
Inspite of the spectacular advances in modern
for every six hours and at the end of the 24 hours, the
medicine, no single drug satisfied all the criteria of an
patients scored the pain intensity of ‘2.12’ on visual
ideal post extraction analgesic. Post extraction
analgesia can increase the patients comfort, decrease
Journal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1
the pain and stress after tooth extraction. The present
References
study was designed to assess and compare the efficacy,
Oladimeji A Akadiri, Ambrose E Obiechina.:
safety and the patient satisfaction of two most
Assessment of difficulty in third molar surgery-a
commonly clinically used analgesics tramadol and
systematic review. Oral Maxillofac Surg. 2009 (Apr);
ketorolac. Tramadol is a newer opioid with better
analgesic action without the risk of developement of
Capuzzi P ontebugnoli L M Vaccaro M A.: Extraction
tolerance and physical dependence. Now it has been
of impacted third molars. A longitudinal prospective
using very commonly for chronic pain. From theliterature it has been considered as safest postoperative
study on factors that affect postoperative recovery.
analgesic. 5, 12 Ketorolac is a most commonly used
Oral Surg Oral Med Oral Pathol. 1994 (Apr).; 77 (4) :
NSAID for the short term management of pain. Main
focus was on the study of pain intensity and the adverse
HUSSAIN AL-KHATEEB Taiseer; ALNAHAR Amir.:
effects of both the commonly used analgesics, tramadol
Pain Experience After Simple Tooth Extraction, Journal
and ketorolac. Safety of therapy was based on the
of oral and maxillofacial surgery. 2008 (May).; (66),
frequency of side effects and evolution of vital signs
recorded during the study. From the current study it
De Beer Jde V, Winemaker MJ, Donnelly GA, et al.:
has been proved that both the drugs are giving betteranalgesic effect. Ketorolac is showing its analgesic
Efficacy and safety of controlled-release oxycodone
effect very rapidly but the action sustained only up to
and standard therapies for postoperative pain after
4 hours (Figure 1). Where as tramadol’s analgesic
knee or hip replacement. Can J Surg. 2005; 48:277.
effect started after 1 hour and sustained for the longer
Recart A, Duchene D, White PF, et al.: Efficacyand safety
time i.e. more than 6 hours (Figure 1). The patients
of fast-track recovery strategy for patients undergoing
who received ketorolac also reported severe adverse
laparoscopic nephrectomy. J Endourol 2005; 19:1165.
effects like epigastric pain, bleeding at the tooth
Watcha MF, Issioui T, Klein KW, et al.: Costs and effect
extraction site, nausea and sweating. Tramadol had a
of rofecoxib, celecoxib, and otolaryngologic surgery.
bit marked effect on blood pressure and also causedsweating in few patients (Figure 2(a), 2(b), 2(c), 2(d). Pozos-Guillén Ade J, Martínez-Rider R, Aguirre-Conclusion Bañuelos P, et al.: Analgesic efficacy of tramadol by
The overall study profile proved that tramadol is a
route of administration in a clinical model of pain.
suitable and safe analgesic with longer duration of
Proc West Pharmacol Soc. 2005; 48: 61-4.
action and less adverse effects for relief of post-extraction pain after third molar extraction and is more
Zackova M, Taddei S, Calò P, et al.: Ketorolac vs
effective than ketorolac with a long sustained analgesic
tramadol in the treatment of postoperative pain during
action. The percentage of side effects was minimal. maxillofacial surgery. Minerva Anestesiol. 2001M M Shaik et al. Comparative study of Tramadol and Ketorolac in the pain management of third molar tooth extractionOng KS, Tan JM.:Preoperative intravenous tramadol11. Seymour RA.:The use of pain scales in assessing theversus ketorolac for preventing postoperative painefficacy of analgesics in post-operative dental painafter third molar surgery. Int J Oral MaxillofacEur J Clin Pharmacol. 1982;23(5):441-4.12. Stamer Um, Maier C, Grond S, Veh-Schmidt, Klaschik10. Melzack R.:The Mc Gill Pain Questionnaire: MajorE, Lehman KA.: Tramadol in the management of post-properties and scoring methods. 1975;277 – 99operative pain: a double-blind, placebo-and activedrug-controlled study. Eur J Ana. 1997;12(6):646-54. Table 1: Comparison of Pain intensities of Tramadol and Penatazocine Tramadol Ketorolac Time intervals at which Pain intensity is measured Mean ± SD Mean ± SD 1st Dose 2nd Dose 3rd Dose 4th Dose Journal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1Figure 1: Graphical representation – Comparison of pain intensities of Tramadol and Ketorolac M M Shaik et al. Comparative study of Tramadol and Ketorolac in the pain management of third molar tooth extractionTable 2: Side effects distribution of Tramadol and Pentazocine Tramadol Ketorolac Adverse Effects No of patients Percentage No of patients Percent with side with side effects* effects* After 1st Dose Sedation Sweating Bleeding at tooth extraction Diarrhoea Epigastric Pain Decrease in B.P. After 2nd Dose Sedation Sweating Bleeding at tooth extraction site Diarrhoea Epigastric Pain Decrease in B.P. 3rd Dose Sedation Sweating Bleeding at tooth extraction site Diarrhoea Epigastric Pain Decrease in B.P. 4th Dose Sedation Sweating Bleeding at tooth extraction site Diarrhoea Epigastric Pain Decrease in B.P. * Each group contains total number of 75 patients Journal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1Figure 2(a): Graphical representation – Comparison of Adverse effects of Tramadol and Ketorolac after 1st dose Figure 2(b): Graphical representation – Comparison of Adverse effects of Tramadol and Ketorolac after 2nd dose M M Shaik et al. Comparative study of Tramadol and Ketorolac in the pain management of third molar tooth extractionFigure 2(d): Graphical representation – Comparison of Adverse effects of Tramadol and Ketorolac after 4th dose
Methotrexate: Patient drug information Obtained from Uptodate. U.S. Brand Names: Rheumatrex®; Trexall™ Mexican Brand Names: Atrexel; Ledertrexate; Medsatrexate; Otaxem; Texate; Trixilem Pharmacologic Category: Antineoplastic Agent, Antimetabolite (Antifolate); Antirheumatic, Disease Modifying What key warnings should I know about before taking this medicine? • Your bone ma
Name: __________________________________________________ Street Address: ___________________________________________ City: _____________________________ Zip:___________________ Daytime Phone: _______________ Evening Phone: ___________ Email Address:____________________________________________ Highest Level of Education Completed: Current College students please fill out the following sectio