Battista Grossi G. 2007.pdf

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J Oral Maxillofac Surg65:901-917, 2007

Assessing Postoperative Discomfort After

Third Molar Surgery: A Prospective Study

Giovanni Battista Grossi, MD, DMD, DDS,*

Carlo Maiorana, MD, DDS,

Rocco Alberto Garramone, MD, DDS,

Andrea Borgonovo, DMD, MD, Luca Creminelli, DDS,

and Franco Santoro, MD, DDS

Purpose: The purpose of this study was to identify the risk factors for severe discomfort aftermandibular third molar surgery and to assess the validity of the Postoperative Symptom Severity (PoSSe)scale.

Patients and Methods: In a 2-year prospective study, a total of 255 unilateral impacted mandibularthird molar teeth were surgically removed under local anesthesia by 3 surgeons. Standardized surgical

and analgesic protocols were followed. At the review appointment, 1 week after surgery, all patients

returned a completed follow-up questionnaire (PoSSe scale) and were evaluated clinically for postoper-ative pain (number of painkillers taken) and trismus (differences in mouth opening). Sixteen predictive

variables were evaluated using stepwise logistic regression analysis to identify the risk factors associatedwith severe discomfort.

Results: Severe postoperative discomfort was predicted by these independent variables: gender,tobacco use, ramus relationship/space available, and antibiotic prophylaxis. Oral contraceptive use andoperation time were not identified as risk factors. The patients perceptions of the severity of symptoms(PoSSe scale score) was strongly correlated with clinical assessment of trismus (r 0.54) and pain (r0.42).

Conclusion: The PoSSe scale resulted in a valid and responsive measure of the severity of symptomsafter surgical extraction of lower third molars and reflected the clinical severity of the postoperativediscomfort. From a patients perspective, operative factors had little bearing on the quality of life after

removal of mandibular third molars.2007 American Association of Oral and Maxillofacial Surgeons

J Oral Maxillofac Surg 65:901-917, 2007

The surgical removal of impacted mandibular third

molars is one of the most commonly performed

dentoalveolar procedures in oral and maxillofacial

surgery and is associated with various postopera-

tive sequelae. Permanent nerve damage and seriousinfections are the most severe complications fol-lowing third molar extractions, but the rate of suchcomplications is low.1-4 Pain, trismus, and swellingare the most common postoperative complaintsand influence the patients quality of life in the daysfollowing surgery.5,6 Moreover, removal of third

molar is so common that the population morbidityof such minor complications may be significant.

Surgeons perceptions of the consequences of thirdmolar surgery on their patients quality of lifeshowsignificant differences from those of patients.7 Overthe past 3 decades, the use of patient-centeredoutcome scales in general medicine and surgery hasincreased substantially, but has only recently beenused in oral surgery.8,9 To date, there has been littlepublished on patients perceptions on quality of lifeand risk factors for severe discomfort after removal

of a third molar.5-7,9-13

Received from the Department of Oral Surgery, School of Dentistry,

University of Milan, Milan, Italy.

*Clinical Assistant Profesor.

Associate Professor.

Resident.

Resident.

Clinical Assistant Professor.

Department Head.

Address correspondence and reprint requests to Dr Grossi: Oral

Surgery, School of Dentistry, Istituti Clinici di Perfezionamento, Via

Commenda n10, 20122 Milano, Italy; e-mail: Giovanni.Grossi@

unimi.it or [email protected]

2007 American Association of Oral and Maxillofacial Surgeons

0278-2391/07/6505-0013$32.00/0

doi:10.1016/j.joms.2005.12.046

901


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The aim of this study was:

1) To measure patients perceptions of changes intheir quality of life after mandibular third molarsurgery with a specific questionnaire (PoSSescale).13

2) To measure the clinical severity of trismus and

pain (differences in mouth opening and totalanalgesic consumption).

3) To identify preoperative and intraoperative risk

factors for severe postoperative discomfort.4) To assess the clinical validity of the PoSSe scale.

Patients and Methods

Between September 2002 and September 2004,at the Oral Surgery Department, I.C.P. Hospital,University of Milan (Italy), 213 consecutive patients

who had 266 extractions of mandibular third mo-

lars were prospectively studied. Fifty-three patientswho needed bilateral extractions had their teethremoved on separate occasions with at least 1month between them. Only 1 lower third molar

was removed at each operation and all teeth werepartially or completely covered by mucosa. Oneinclusion criterion for this study was that a muco-periosteal flap was to be raised during the opera-tion, so 11 molars were excluded from analysis and

a total of 255 mandibular third molars were there-fore available for analysis.

Participants were healthy individuals with no sys-

temic diseases or history of treatment for psychiat-ric problems. The patients were not taking anymedications, except for females who regularly tookoral contraceptives. Exclusion criteria included pa-tients who were pregnant or lactating. All patients

were free of caries, extensive periodontal disease,

pain, or other inflammatory symptoms at the timeof operation. Patients who were already taking an-timicrobials or had done so up to 2 weeks prior

were excluded. Informed written consent was ob-tained from all patients before they were includedin this study.

DATA COLLECTION

At the initial visit and at the follow-up on the sev-enth postoperative day, the information was recordedby a single clinical examiner: the surgeons that hadoperated on the patients were never involved in thepreoperative or postoperative assessment.

Preoperative Assessment

After consenting to participate in the study, thefollowing data were recorded: name, age, gender, siteof surgery, current tobacco and oral contraceptives

use, reasons for seeking third molar removal, and

maximum interincisal distance. Third molar position

was evaluated on the presurgical panoramic radio-graph using Winters and Pell and Gregory classifica-tion (Table 1).

Patients were scheduled for operation with no cor-relation between patient and surgeon, so that a ran-dom surgeon operated on the patient.

Medications

Patients were randomly allocated into 2 groups. Inthe first group (n 119), prophylactic preoperativeoral antibiotic was administered with 2 g amoxicillin/clavulanic acid 1 hour before surgery (Augmentin;GlaxoSmithKline, Verona, Italy). The second group(n 136) received no antibiotic medication and

served as the control. The surgeons were unawarewhether the prophylaxis was given or not.

A mouth rinse with 15 mL of 0.2% chlorhexidinesolution (Dentosan; Pfizer Consumer Healthcare,Rome, Italy) for 1 minute was used before surgery andimmediately after the operation. The day after sur-gery, patients began home use of the chlorhexidinesolution twice a day for 1 week.

