1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56
DENTOALVEOLAR SURGERY
Comparison of the Effects of Topical Ketamine and Tramadol on Postoperative Pain After Mandibular Molar Extraction Q7
Onur G€ on€ ul, DDS, PhD,* T€ ulin Satilmis¸, MD,y Alanur Ciftci, DDS,z Ayseg€ ul Sipahi, DDS, PhD,x Hasan Garip, DDS, PhD,k and Kamil G€ oker, DDS, PhD{ Purpose:
This study compared the analgesic efficacy of postoperative tramadol versus ketamine for preventing pain after mandibular molar extraction.
Patients and Methods:
Ninety patients who had undergone molar extraction were randomly divided into 3 groups: group T (tramadol 1 mg/kg), group K (ketamine 0.5 mg/kg), and group P (saline 2 mL). The treatment was applied to the extraction sockets using resorbable gelatin sponges. Pain after extraction was evaluated using a visual analog scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 hours postoperatively.
Results:
The VAS scores after extraction were statistically higher in group P than in either treatment group. Group K had the lowest pain intensity.
Conclusion: Q4
This study shows that topical tramadol and ketamine are effective alternatives for decreasing pain after molar extractions. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1-5, 2015 Pain is a major symptom after many dental procedures, especially tooth extractions, and its management is a challenging part of dentistry.1,2 For years researchers have sought the best analgesia after tooth extractions. Tramadol hydrochloride is a synthetic, centrally acting analgesic with a low affinity for opioid receptors.3 Structurally, it is related to codeine and morphine.3,4 Tramadol is effective for treating moderate to severe pain, including postsurgical, obstetric, and terminal cancer pain and pain of coronary origin. The analgesic effect arises from the modification of the transmission of pain impulses, because the drug inhibits monoamine reuptake. It has low addiction potential.5 The side effects of tramadol are more acceptable than those of traditional opioids and it is effective after dental procedures.6 Ketamine is a phencyclidine derivative that provides analgesia at sub-anesthetic doses.7 It can be adminis-
Q2
tered intravenously, intramuscularly, orally, or rectally.8 It is an N-methyl-D-aspartate receptor antagonist with opioid receptor activity and is an effective agent for neuropathic and nociceptive pain.9
Patients and Methods This comparative, prospective, randomized study enrolled 90 patients in the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Marmara University, Istanbul, Turkey. Ethics committee approval was obtained from the appropriate institution (approval no 154/6122011). Informed consent was obtained from the participating patients. To standardize the study, the groups were chosen from patients who had undergone elective unilateral mandibular molar extraction. The mean patient age was 24.4 years (range, 18 to 40 yr). The patients
Received from the Department of Oral and Maxillofacial Surgery,
G€ uzelbahc¸e B€ uy€ ukc¸iftlik Street, No 6, 34349 Nis¸antas¸ı, Istanbul,
Faculty of Dentistry, Marmara University, Istanbul, Turkey.
Turkey; e-mail: [email protected]
*---.
Received February 25 2015
y---. z---.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
x---.
0278-2391/15/00596-0
k---.
http://dx.doi.org/10.1016/j.joms.2015.05.012
Accepted May 12 2015
{---. Address correspondence and reprint requests to Dr G€ on€ ul: Department of Oral and Maxillofacial Surgery, Marmara University,
1 FLA 5.2.0 DTD YJOMS56820_proof 1 June 2015 7:07 pm CE AH
Q3
57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112
113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168
2
POSTOPERATIVE EFFECTS OF KETAMINE AND TRAMADOL
Pain after the extraction was evaluated using a visual analog scale (VAS). The patients were asked to score the overall pain at 0.5, 1, 2, 4, 6, 12, 24, and 48 hours using the VAS (0, no pain; 5, pain requiring analgesia; 10, excessive pain). Patients were asked to record the time and amount of analgesic taken after the extraction. The total analgesic consumption during the first 48 hours was recorded. Patients were asked to provide an overall evaluation of the pain experience on a 5-point Likert scale during the postsurgical followup visit 7 days after surgery (1, poor [maximum pain]; 2, fair; 3, good; 4, very good; 5, excellent [minimum pain]). No patient dropped out of the study. Statistical analysis was performed using NCSS 2007 and PASS 2008 statistical software (NCSS, Kaysville, UT). To evaluate the data, descriptive statistics (mean and standard deviation), 1-way analysis of variance, the Kruskal-Wallis test, and the Tukey honestly significant difference test were used. The results were considered significant if the probability was less than .05.
weighed less than 100 kg and were American Society of Anesthesiology status I.9 The study was doubly blinded and placebo controlled. Exclusion criteria were the use of sedatives, tranquilizers, or analgesic drugs 24 hours before treatment, a history of sensitivity to tramadol or ketamine, and the use of more than 3 cartridges of local anesthesia during the procedure. During the procedure, all patients were in a semisupine position. Electrocardiographic, noninvasive blood pressure, and peripheral oxygen saturation monitors were attached. Then, an inferior dental nerve block was achieved using with 2% articaine HCl with 1:100,000 epinephrine HCl (Ultracaine D-S Forte; Aventis, Bridgewater, NJ). The efficacy of the local anesthetic was assessed by verbal questioning and by gently probing the buccal and lingual surfaces of the mandibular molar. The mandibular molar was removed using a standard technique. After the procedure, the patients were randomly divided into 3 groups: group T (tramadol 1 mg/kg diluted with saline to 2 mL), group K (ketamine 0.5 mg/kg diluted with saline to 2 mL), and group P (saline 2 mL). The solutions were prepared by an anesthetic nurse and applied to the extraction sockets on resorbable gelatin sponges by the surgeon. The surgeon was blinded to the specific solution used. The time of application of local anesthesia was defined as time 0. The time of the start of the extraction procedure and the extraction time were recorded. Postoperative mean blood pressure, heart rate, peripheral oxygen saturation, and Ramsay scores of the patients were recorded every 10 minutes. The patients were questioned about side effects (burning, nausea, vomiting, weakness, and hallucinations) after the procedure.
Results Ninety patients (45 female and 45 male) were included in the study. Each group included 30 patients. The distributions of the groups are listed in Table 1. There were no statistical differences among the group variables, such as the duration of anesthesia or the duration of extraction. No complications were associated with the extraction procedure (Table 1). The VAS scores 0.5, 1, 2, 4, 6, 12, 24, and 48 hours after the extraction were statistically higher in group P than in groups T and K. During the first 6 hours, patients reported statistically lower pain intensity scores in groups K and T versus group P. At 12 hours, group K
Table 1. DISTRIBUTIONS OF GROUPS
Group Ketamine (Group K)
Age (yr) Height (cm) Weight (kg) Duration of anesthesia (minutes) Duration of extraction (minutes)
Tramadol (Group T)
Control (Group P)
Mean
SD
Mean
SD
Mean
SD
Test Value
df
P Value
24.00 168.73 68.93 5.97
5.153 7.965 10.998 1.273
24.17 171.83 70.87 5.67
5.207 7.992 9.005 0.844
24.57 170.63 66.50 5.63
4.116 8.286 9.748 0.809
0.760 1.122 1.451 0.385
2
2
.684* .33y .24y .825*
6.07
2.016
6.13
1.332
5.50
0.630
4.160
2
.125*
Abbreviation: SD, standard deviation. * By Kruskal-Wallis test. y By analysis of variance. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
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€ U € L ET AL GON
Table 2. VAS SCORES
Group Ketamine (Group K)
Tramadol (Group T)
Control (Group P)
VAS Scores (hr)
Mean
SD
Mean
SD
Mean
SD
Test Value
df
P Value*
0.5 1 2 4 6 12 24 48
0.00 0.00 0.20 0.50 1.07 0.20 0.17 0.10
0.000 0.000 0.551 0.900 1.112 0.407 0.379 0.548
0.00 0.10 0.30 0.63 0.70 0.80 0.90 0.03
0.000 0.305 0.702 1.159 1.119 1.064 0.712 0.183
0.00 5.00 1.93 1.03 2.73 1.23 1.47 0.00
0.000 1.174 0.740 0.183 0.785 0.898 0.681 0.000
0.000 80.097 57.170 21.465 39.844 20.638 40.702 1.012
2 2 2 2 2 2 2 2
1.000 .0001 .0001 .0001 .0001 .0001 .0001 .603
Abbreviations: SD, standard deviation; VAS, visual analog scale. * By Kruskal-Wallis test. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
had lower pain intensities than the other 2 groups. At 24 hours, group K had the lowest pain intensity and group T had less pain than group P. At 48 hours, there were no statistical differences among the groups (Table 2, Fig 1). The total consumption of analgesics was significantly greater in group P than in groups T and K (P = .0001). The time the first analgesic was taken was considerably sooner in group P than in the other groups. Patient satisfaction was significantly lower in group P than in the other groups (P = .011; Table 3). Considering the reported adverse effects, nausea was significantly more common in group T than in groups K and P (P = .013). There were no significant differences in vomiting (P = .129) or burning sensation (P = .2) among the 3 groups (Table 4).