Table 1. DESCRIPTIVE STATISTICS FORPREOPERATIVE VARIABLES

Preoperative Variables Category n %

Age (yrs) 22 63 24.7Average (27.04) 2329 117 45.9Range (1467) 29 75 29.4

Gender M 120 47.1

F 135 52.9Tobacco use Yes 76 29.8

No 179 70.2Oral contraceptive

useYes 45 33.3No 90 66.7

Antibiotic prophylaxis Yes 119 46.7No 136 53.3

Indication for removal Infection 79 31.0Periodontal disease 19 7.4Prophylactic removal 80 31.4Orthodontic reason 13 5.1Caries 37 14.5Atypical facial pain 27 10.6

Radiographic findingsNo. of roots Multiple 161 63.1

Singular 90 35.3Incomplete 4 1.6

Spatial relationship Distoangular 52 20.4Horizontal 59 23.2Vertical 72 28.2Mesioangular 72 28.2

Depth Level A (high) 43 16.9Level B (medium) 166 65.1Level C (deep) 46 18.0

Ramus relationship/space available

Class I (sufficient) 9 3.5Class II (reduced) 217 85.1Class III (none) 29 11.4

Grossi et al. Assessing Discomfort After Third Molar Surgery.J Oral Maxillofac Surg 2007.

902 ASSESSING DISCOMFORT AFTER THIRD MOLAR SURGERY


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Oral Coefferalgan (paracetamol 500 mg with co-deine 30 mg; Bristol-Myers Squibb, Sermoneta, Italy)

was immediately given after the surgery and was pre-scribed to be taken as required for pain relief (maxi-mum, 6 tablets daily). Patients were instructed not totake any drugs other than those prescribed and not to

seek medical help elsewhere for postoperative prob-lems.

Surgery

A total of 3 surgeons with more than 5 yearsdentoalveolar training, assisted by training house sur-geons, performed the surgeries. Each patient had sim-

ilar surgical procedures, in the same operating roomand under similar conditions, using mepivacaine 2%

with epinephrine 1:100.000 as local anesthetic (2%Carbocaine; AstraZeneca, Milan, Italy). No concomi-

tant medication was used during surgery other thanthe local anesthetic. Access to the third molar wasachieved from the buccal aspect and bone was re-moved with a round bur in a straight handpiece under

continuous irrigation with sterile saline solution. Ifnecessary, sectioning of crown and roots was per-formed with a fissure bur. After tooth extraction, thealveolus was inspected, curetted for granulation tis-sue removal, and irrigated with sterile saline solution.

A 4/0 silk suture was used to close the wound without

tension. An ice pack was then applied to the patientsface for 20 minutes.

Immediately after the operation, details of the pro-cedure were recorded, including the duration of sur-gery in minutes (from the first incision to insertion ofthe last suture) (Table 2).

Patients were given the usual postoperative instruc-

tions and received 2 questionnaires, after being in-

structed in their use: the PoSSe scale13 and a 9-point

scale to record pain levels.14

Postoperative Assessment

All patients returned 1 week after the operation to

have their sutures removed: the examiner was the

same as the one who assessed them preoperatively.Trismus was assessed by measuring the differences

in mouth opening (interincisal distance preopera-

tively and on postsurgery day 7).

The patients pain level were assessed with a

9-point visual analog scale anchored by the verbal

descriptors no pain (point 0) and very severe pain

(point 8).14 Patients were advised to take the analge-

sic tablet as soon as their pain reached a moderate

level. They were asked to enter their pain level and

the time at which the analgesic was taken, and then

make no further recordings.

The PoSSe scale13

was designed to assess the pa-tients perception of adverse effects in 7 subscales:

eating, speech, sensation, appearance, pain, sickness,

and interference with daily activities. A score was

assigned to the possible responses to each forced

question. The scores of the responses to each ques-

tion were summed. These scores represent a percent-

age, so that a patient completing the questionnaire

and ticking the most severe response category for

each question would score 100%. A patient ticking

the least severe response category for each question

would score 0%.

Table 2. DESCRIPTIVE STATISTICS FOR OPERATIVE VARIABLES

Operative Variables Category n %

Surgeon 1 50 19.62 124 48.63 81 31.8

Assistant surgeon Clinical dental student 133 52.2

Resident 78 30.6Specialist training 44 17.2

Flap design Envelope flap 59 23.1Vestibular triangular flap 48 18.9Vestibular trapezoidal flap 148 58.0

Bone removal Yes 200 78.4No 55 21.6

Extraction difficulty Elevator/forceps alone 49 19.2Bone removal/tooth sectioning 46 18.0Bone removal tooth/root sectioning 129 50.6Extremely difficult 31 12.2

Operation time (min) 10 49 19.21120 83 32.52130 69 27.130 54 21.2

Grossi et al. Assessing Discomfort After Third Molar Surgery. J Oral Maxillofac Surg 2007.

GROSSI ET AL 903


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Table 3. DESCRIPTIVE STATISTICS AND ANALYSIS OF VARIANCE (1-WAY ANOVA) OF INDEPENDENT VARIABLESVERSUS FULL POSSESCALE

Independent Variables (Preoperative andOperative)

Dependent Variable Full PoSSe Scale

PValueRange (min) Range (max) Mean Median

Age (yrs)22 7.13 61.88 32.70 33.38 .092329 5.11 81.65 36.12 34.4829 5.38 67.93 37.64 35.83

GenderM 7.13 67.89 33.62 33.09 .01F 5.11 81.65 37.59 37.09

Tobacco useYes 9.91 67.89 37.76 36.35 .11No 5.11 81.65 34.85 33.62

Oral contraceptive useYes 5.11 60.88 34.88 36.01 .11No 5.38 81.65 38.95 37.60

Antibiotic prophylaxisYes 5.38 62.64 32.89 31.61 .001No 5.11 81.65 38.20 37.01

Indication for removalInfection 11.21 81.65 36.16 35.09 .78Periodontal disease 15.74 62.64 35.70 32.27Prophylactic removal 5.11 66.28 35.97 35.78Orthodontics reason 20.49 67.93 38.62 38.59Caries 5.38 60.88 32.83 32.16Atypical facial pain 14.81 60.64 36.27 33.46

Number of rootsMultiple 5.11 67.93 35.34 34.46 .75Singular 7.13 81.65 36.51 35.75Incomplete 20.49 44.79 33.23 33.82

Spatial relationshipDistoangular 14.97 81.65 38.28 36.34 .44Horizontal 5.38 64.16 34.22 33.62Vertical 5.11 67.89 35.61 34.60

Mesioangular 7.13 61.88 35.21 34.07DepthLevel A (high) 11.21 55.04 32.72 30.99 .27Level B (medium) 5.11 81.65 36.46 35.59Level C (deep) 7.13 62.64 35.84 35.94

Ramus relationship/space availableClass I (sufficient) 17.87 41.13 31.22 33.46 .002Class II (reduced) 5.11 81.65 34.85 33.62Class III (none) 25.59 67.93 43.60 43.52

Surgeon1 7.13 62.64 32.56 31.35 .062 8.01 81.65 37.62 35.783 5.11 67.93 34.76 33.83

Assistant surgeonClinical dental student 7.13 81.65 35.70 34.43 .70

Resident 8.01 67.89 36.51 35.40Specialist training 5.11 67.93 34.38 33.49

Flap designEnvelope flap 5.11 56.46 32.07 31.41 .06Vestibular triangular flap 9.01 67.93 36.80 35.77Vestibular trapezoidal flap 5.38 81.65 36.82 34.56

Bone removalYes 5.38 81.65 36.80 34.68 .01No 5.11 56.46 31.78 32.02

Extraction difficultyElevator/forceps alone 5.11 56.46 31.97 32.02 .11Bone removal/tooth sectioning 10.27 81.65 38.29 35.70Bone removal tooth/root sectioning 5.38 67.93 35.79 34.43Extremely difficult 7.13 62.64 37.55 36.01




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Study Variables, Data Management,

and Analysis

The set of predictor variables was divided into 2groups: preoperative and operative variables (Tables1and 2).

The outcome variables were:

1) PoSSe score (derived from the PoSSe scale byadding the responses to each of the individualquestions).

2) Trismus (range of opening measured preopera-tively and on postsurgery day 7).

3) Pain (total analgesic consumption).

Data were entered into a spreadsheet (Excel; Mi-

crosoft, Inc, Redmond, WA) over the course of thestudy. With use of a statistical software package (SPSSfor Windows, version 12.0; SPSS Inc, Chicago, IL,

2003), descriptive statistics were computed for all ofthe study variables.All pertinent data were subsequently analyzed with

the 1-sample Kolmogorov-Smirnov test with respectto normality.

According to normality, initial statistical analyses

used parametric (1-way ANOVA) or nonparametrictest (Mann-WhitneyUtest or Kruskal-Wallis rank test)to measure the association between each predictor

variable (preoperative and operative) and outcomevariables (full PoSSe score, single PoSSe subscales,Trismus, and Pain). To measure the association be-tween the predictor and outcome variables while con-

trolling for confounders, a logistic regression modelwas used. Biologically relevant variables (age and gen-

der) and variables that had P .20 in the initialanalyses were entered into logistic regression modelas independent variables. All parameters used as out-come variables were dichotomized before enteringthe logistic regression: scores with a value of themedian value were recorded as 0, those of themedian value were recorded as 1. The data wereallowed to enter the model using backward selection

with the significance level to remove set at 0.1. Pear-

son 2 test was performed to test the goodness of fit

of the final model. Spearmans rank correlation coef-ficient was used to assess the correlation between theoutcome variables.

A value of P .05 was accepted as statisticallysignificant.

Results

Two hundred fifty-five patients (135 females, 120males) aged 14 to 67 years (average, 27.04 years)representing 255 extraction sites of mandibular thirdmolars were entered into this study. The descriptivestatistics for the sample are summarized in Tables 1and2.

RISK FACTORS FOR SEVERE DISCOMFORT

(MEASURED WITH THE POSSESCALE)

The mean PoSSe score (SD) was 35.72 13.54

(range, 5.1181.65). The results of descriptive statis-tics and of analysis of variance are shown in Table 3.The logistic regression analysis revealed risk factors

for severe discomfort (Table 4). Only 4 out of 16independent variables, all preoperative, were signifi-cant indicators for severe discomfort: gender, tobacco

use, antibiotic prophylaxis, and ramus relationship/space available.

Females had twice the odds of males of severediscomfort (odds ratio [OR] 2.07; P .01). Espe-cially, females were found to be at 6 times higherrisk of feeling sickness (OR 6.20; P .000) thanmales, and had a 2 to 2.5 times higher risk of

experiencing interference with daily activities,problems in eating and speaking, and changes of

appearance (Table 5).Smokers were found to have a higher risk for re-

porting more severe discomfort (OR 1.86; P .04),Patients who did not receive prophylactic antibioticsalso reported more discomfort (OR 2.05; P .007).

Finally, when evaluating the radiographic findings,the ramus relationship/space available was the only

variable found to increase the risk of severe discom-fort. If the third molar had insufficient space available

in relation to the ramus it was more likely that the

Table 3. (Contd)


Dependent Variable Full PoSSe Scale

PValueRange (min) Range (max) Mean Median

Operation time (min)10 5.11 81.65 33.05 32.76 .491120 5.38 67.93 36.08 34.432130 9.91 60.88 36.44 35.5630 7.13 62.64 36.67 34.45

Total 5.11 81.65 35.72 34.46


GROSSI ET AL 905


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patient scored high on the PoSSe scale than if thethird molar had sufficient space available (Class III,

OR 6.24, P .04; Class II, OR 2.18, P .34).

RISK FACTORS FOR TRISMUS

The mean difference of mouth opening (SD) was8.9 mm 8.2 (range, 0.036.0). Details of descriptivestatistics and nonparametric tests are shown inTable 6.

Like that found in the precedent logistic regressionmodel, gender, antibiotic prophylaxis, smoking hab-its, and ramus relationship/space available werestatistically significant predictors of severe trismus(Table 7). Moreover, in this model there was a higherrisk of trismus if the molar was deeply impacted orthe patients were over 23 years of age.

Finally, 2 operative variables were found to bestatistically significant predictors of the occurrence of

severe trismus: bone removal and surgeon.

RISK FACTORS FOR PAIN

The mean number of analgesic tablets taken post-

operatively (SD) was 5.2 4.3 (range, 0.021.0).Details of descriptive statistics and nonparametric

tests are shown inTable 8.

The only significant preoperative indicator for se-

vere postoperative pain was antibiotic prophylaxis

(Table 9): patients who received no antibiotic medi-

cation were found to have a higher risk for analgesic

consumption than those who received prophylaxis

(OR 2.20; P .005).

Two operative variables were found to be an

indicator for postoperative pain. When surgery was

perceived as being extremely difficult and a trape-

zoidal flap was raised, the patients had approxi-mately 3 times the odds of feeling severe postoper-

ative pain.