Discussion Dental extraction constitutes trauma and the extraction of molars is more traumatic than that of other teeth and it induces acute moderate to severe pain. Nonsteroidal anti-inflammatory drugs and opioid analgesics can be used to relieve postoperative pain. To determine the best analgesic for postoperative pain after extractions, the authors compared the local application of tramadol and ketamine. These compounds showed good analgesic efficacy in preventing postoperative pain after extraction. Similar studies have examined pre- or postoperative administration of tramadol after surgery of the third molar. Ong and Seymour2 compared the analgesic efficacy of single-dose preoperative intravenous versus oral tramadol for preventing pain after third molar
print & web 4C=FPO
225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280
3
FIGURE 1. Change in pain score over time for each group. VAS, visual analog scale. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
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281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336
337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392
4
POSTOPERATIVE EFFECTS OF KETAMINE AND TRAMADOL
Table 3. SATISFACTION RATES
Group Ketamine (Group K)
First analgesic taken Total analgesic consumption Overall assessment
Tramadol (Group T)
Control (Group P)
Mean
SD
Mean
SD
Mean
SD
Test Value
df
P Value*
1.70 0.27 4.80
3.292 0.521 0.484
3.23 0.67 4.93
3.821 1.241 0.254
1.00 1.73 4.67
0.000 0.691 0.479
11.116 43.126 6.808
2 2 2
.004 .0001 .033
Abbreviation: SD, standard deviation. * By Kruskal-Wallis test. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
surgery and concluded that intravenous tramadol is superior to oral tramadol for preventing postoperative pain. Collins et al6 assessed the analgesic effect of tramadol for the relief of pain after dentoalveolar operations that involved the removal of bone and suturing. The treatment resulted in complete pain relief, and this continued for the next 2 days. No serious or unexpected adverse effects were reported and they concluded that tramadol is an effective analgesic after dentoalveolar operations. Pozos10 investigated the analgesic effects of tramadol given systemically, into the surgical site, or by the 2 routes, and placebo after extraction of an impacted mandibular third molar under local anesthesia. Pozos found that tramadol extends the duration of anesthesia when administered locally and systemically and improves the quality of postoperative analgesia. Pozos-Guillen Ade et al11 showed that the pre-emptive use of tramadol considerably decreased the consumption of analgesics, and the duration of anesthesia was longer when tramadol was
Table 4. REPORTED ADVERSE EFFECT
Nausea Absent Present Vomiting Absent Present Burning sensation Absent Present
n
%
c2
df
P Value*
70 20
77.8 22.2
27.778
1
.0001
88 2
97.8 2.2
82.178
1
.0001
84 6
93.3 6.7
67.600
1
.0001
* By Kruskal-Wallis test. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
injected into the surgical site after surgical extraction of an impacted mandibular third molar under local anesthesia. Another study also showed that the combination of intramuscular tramadol and injection of tramadol into the surgical site considerably decreased the requirement for paracetamol.12 Many previous studies have used ketamine as an anesthetic agent, whereas some have used it as an analgesic. Slatkin and Rhiner13 reported that ketamine decreased pain in a patient with radiation-induced oral mucositis; the ketamine was prescribed as an oral rinse for 1 week. Other studies used ketamine topically after tonsillectomy; the treatment produced an analgesic effect and decreased the need for rescue medication.14-16 Satilmis¸ et al12 investigated the efficacy of adding ketamine to local anesthetic agents to increase the duration of regional anesthesia and postoperative analgesia during surgical extraction of third molars. They concluded that the combination of a local