Table 4. RISK FACTORS FOR SEVERE DISCOMFORT (INDEPENDENT VARIABLES VERSUS FULL P OSSESCALE)

Independent Variables CategoryTotalNo.

PoSSe 0No.

PoSSe 1No. Odds Ratio CI 95% PValue

Gender M 120 73 47 1.00 1.183.60 .01F 135 65 70 2.07

Tobacco use No 179 102 77 1.00 1.023.40 .04

Yes 76 36 40 1.86Antibiotic prophylaxis Yes 119 75 44 1.00 1.213.45 .007

No 136 63 73 2.05Ramus relationship/

space availableClass I (sufficient) 9 7 2 1.00 0.4211.19 .34Class II (reduced) 217 121 96 2.18 1.0437.47 .04Class III (none) 29 10 19 6.24

NOTE. Logistic regression analysis: backward selection (P-to-remove: 0.1); goodness of fit: Pearson 2 test 186.50 (P .28). Odds ratio, 95%confidence intervals (CI) and Pvalues.


Table 5. RISK FACTORS FOR SEVERE DISCOMFORT (INDEPENDENT VARIABLES VS EACH P OSSESUBSCALE-GENDER)

PoSSe Subscales Category TotalNo.

PoSSe 0No.


Eating M 120 71 49 1.00F 135 63 72 2.40 1.374.20 .002

Speech M 120 74 46 1.00

F 135 66 69 2.02 1.183.45 .01Sensation M 120 85 35 NSF 135 93 42

Appearance M 120 65 55 1.00F 135 60 75 2.52 1.404.55 .002

Pain M 120 63 57 NSF 135 65 70

Sickness M 120 109 11 1.00F 135 83 52 6.20 3.0512.63 .000

Interference with daily activities M 120 68 52 1.00F 135 52 83 2.08 1.263.44 .004

NOTE. The table shows the gender-related odds ratio.Abbreviation: NS, the independent variable was not a statistically significant predictor of severe discomfort.




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Table 6. DESCRIPTIVE STATISTICS AND LEVELS OF SIGNIFICANCE (INDEPENDENT VARIABLES VS TRISMUS)


Dependent Variable Trismus (Differencein Mouth Opening in mm)

Kruskal-WallisRank Test

Mann-WhitneyUTest

Range (min) Range (max) Mean Median PValue PValue

Age (yrs)22 0.0 35.0 6.5 5.0 .0022329 0.0 35.0 9.0 7.029 0.0 36.0 10.6 8.0

GenderM 0.0 36.0 8.8 5.5 .40F 0.0 31.0 8.9 7.0





Number of rootsMultiple 0.0 36.0 9.3 7.0 .53Singular 0.0 31.0 8.1 6.0Incomplete 0.0 24.0 10.7 9.5


Mesioangular 0.0 36.0 8.7 6.0Depth

Level A (high) 0.0 25.0 5.9 5.0 .02Level B (medium) 0.0 36.0 9.7 7.0Level C (deep) 0.0 30.0 8.7 7.0


Surgeon1 0.0 36.0 6.7 4.5 .042 0.0 35.0 9.4 7.03 0.0 35.0 9.4 7.0







GROSSI ET AL 907


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VALIDATION OF THE POSSESCALE

The patients score on the PoSSe scale had signif-icant positive correlations with both differences inmouth opening (r 0.54) and total analgesic con-sumption (r 0.41) (Table 10). Correlations be-

tween the 7 PoSSe subscales and the 2 clinical

dependent variables are shown in Table 10. Thetotal analgesic consumption consistently gavestronger correlations with the pain subscale thanthe other (r 0.60). Similarly, differences in mouthopening strongly correlated with the eating sub-scale (r 0.53). Table 11 shows the correlationsbetween the subscale scores and the overall PoSSescore.

Figures 1through4 show the impact of gender onoutcome variables when such independent variablesinteract with other risk factors.

Table 12provides an overview of the risk factors fora severe discomfort found in this study. The antibioticprophylaxis was the only variable found statistically sig-nificant in all 3 regression logistic models of this study.

DiscussionMuch has been written about the relationships be-

tween the postoperative morbidity after surgical re-moval of lower third molars and preoperative riskfactors. However, little has been published on thepatients perceptions on quality of life after this op-eration. Moreover, most of these studies have testedthe individual variables isolated without adjusting for

the other potential risk indicators, several reportingonly descriptive data, making interpretation difficultbecause of inadequate analyses.

Table 6. (Contd)


Dependent Variable Trismus (Differencein Mouth Opening in mm)


Mann-WhitneyUTest

Range (min) Range (max) Mean Median PValue PValue


Total 0.0 36.0 8.9 6.0


Table 7. RISK FACTORS FOR SEVERE TRISMUS

Independent Variables CategoryTotalNo.

PoSSe 0No.


Age (yrs) 22 63 47 16 1.002329 117 70 47 2.93 1.316.56 .00929 75 39 36 3.23 1.387.58 .007

Gender M 120 79 41 1.00F 135 77 58 3.04 1.555.96 .001

Tobacco use No 179 115 64 1.00Yes 76 41 35 2.14 1.094.22 .02

Antibiotic prophylaxis Yes 119 85 34 1.00No 136 71 65 3.11 1.675.78 .000

Depth Level A (high) 43 35 8 1.00Level B (medium) 166 93 73 3.15 1.228.14 .01Level C (deep) 46 28 18 2.45 0.787.64 .12

Ramus relationship/spaceavailable

Class I (sufficient) 9 8 1 1.00Class II (reduced) 217 138 79 1.48 0.1514.04 .72Class III (none) 29 10 19 6.52 0.5971.88 .12

Surgeon 1 50 39 11 1.002 124 71 53 3.53 1.468.51 .0053 81 46 35 3.77 1.489.61 .005

Bone removal No 55 45 10 1.00Yes 200 111 89 3.95 1.669.41 .002



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Table 8. DESCRIPTIVE STATISTICS AND LEVELS OF SIGNIFICANCE (INDEPENDENT VARIABLES VS PAIN)


Dependent Variable-Pain (No. ofPainkillers Taken)


Mann-WhitneyUTest

Range (min) Range ( max) Mean Median PValue PValue

Age (yrs)22 0.0 21.0 4.0 2.0 .012329 0.0 18.0 5.5 4.029 0.0 17.0 5.7 5.0

GenderM 0.0 21.0 5.5 4.0 .21F 0.0 17.0 4.9 4.0





No. of rootsMultiple 0.0 21.0 5.2 4.0 .55Singular 0.0 16.0 5.1 3.0Incomplete 2.0 9.0 6.5 7.5


Mesioangular 0.0 21.0 5.4 3.5Depth

Level A (high) 0.0 13.0 4.6 3.0 .75Level B (medium) 0.0 21.0 5.3 4.0Level C (deep) 0.0 18.0 5.4 4.0


Surgeon1 0.0 11.0 3.9 3.0 .0022 0.0 21.0 6.1 5.03 0.0 14.0 4.6 3.0







GROSSI ET AL 909


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The following describes the outcomes of the studyand how our findings might influence the outcome ofpreviously published studies on risk factors for com-plications after third molar surgery.

PREOPERATIVE RISK FACTORS

Age

Removal of impacted third molar should not be

considered the best model for studying the age-re-lated differences because such operation is usuallycarried out on teenagers and young adults. However,it is commonly thought that older patients are atgreater risk for complications after third molar sur-gery.3,15,16

In our study, the patients age was found to be arisk factor only for severe trismus; that is, patientsaged 22.0 years were found to have a lower risk

than older patients.

Recently, Benediktsdttir et al17 studied the riskindicators for postoperative complications after re-moval of 388 mandibular third molars: older age (23

years) was found to increase the risk of an extendedoperation time (10 minutes), but operation time

itself was not found to be a risk indicator for postop-

erative complications. In the present study, after ad-

justment for other risk factors, no significant associa-

tion was found between age and the PoSSe score or

total painkillers consumption. This means that older

patients are at greater risk of severe trismus after third

molar surgery, but younger patients have the same

odds of perceiving severe discomfort and pain. If

other similar studies confirm these data, it will likely

be wrong to advocate the early prophylactic removal

of the lower third molar claiming lower risk of post-

operative discomfort.

Gender

There is general agreement that women and men

perceive and respond differently to pain stimuli.18-20

Moreover, biologic differences exist between men

and women that can result in differences in responses

to drugs.21-26

The most common finding after removal of third

molar is that women reported more postsurgical pain

that men.11,12,14,17 In contrast, Capuzzi et al,27 in 146

patients having third molar surgery, reported that

Table 8. (Contd)


Dependent Variable-Pain (No. ofPainkillers Taken)


Mann-WhitneyUTest

Range (min) Range ( max) Mean Median PValue PValue


Total 0.0 21.0 5.2 4.0


Table 9. RISK FACTORS FOR SEVERE PAIN (NUMBER OF PAINKILLERS TAKEN)

Independent Variables Category

Pain (No. of PainkillersTaken)

Odds Ratio CI 95% PValueTotal

No.

PoSSe 0

No.

PoSSe 1

No.

Antibiotic prophylaxis Yes 119 80 39 1.00No 136 74 62 2.20 1.273.81 .005

Flap design Envelope flap 59 35 24 1.87 0.695.09 .21Vestibular triangular flap 48 35 13 1.00Vestibular trapezoidal flap 148 84 64 2.87 1.326.24 .007

Extraction difficulty Elevator/forceps alone 49 27 22 2.42 0.866.82 .09Bone removal/tooth sectioning 46 32 14 1.00Bone removal tooth/root

sectioning129 82 47 1.34 0.632.85 .44

Extremely difficult 31 13 18 3.32 1.248.91 .01





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there was no gender-related differences in regard tothe number of analgesic tablets taken.

In the present study, gender was not found to be arisk factor for objectively measured pain (total pain-killer consumption), or for subjectively measured

pain (pain subscale score).On the other hand, among our cohort of patients,

females had more than 3 times higher risk for severe

trismus compared with males, and thesefindings arein agreement with previous studies.11,12

For gender differences in symptom reporting, thedata show that females had twice the odds of males ofperceiving a severe postoperative discomfort (fullPoSSe score). Especially, except forpain and sensa-tion subscales that have not shown differences to begender-related, females were found to complain morethan males about sickness (OR 6.2; P .000),appearance (OR 2.52; P .002), eating (OR 2.40; P 0.002), speech (OR 2.0; P .01) andinterference with daily activities (OR 2.0; P .004) (Table 5).

It can be proposed that the strong gender-relateddifference found for sicknessmay be attributable to

the type of painkiller prescribed in our study, acodeine-combined drug. In fact, it was shown that

women had 60% higher risk of nausea and vomitingthan men when taking opioid agonists, althoughefficacy did not differ between the 2 groups.28

Finally, it seems that some risk factors increasegender differences. Smoking appears to increasethe PoSSe score and the total painkiller consump-tion in females much more than in males (Figs 1and

4). Women are less likely than men to benefit from

antibiotic prophylaxis (Fig 2), and are more likely

than men to perceive severe discomfort when athird molar with no space available was removed(Fig 3).

It is commonly believed that situational and psy-chological factors can play a major role in symptomperception and that the gender differences cannot

simply be attributed to a greater physical morbidityin women. Contrary to popular belief, recent studiesindicate that when an actual illness or disease is present,

however minor and transient, men and women areeither equally likely to report related symptoms, ormen report more severe symptoms.29

However, being male or female is an importantfundamental variable that should be considered whendesigning and analyzing the results of studies in allareas and at all levels of biomedical and health-relatedresearch. Therefore, subjects who have lower thirdmolars extracted should not be viewed as a uniform

population when postoperative discomfort is evalu-ated, but should be stratified by gender.

Such data in relation to gender differences mayhelp surgeons to counsel female patients about recov-ery after third molar surgery and will enhance theinformed consent procedures.

Tobacco Use

Smoking has been shown to have a deleteriouseffect on the oral cavity and has been associated withpostoperative complications after oral surgery.30-35

In the present study, patients who smoke werefound to have a higher risk for perceiving more severe

postoperative discomfort (OR 1.86; P .04) andtrismus (OR 2.14; P .02).

It was shown that women who smoke are morelikely to develop diseases than men.36 This is consis-tent with our finding that smoking appears to en-hance gender differences in PoSSe score (Fig 1).

Interestingly, it has been reported that nicotineincreases the pain threshold and tolerance rating of

Table 11. SPEARMANS CORRELATION COEFFICIENTTO ASSESS CORRELATION BETWEEN THE POSSE

SCALE AND SUBSCALES

Subscale Full PoSSe

Eating 0.83*Speech 0.65*Sensation 0.37*Appearance 0.54*Pain 0.67*Sickness 0.35*Interference with daily activities 0.71*

*P .01.