anesthetic and sub-anesthetic doses of ketamine can produce good local anesthesia. The combination affords a comfortable procedure for the surgeon and the patient and provides good postoperative analgesia with less swelling and considerably less trismus. Unlike these previous studies, the authors used tramadol topically and found that it is an effective way to obtain analgesia after extraction. Although ketamine is known as an anesthetic agent, it also was used as an analgesic agent. Based on the VAS scores of the present patients, ketamine can be used as a topical analgesic. Local application of tramadol and ketamine after molar extraction is an effective alternative for decreasing pain after molar extractions. However, ketamine was more effective than tramadol. Nevertheless, because only a few studies have examined ketamine in postoperative dentoalveolar pain, further studies with more patients are needed. Q5
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€ U € L ET AL GON
449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469
5
References 1. Isiordia-Espinoza MA, de Jes us Pozos-Guillen A, Aragon-Martinez OH: Analgesic efficacy and safety of singledose tramadol and non-steroidal anti-inflammatory drugs in operations on the third molars: A systematic review and metaanalysis. Br J Oral Maxillofac Surg 52:775, 2014 2. Ong CK, Seymour RA: An evidence-based update of the use of analgesics in dentistry. Periodontol 2000. 46:143, 2008 3. Gopalraju P, Lalitha RM, Prasad K, et al: Comparative study of intravenous tramadol versus ketorolac for preventing postoperative pain after third molar surgery: A prospective randomized study. J Craniomaxillofac Surg 42:629, 2014 4. Cliff K: The analgesic efficacy of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery. J Oral Maxillofac Surg 63:1162, 2005 5. Scott LJ, Perry CM: Tramadol: A review of its use in perioperative pain. Drugs 60:139, 2000 6. Collins M, Young I, Sweeney P, et al: The effect of tramadol on dento-alveolar surgical pain. Br J Oral Maxillofac Surg 35:54, 1997 7. Kronenberg RH: Ketamine as an analgesic: Parenteral, oral, rectal, subcutaneous, transdermal and intranasal administration. J Pain Palliat Care Pharmacother 16:27, 2002
8. Haas D, Harper DG: Ketamine: A review of its pharmacologic properties and use in ambulatory anesthesia. Anesth Prog 39: 61, 1992 9. Keats AS: The ASA classification of physical status: A recapitulation. Anesthesiology 49:233, 1978 10. Pozos AJ: Tramadol administered in a combination of routes for reducing pain after removal of an impacted mandibular third molar. J Oral Maxillofac Surg 65:1633, 2007 11. Pozos-Guillen Ade J, Martınez-Rider R, Aguirre-Ba~ nuelos P, et al: Analgesic efficacy of tramadol by route of administration in a clinical model of pain. Proc West Pharmacol Soc 48:61, 2005 12. Satilmis¸ T, Garip H, Arpaci E, et al: Assessment of combined local anesthesia and ketamine for pain, swelling, and trismus after surgical extraction of third molars. J Oral Maxillofac Surg 67:1206, 2009 13. Slatkin NE, Rhiner M: Topical ketamine in the treatment of mucositis pain. Pain Med 4:298, 2003 14. Canbay O, Celebi N, Uzun S, et al: Topical ketamine and morphine for post-tonsillectomy pain. Eur J Anaesthesiol 25: 287, 2008 15. Tekelioglu UY, Apuhan T, Akkaya A, et al: Comparison of topical tramadol and ketamine in pain treatment after tonsillectomy. Paediatr Anaesth 23:496, 2013 16. Sawynok J: Topical and peripheral ketamine as an analgesic. Anesth Analg 119:170, 2014
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DENTOALVEOLAR SURGERY
Comparison of the Effects of Topical Ketamine and Tramadol on Postoperative Pain After Mandibular Molar Extraction Q7
Onur G€ on€ ul, DDS, PhD,* T€ ulin Satilmis¸, MD,y Alanur Ciftci, DDS,z Ayseg€ ul Sipahi, DDS, PhD,x Hasan Garip, DDS, PhD,k and Kamil G€ oker, DDS, PhD{ Purpose:
This study compared the analgesic efficacy of postoperative tramadol versus ketamine for preventing pain after mandibular molar extraction.