Table 10. VALIDITY TESTING, SPEARMANSCORRELATION COEFFICIENT TO ASSESSCORRELATION BETWEEN THE POSSESCALE, POSSESUBSCALES, AND THE TWO CLINICAL DEPENDENTVARIABLES (TRISMUS AND PAIN)

Subjective DependentVariable

Objective DependentVariable

Pain (No. of Painkillers

Taken) Trismus

Full PoSSe 0.41** 0.54**Eating 0.26** 0.53**Speech 0.21** 0.34**Sensation 0.11 0.10Appearance 0.13* 0.41**Pain 0.60** 0.30**Sickness 0.05 0.18**Interference with daily

activities 0.29** 0.38**

*P .05.**P .01.


GROSSI ET AL 911


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men, but has no effect on the pain rating of women.37

These findings can be an explanation of why smokersas a whole in this study were not found at higher riskfor pain and why female smokers consumed morepainkillers than male smokers (Fig 4).

Oral Contraceptive Use

Numerous studies reported increased complica-tions among females associated with oral contracep-tive use.35,38-41 However, most of these studies have

not been optimally designed or analyzed to removethe effects of various known confounders. This study

fails to confirm the hypothesis that oral contraceptiveuse is a risk factor for severe postoperative discom-fort, which is consistent with other studies.16,33,42

However, data on the menstrual cycle of the womenwere not gathered. Therefore, these findings shouldbe interpreted with caution and further studies areneeded to consider the endocrine status of subjects inanalyses.

Antibiotic Prophylaxis

The routine use of systemic preoperative and/orpostoperative antibacterial given prophylactically is

FIGURE 1. Relationship between gender*tobacco use versus full PoSSe score.

Grossi et al. Assessing Discomfort AfterThird Molar Surgery. J Oral Maxillofac Surg2007.

FIGURE 2. Relationship between gender*antibiotic prophylaxis versus full PoSSe score.




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highly disputed and by many considered to be con-troversial because of the development of resistant

bacterial strains and possible systemic side effects,such as hypersensitivity and unnecessary destructionof host flora.43-45

Several studies have shown that postoperative oralprophylactic antibiotic treatment after the removal oflower third molars does not contribute to a better

wound healing, less pain, or increased mouth open-

ing.27,46,47 In contrast, Delilbasi et al48 reported someevidence of the benefit of postoperative antibiotic for

the prevention of alveolar osteitis. However, surgicalprinciples dictate that if preventive antibiotics are

given to improve recovery, the drug should be admin-istered just before surgery at a sufficient dosage toensure adequate blood and tissue levels, and discontin-ued after surgery.44,49,50 Nevertheless, Sekhar et al51

failed to show any advantage in the routine preoper-ative or postoperative use of metronidazole duringremoval of third molars.

In this study, preoperative antibiotic prophylaxiswas found to be the only independent variable statis-

FIGURE 3. Relationship between gender*ramus relationship/space available versus fullPoSSe score.


FIGURE 4. Relationship between gender*tobacco use versus number of painkillers taken.


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tically significant (P .01) versus all outcome vari-ables studied (Table 12).

Of note, women looked less likely than men tobenefit from antibiotic prophylaxis (Fig 2). This find-ing could be explained by the gender differences inpharmacokinetics and pharmacodynamics.52 Aboveall, gender differences in hepatic enzymes seem toplay a major role in determining pharmacokinetic

variability by gender.22,52,53 Amoxicillin/clavulanicacid was used as a prophylactic antibiotic treatment.

It was reported that erythromycin is cleared morerapidly in women than men,52 and there may be a

common metabolic pathway forboth amoxicillin/cla-vulanic acid and erythromycin.54 Moreover, it wasshown that men are much more frequently affectedby amoxicillin/clavulanic acid-induced hepatitis than

women (male to female ratio, 4:1) and it is likely thatclavulanic acid is responsible for the hepatotoxicity.54

It can be hypothesized that when clavulanic acid was

given to females, because of the faster hepatic metabo-lism, it cannot provide enough anti--lactamase activitycapable to enhance the activity of amoxicillin. However,these findings have not been confirmed in the literatureand further studies are needed.

Indication for RemovalIt has been suggested that the presence of symp-

toms at the time of mandibular third molar removalmust be consideredto be a risk factor for postopera-tive complications55 or delay of wound healing.12 Inthe present study, we fail to confirm this hypothesis,perhaps because all patients in this study were free ofcaries, extensive periodontal disease, pain, or other

inflammatory symptoms at the time of operation.

Radiographic Findings

Classically, the assessment of difficulty of extrac-tion has been based on angulation, depth of impac-

tion, ramus, and occlusal positions. Bui et al16

re-ported that mesioangular impactions were associated

with a higher risk forpostoperative complications;whereas Yuasa et al56 found that depth and ramusrelationship/space available were associated with dif-ficulty in extraction. We found that deeply impactedmolar and insufficient space available in relation tothe ramus were risk factors for severe postoperativediscomfort.

Different than operative variables (ie, operative

time and extraction difficulty), information gatheredfrom a panoramic radiograph can help the surgeon

plan the surgery and inform the patient of the likeli-hood of postoperative complications.

Operative Risk Factors

Many studies have emphasized that operative fac-tors were strong indicators for postoperative compli-cations.

From the patients perspective, in this study noneof the operative variables were found to be risk fac-tors for severe discomfort (PoSSe score). If these dataare confirmed, the clinician could counsel a patientbefore surgery about their outcome, with only a slight

chance that an event at surgery would drastically alter

what was advised presurgically.Flap Design

There are very few specific data available from the

literature regarding postoperative flap-related discom-fort. In this study, the triangular flap design was asso-ciated with those consuming the least painkillers.

When a trapezoidal flap was raised the patients hadapproximately 3 times the odds of taking an above-average number of painkillers. Of note, although sur-geons in this study used an envelope flap technique

when the lower third molar surgery was expected tobe easy, when access was achieved with such a flap

Table 12. OVERVIEW OF POSSIBLE RISK FACTORS

Dependent Variable

Preoperative Independent Variable Operative Independent Variable

AGE

GENDER

TOBACCO

USE

ORALCONTRA

CEPTIVEUSE

ANTIBIOTICPROPHYLAXIS

INDICATIONF

ORREMOVAL

NUMBEROFR

OOTS

SPATIALRELATIONSHIP

DEPTH

RAMUSRELATIONSHIP

SURGEON

ASSISTANTSURGEON

FLAPDESIGN

BONEREMOVAL

EXTRACTION

DIFFICULTY

OPERATIONTIME

Trismus No. of painkillers taken Full PoSSe score

, Statistically significant predictor.