Patients and Methods:
Ninety patients who had undergone molar extraction were randomly divided into 3 groups: group T (tramadol 1 mg/kg), group K (ketamine 0.5 mg/kg), and group P (saline 2 mL). The treatment was applied to the extraction sockets using resorbable gelatin sponges. Pain after extraction was evaluated using a visual analog scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 hours postoperatively.
Results:
The VAS scores after extraction were statistically higher in group P than in either treatment group. Group K had the lowest pain intensity.
Conclusion: Q4
This study shows that topical tramadol and ketamine are effective alternatives for decreasing pain after molar extractions. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1-5, 2015 Pain is a major symptom after many dental procedures, especially tooth extractions, and its management is a challenging part of dentistry.1,2 For years researchers have sought the best analgesia after tooth extractions. Tramadol hydrochloride is a synthetic, centrally acting analgesic with a low affinity for opioid receptors.3 Structurally, it is related to codeine and morphine.3,4 Tramadol is effective for treating moderate to severe pain, including postsurgical, obstetric, and terminal cancer pain and pain of coronary origin. The analgesic effect arises from the modification of the transmission of pain impulses, because the drug inhibits monoamine reuptake. It has low addiction potential.5 The side effects of tramadol are more acceptable than those of traditional opioids and it is effective after dental procedures.6 Ketamine is a phencyclidine derivative that provides analgesia at sub-anesthetic doses.7 It can be adminis-
Q2
tered intravenously, intramuscularly, orally, or rectally.8 It is an N-methyl-D-aspartate receptor antagonist with opioid receptor activity and is an effective agent for neuropathic and nociceptive pain.9
Patients and Methods This comparative, prospective, randomized study enrolled 90 patients in the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Marmara University, Istanbul, Turkey. Ethics committee approval was obtained from the appropriate institution (approval no 154/6122011). Informed consent was obtained from the participating patients. To standardize the study, the groups were chosen from patients who had undergone elective unilateral mandibular molar extraction. The mean patient age was 24.4 years (range, 18 to 40 yr). The patients
Received from the Department of Oral and Maxillofacial Surgery,
G€ uzelbahc¸e B€ uy€ ukc¸iftlik Street, No 6, 34349 Nis¸antas¸ı, Istanbul,
Faculty of Dentistry, Marmara University, Istanbul, Turkey.
Turkey; e-mail: [email protected]
*---.
Received February 25 2015
y---. z---.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
x---.
0278-2391/15/00596-0
k---.
http://dx.doi.org/10.1016/j.joms.2015.05.012
Accepted May 12 2015
{---. Address correspondence and reprint requests to Dr G€ on€ ul: Department of Oral and Maxillofacial Surgery, Marmara University,
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Q3
57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112
113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168
2
POSTOPERATIVE EFFECTS OF KETAMINE AND TRAMADOL
Pain after the extraction was evaluated using a visual analog scale (VAS). The patients were asked to score the overall pain at 0.5, 1, 2, 4, 6, 12, 24, and 48 hours using the VAS (0, no pain; 5, pain requiring analgesia; 10, excessive pain). Patients were asked to record the time and amount of analgesic taken after the extraction. The total analgesic consumption during the first 48 hours was recorded. Patients were asked to provide an overall evaluation of the pain experience on a 5-point Likert scale during the postsurgical followup visit 7 days after surgery (1, poor [maximum pain]; 2, fair; 3, good; 4, very good; 5, excellent [minimum pain]). No patient dropped out of the study. Statistical analysis was performed using NCSS 2007 and PASS 2008 statistical software (NCSS, Kaysville, UT). To evaluate the data, descriptive statistics (mean and standard deviation), 1-way analysis of variance, the Kruskal-Wallis test, and the Tukey honestly significant difference test were used. The results were considered significant if the probability was less than .05.
weighed less than 100 kg and were American Society of Anesthesiology status I.9 The study was doubly blinded and placebo controlled. Exclusion criteria were the use of sedatives, tranquilizers, or analgesic drugs 24 hours before treatment, a history of sensitivity to tramadol or ketamine, and the use of more than 3 cartridges of local anesthesia during the procedure. During the procedure, all patients were in a semisupine position. Electrocardiographic, noninvasive blood pressure, and peripheral oxygen saturation monitors were attached. Then, an inferior dental nerve block was achieved using with 2% articaine HCl with 1:100,000 epinephrine HCl (Ultracaine D-S Forte; Aventis, Bridgewater, NJ). The efficacy of the local anesthetic was assessed by verbal questioning and by gently probing the buccal and lingual surfaces of the mandibular molar. The mandibular molar was removed using a standard technique. After the procedure, the patients were randomly divided into 3 groups: group T (tramadol 1 mg/kg diluted with saline to 2 mL), group K (ketamine 0.5 mg/kg diluted with saline to 2 mL), and group P (saline 2 mL). The solutions were prepared by an anesthetic nurse and applied to the extraction sockets on resorbable gelatin sponges by the surgeon. The surgeon was blinded to the specific solution used. The time of application of local anesthesia was defined as time 0. The time of the start of the extraction procedure and the extraction time were recorded. Postoperative mean blood pressure, heart rate, peripheral oxygen saturation, and Ramsay scores of the patients were recorded every 10 minutes. The patients were questioned about side effects (burning, nausea, vomiting, weakness, and hallucinations) after the procedure.
Results Ninety patients (45 female and 45 male) were included in the study. Each group included 30 patients. The distributions of the groups are listed in Table 1. There were no statistical differences among the group variables, such as the duration of anesthesia or the duration of extraction. No complications were associated with the extraction procedure (Table 1). The VAS scores 0.5, 1, 2, 4, 6, 12, 24, and 48 hours after the extraction were statistically higher in group P than in groups T and K. During the first 6 hours, patients reported statistically lower pain intensity scores in groups K and T versus group P. At 12 hours, group K
Table 1. DISTRIBUTIONS OF GROUPS
Group Ketamine (Group K)
Age (yr) Height (cm) Weight (kg) Duration of anesthesia (minutes) Duration of extraction (minutes)
Tramadol (Group T)
Control (Group P)
Mean
SD
Mean
SD
Mean
SD
Test Value
df
P Value
24.00 168.73 68.93 5.97
5.153 7.965 10.998 1.273
24.17 171.83 70.87 5.67
5.207 7.992 9.005 0.844
24.57 170.63 66.50 5.63
4.116 8.286 9.748 0.809
0.760 1.122 1.451 0.385
2
2
.684* .33y .24y .825*
6.07
2.016
6.13
1.332
5.50
0.630
4.160
2
.125*
Abbreviation: SD, standard deviation. * By Kruskal-Wallis test. y By analysis of variance. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
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€ U € L ET AL GON
Table 2. VAS SCORES
Group Ketamine (Group K)
Tramadol (Group T)
Control (Group P)
VAS Scores (hr)
Mean
SD
Mean
SD
Mean
SD
Test Value
df
P Value*
0.5 1 2 4 6 12 24 48
0.00 0.00 0.20 0.50 1.07 0.20 0.17 0.10
0.000 0.000 0.551 0.900 1.112 0.407 0.379 0.548
0.00 0.10 0.30 0.63 0.70 0.80 0.90 0.03
0.000 0.305 0.702 1.159 1.119 1.064 0.712 0.183
0.00 5.00 1.93 1.03 2.73 1.23 1.47 0.00
0.000 1.174 0.740 0.183 0.785 0.898 0.681 0.000
0.000 80.097 57.170 21.465 39.844 20.638 40.702 1.012
2 2 2 2 2 2 2 2
1.000 .0001 .0001 .0001 .0001 .0001 .0001 .603
Abbreviations: SD, standard deviation; VAS, visual analog scale. * By Kruskal-Wallis test. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
had lower pain intensities than the other 2 groups. At 24 hours, group K had the lowest pain intensity and group T had less pain than group P. At 48 hours, there were no statistical differences among the groups (Table 2, Fig 1). The total consumption of analgesics was significantly greater in group P than in groups T and K (P = .0001). The time the first analgesic was taken was considerably sooner in group P than in the other groups. Patient satisfaction was significantly lower in group P than in the other groups (P = .011; Table 3). Considering the reported adverse effects, nausea was significantly more common in group T than in groups K and P (P = .013). There were no significant differences in vomiting (P = .129) or burning sensation (P = .2) among the 3 groups (Table 4).