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patients had almost twice the odds of consuming

more painkillers than when a triangular flap was used.These findings are consistent with those from Jakseet al,57 who stated that the envelope flap has a nearly6 times higher risk of dehiscence during primary

wound healing than the triangular flap. These authorshypothesized that soft tissue tensions resulting from

postoperative hematoma and masticatory movementsmay induce a rupture of the wound margin during thefirst few postoperative days. This would be more

likely when envelope flap is raised because it is fixedanteriorly with intersulcular sutures.

Extraction Difficulty

It is commonly thought that there is a relationshipbetween operative trauma and the magnitude of post-operative pain, and that the amount of mucoperios-teum that has to be reflected and of bone that has tobe removed affect the severity of postoperative pain

and swelling.

55

Evaluating the odds of consumingpainkillers, data from the present study confirm thishypothesis (except for removal with elevator/forcepsalone, which had higher odds for severe pain than

bone removal/tooth root sectioning). It may be sug-gested that sometimes raising a small flap withoutbone removal and/or tooth/root sectioning is not agood idea, causing patients to suffer more severe painpresumably because of the excessive soft tissue dam-age and delayed wound healing.

However, extraction difficulty was not found statis-tically significant versus patients perceptions of dis-comfort (PoSSe score). It is possible that patients

assessed postoperative third molar pain as better or asexpected. Another explanation may be that pain was

well controlled by painkillers.

Surgeon

It has been previously suggested that surgical ex-perience is closelyrelated to the postoperative com-plication rate,27,55 although other studies have failedto show any relationship.17,58 The skill of the surgeonhas been identified as a risk factor for severe trismusbut not for severe pain or for higher PoSSe score. Apossible explanation for these findings could be that

all surgeons in this study had more than 5 yearsdentoalveolar training and used the same surgical ap-proach, in the same operating room, and under sim-ilar conditions.

Operation Time

Several studies have stated that the length of theoperation could be used as a proxy variable for ex-traction difficulty.59-61 Other studies reported that pa-tients whose surgery time was 30 minutes or longerhad a prolonged recovery.11,12 Consistent with previ-ous studies, our results fail to confirm the hypothesis

that operation time is a risk factor for severe postop-

erative discomfort.17,46 These findings may be attrib-

utable to the fact that the variation was not large in thisstudy, that is, the mean operating time was 24.4 15.9minutes. Interestingly, the surgeon whose patientshad less postoperative discomfort spent more time inperforming the operations (mean operating time 30.7 vs 23.6 and 21.8 minutes).

It could be wrong to assume that operating time iscorrelated with postoperative discomfort, transpos-ing such concept from general surgery to minor oral

surgery, where operating time is rarely longer than 1hour.

Validation of the PoSSe Scale

In a recent study, Ruta et al13 developed a postop-erative symptom severity (PoSSe) scale specific toextractions of third molars and assessed its validity tomeasure the impact of those symptoms on patientsperceived quality of life. In our study, the clinical

validity of the PoSSe scale was provided by its ability

to discriminate between different groups of patientsand to correlate with trismus and pain objectivelymeasured. The pilot study of Ruta et al13 showed ahighly significant association between the number ofpainkiller tablets taken and the PoSSe score. In thisstudy, we found that the PoSSe score was stronglycorrelated with both trismus (r 0.54) and numberof painkillers taken (r 0.41). Consistently, trismusgave higher correlations with theeatingsubscale (r

0.53) and the number of painkillers taken withpainsubscale (r 0.60). Finally, eating (r 0.83) andinterference with daily activities(r 0.71) subscales

gave higher correlations with the full PoSSe score.According to Ogden et al,7 patients participating inthis study felt that surgery exerted its impact on theirquality of life primarily by reducing their ability to eatand interference with daily life. These findings couldhave important implications for the surgeon when

attending to postoperative problems and when ob-taining informed consent.

Acknowledgment

The authors thank Dr Dario Consonni for his advice and assis-tance regarding the statistical analyses.

References1. Valmaseda-Castelln E, Berini-Ayts L, Gay-Escoda C: Inferior

alveolar nerve damage after lower third molar surgical extrac-tion: A prospective study of 1117 surgical extractions. OralSurg Oral Med Oral Pathol Oral Radiol Endod 92:377, 2001

2. Renton T, McGurk M: Evaluation of factors predictive of lingualnerve injury in third molar surgery. Br J Oral Maxillofac Surg39:423, 2001

3. Goldberg MH, Nemarich AN, Marco WP: Complications aftermandibular third molar surgery: A statistical analysis of 500consecutive procedures in private practice. J Am Dent Assoc111:277, 1985

4. Indresano AT, Haug RH, Hoffman MJ: The third molar as acause of deep space infections. J Oral Maxillofac Surg 50:33,1992

GROSSI ET AL 915


16/17

5. Savin J, Ogden GR: Third molar surgeryA preliminary reporton aspects affecting quality of life in the early postoperativeperiod. Br J Oral Maxillofac Surg 35:246, 1997

6. McGrath C, Comfort MB, Lo EC, et al: Changes in life qualityfollowing third molar surgeryThe immediate postoperativeperiod. Br Dent J 194:265, 2003

7. Ogden GR, Bissias E, Ruta DA, et al: Quality of life followingthird molar removal: A patient versus professional perspective.Br Dent J 185:407, 1998

8. Cunningham SJ, Hunt NP, Feinmann C: Perceptions of out-come following orthognathic surgery. Br J Oral Maxillofac Surg34:210, 1996

9. McGrath C, Comfort MB, Lo EC, et al: Patient-centered out-come measures in oral surgery: validity and sensitivity. Br J OralMaxillofac Surg 21:43, 2003

10. Shugars DA, Benson K, White RP Jr, et al: Developing a mea-sure of patient perceptions of short-term outcomes of thirdmolar surgery. J Oral Maxillofac Surg 54:1402, 1996

11. Conrad SM, Blakey GH, Shugars DA, et al: Patients perceptionof recovery after third molar surgery. J Oral Maxillofac Surg57:1288, 1999

12. Phillips C, White RP, Shugars DA, et al: Risk factors associatedwith prolonged recovery and delayed healing after third molarsurgery. J Oral Maxillofac Surg 61:1436, 2003

13. Ruta DA, Bissias E, Ogston S, et al: Assessing health outcomesafter extraction of third molars: The postoperative symptomseverity (PoSSe) scale. Br J Oral Maxillofac Surg 38:480, 2000