Discussion Dental extraction constitutes trauma and the extraction of molars is more traumatic than that of other teeth and it induces acute moderate to severe pain. Nonsteroidal anti-inflammatory drugs and opioid analgesics can be used to relieve postoperative pain. To determine the best analgesic for postoperative pain after extractions, the authors compared the local application of tramadol and ketamine. These compounds showed good analgesic efficacy in preventing postoperative pain after extraction. Similar studies have examined pre- or postoperative administration of tramadol after surgery of the third molar. Ong and Seymour2 compared the analgesic efficacy of single-dose preoperative intravenous versus oral tramadol for preventing pain after third molar
print & web 4C=FPO
225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280
3
FIGURE 1. Change in pain score over time for each group. VAS, visual analog scale. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
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Q6
281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336
337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392
4
POSTOPERATIVE EFFECTS OF KETAMINE AND TRAMADOL
Table 3. SATISFACTION RATES
Group Ketamine (Group K)
First analgesic taken Total analgesic consumption Overall assessment
Tramadol (Group T)
Control (Group P)
Mean
SD
Mean
SD
Mean
SD
Test Value
df
P Value*
1.70 0.27 4.80
3.292 0.521 0.484
3.23 0.67 4.93
3.821 1.241 0.254
1.00 1.73 4.67
0.000 0.691 0.479
11.116 43.126 6.808
2 2 2
.004 .0001 .033
Abbreviation: SD, standard deviation. * By Kruskal-Wallis test. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
surgery and concluded that intravenous tramadol is superior to oral tramadol for preventing postoperative pain. Collins et al6 assessed the analgesic effect of tramadol for the relief of pain after dentoalveolar operations that involved the removal of bone and suturing. The treatment resulted in complete pain relief, and this continued for the next 2 days. No serious or unexpected adverse effects were reported and they concluded that tramadol is an effective analgesic after dentoalveolar operations. Pozos10 investigated the analgesic effects of tramadol given systemically, into the surgical site, or by the 2 routes, and placebo after extraction of an impacted mandibular third molar under local anesthesia. Pozos found that tramadol extends the duration of anesthesia when administered locally and systemically and improves the quality of postoperative analgesia. Pozos-Guillen Ade et al11 showed that the pre-emptive use of tramadol considerably decreased the consumption of analgesics, and the duration of anesthesia was longer when tramadol was
Table 4. REPORTED ADVERSE EFFECT
Nausea Absent Present Vomiting Absent Present Burning sensation Absent Present
n
%
c2
df
P Value*
70 20
77.8 22.2
27.778
1
.0001
88 2
97.8 2.2
82.178
1
.0001
84 6
93.3 6.7
67.600
1
.0001
* By Kruskal-Wallis test. G€ on€ ul et al. Postoperative Effects of Ketamine and Tramadol. J Oral Maxillofac Surg 2015.
injected into the surgical site after surgical extraction of an impacted mandibular third molar under local anesthesia. Another study also showed that the combination of intramuscular tramadol and injection of tramadol into the surgical site considerably decreased the requirement for paracetamol.12 Many previous studies have used ketamine as an anesthetic agent, whereas some have used it as an analgesic. Slatkin and Rhiner13 reported that ketamine decreased pain in a patient with radiation-induced oral mucositis; the ketamine was prescribed as an oral rinse for 1 week. Other studies used ketamine topically after tonsillectomy; the treatment produced an analgesic effect and decreased the need for rescue medication.14-16 Satilmis¸ et al12 investigated the efficacy of adding ketamine to local anesthetic agents to increase the duration of regional anesthesia and postoperative analgesia during surgical extraction of third molars. They concluded that the combination of a local anesthetic and sub-anesthetic doses of ketamine can produce good local anesthesia. The combination affords a comfortable procedure for the surgeon and the patient and provides good postoperative analgesia with less swelling and considerably less trismus. Unlike these previous studies, the authors used tramadol topically and found that it is an effective way to obtain analgesia after extraction. Although ketamine is known as an anesthetic agent, it also was used as an analgesic agent. Based on the VAS scores of the present patients, ketamine can be used as a topical analgesic. Local application of tramadol and ketamine after molar extraction is an effective alternative for decreasing pain after molar extractions. However, ketamine was more effective than tramadol. Nevertheless, because only a few studies have examined ketamine in postoperative dentoalveolar pain, further studies with more patients are needed. Q5
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€ U € L ET AL GON
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5
References 1. Isiordia-Espinoza MA, de Jes us Pozos-Guillen A, Aragon-Martinez OH: Analgesic efficacy and safety of singledose tramadol and non-steroidal anti-inflammatory drugs in operations on the third molars: A systematic review and metaanalysis. Br J Oral Maxillofac Surg 52:775, 2014 2. Ong CK, Seymour RA: An evidence-based update of the use of analgesics in dentistry. Periodontol 2000. 46:143, 2008 3. Gopalraju P, Lalitha RM, Prasad K, et al: Comparative study of intravenous tramadol versus ketorolac for preventing postoperative pain after third molar surgery: A prospective randomized study. J Craniomaxillofac Surg 42:629, 2014 4. Cliff K: The analgesic efficacy of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery. J Oral Maxillofac Surg 63:1162, 2005 5. Scott LJ, Perry CM: Tramadol: A review of its use in perioperative pain. Drugs 60:139, 2000 6. Collins M, Young I, Sweeney P, et al: The effect of tramadol on dento-alveolar surgical pain. Br J Oral Maxillofac Surg 35:54, 1997 7. Kronenberg RH: Ketamine as an analgesic: Parenteral, oral, rectal, subcutaneous, transdermal and intranasal administration. J Pain Palliat Care Pharmacother 16:27, 2002
8. Haas D, Harper DG: Ketamine: A review of its pharmacologic properties and use in ambulatory anesthesia. Anesth Prog 39: 61, 1992 9. Keats AS: The ASA classification of physical status: A recapitulation. Anesthesiology 49:233, 1978 10. Pozos AJ: Tramadol administered in a combination of routes for reducing pain after removal of an impacted mandibular third molar. J Oral Maxillofac Surg 65:1633, 2007 11. Pozos-Guillen Ade J, Martınez-Rider R, Aguirre-Ba~ nuelos P, et al: Analgesic efficacy of tramadol by route of administration in a clinical model of pain. Proc West Pharmacol Soc 48:61, 2005 12. Satilmis¸ T, Garip H, Arpaci E, et al: Assessment of combined local anesthesia and ketamine for pain, swelling, and trismus after surgical extraction of third molars. J Oral Maxillofac Surg 67:1206, 2009 13. Slatkin NE, Rhiner M: Topical ketamine in the treatment of mucositis pain. Pain Med 4:298, 2003 14. Canbay O, Celebi N, Uzun S, et al: Topical ketamine and morphine for post-tonsillectomy pain. Eur J Anaesthesiol 25: 287, 2008 15. Tekelioglu UY, Apuhan T, Akkaya A, et al: Comparison of topical tramadol and ketamine in pain treatment after tonsillectomy. Paediatr Anaesth 23:496, 2013 16. Sawynok J: Topical and peripheral ketamine as an analgesic. Anesth Analg 119:170, 2014
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