14. Fisher SE, Frame JW, Route PGJ: Factors affecting the onset andseverity of pain following the surgical removal of unilateralimpacted mandibular third molar teeth. Br Dent J 164:351,1988

15. Bruce RA, Frederickson GC, Small G: Age of patients andmorbidity associated with mandibular third molar surgery.

J Am Dent Assoc 101:240, 198016. Bui CH, Seldin EB, Dodson B: Types, frequencies, and risk

factors for complications after third molar extraction. J OralMaxillofac Surg 61:1379, 2003

17. Benediktsdttir IS, Wenzel A, Petersen JK et al: Mandibularthird molar removal: Risk indicators for extended operationtime, postoperative pain, and complications. Oral Surg OralMed Oral Pathol Oral Radiol Oral Endod 97:438, 2004

18. Feine JS, Bushnell MC, Miron D, et al: Sex differences in theperception of noxious heat stimuli. Pain 44:255, 1991

19. Berkley KJ: Sex differences in pain. Behav Brain Sci 20:371,1997

20. Wizeman TM, Pardue ML: Exploring the Biological Contribu-tions to Human Health: Does Sex Matter? Washington, DC,National Academy Press, 2001

21. Walker JS, Carmody JJ: Experimental pain in healthy humansubjects: Gender differences in nociception and in response toibuprofen. Anesth Analg 86:1257, 1998

22. Harris RZ, Benet LZ, Schwartz JB: Gender effects in pharmaco-kinetics and pharmacodynamics. Drugs 50:222, 1995

23. Tanaka E: Gender-related differences in pharmacokinetics andtheir clinical significance. J Clin Pharm Ther 24:339, 1999

24. Ingelman-Sundberg M, Oscarson M, McLellan RA: Polymor-

phisms human cytochrome P450 enzymes: An opportunity forindividualized drug treatment. Trends Pharmacol Sci 20:342,1999

25. Craft RM: Sex differences in opioid analgesia: From mouse toman. Clin J Pain 19:175, 2003

26. Bock K, Schrenk D, Forster A, et al: The influence of environ-mental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine, andparacetamol as probes. Pharmacogenetics 4:209, 1994

27. Capuzzi P, Montebugnoli L, Vaccaro MA: Extraction of im-pacted third molars. A longitudinal prospective study on fac-tors that affect postoperative recovery. Oral Surg Oral Med OralPathol 77:341, 1994

28. Cepeda MS, Farrar JT, Baumgarten M, et al: Side effects ofopioids during short-term administration: Effect of age, gender,and race. Clin Pharmacol Ther 74:102, 2003

29. Gijsbers van Wijk CMT, Kolk AM: Sex differences in physicalsymptoms: The contribution of symptom perception theory.Soc Sci Med 45:231, 1997

30. Bergstrom J, Preber H: Tobacco use as a risk factor. J Periodon-tol 65:545, 1994

31. Jones JK, Triplett RG: The relationship of cigarette smoking toimpaired intraoral wound healing: A review of evidence andimplications for patient care. J Oral Maxillofac Surg 50:237, 1992

32. Grossi SG, Zambon J, Machtei EE, et al: Effects of smoking and

smoking cessation on healing after mechanical periodontaltherapy. J Am Dent Assoc 128:599, 1997

33. Larsen PE: Alveolar osteitis after surgical removal of impactedmandibular third molars. Identification of the patient at risk.Oral Surg Oral Med Oral Pathol 73:393, 1992

34. Al-Belasy FA: The relationship of Shisha (water pipe) smokingto postextraction dry socket. J Oral Maxillofac Surg 62:10, 2004

35. Sweet JB, Butler DP: Increased incidence of postoperativelocalized osteitis in mandibular third molar surgery associated

with patients using oral contraceptives. Am J Obstet Gynecol127:518, 1977

36. Bolego C, Poli A, Paoletti R: Smoking and gender. CardiovascRes 53:568, 2002

37. Jamner LD, Girdler SS, Shapiro D, et al: Pain inhibition, nico-tine, and gender. Exp Clin Psychopharmacol 6:96, 1998

38. Garcia AG, Grana PM, Sampedro FG, et al: Oral contraceptive and

complication in third molar surgery. Br Dent J 194:453, 200339. Chapnick P, Diamond L: A review of dry socket: a double-blindstudy on the effectiveness of clindamycin in reducing theincidence of dry socket. J Can Dent Assoc 58:43, 1992

40. Cohen ME, Simecek JW: Effects of gender-related factors on theincidence of localized alveolar osteitis. Oral Med Oral PatholOral Radiol Endod 79:416, 1995

41. Catellani JE, Harvey S, Erickson SH, et al: Effect of oral contra-ceptive cycle on dry socket (localized alveolar osteitis). J AmDent Assoc 101:777, 1980

42. Heasman PA, Jacobs DJ: A clinical investigation into the inci-dence of dry socket. Br J Oral Maxillofac Surg 22:115, 1984

43. Zeitler DL: Prophylactic antibiotics for third molar surgery: Adissenting opinion. J Oral Maxillofac Surg 53:61, 1995

44. Piecuch JF, Arzadon J, Lieblich SE: Prophylactic antibiotics forthird molar surgery: A supportive opinion. J Oral MaxillofacSurg 53:53, 1995

45. Worrall SF: Antibiotic prescribing in third molar surgery [let-ter]. Br J Oral Maxillofac Surg 36:74, 1998

46. Monaco G, Staffolani C, Gatto MR, et al: Antibiotic therapy inimpacted third molar surgery. Eur J Sci 107:437, 1999

47. Poeschl PW, Eckel D, Poeschl E: Postoperative prophylacticantibiotic treatment in third molar surgeryA necessity? J OralMaxillofac Surg 62:3, 2004

48. Delilbasi C, Saracoglu U, Keskin A: Effects of 0.2% chlorhexi-dine gluconate and amoxicillin plus clavulanic acid on theprevention of alveolar osteitis following mandibular third mo-lar extractions. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 94:301, 2002

49. Stone HH, Hooper CA, Kolb LD, et al: Antibiotic prophylaxis ingastric, biliary and colonic surgery. Ann Surg 184:443, 1976

50. Classen DC, Evans RS, Pestotnik SL, et al: The timing of pro-phylactic administration of antibiotics and the risk of surgical

wound-infection. N Engl J Med 326:281, 199251. Sekhar CH, Narayanan V, Baig MF: Role of antimicrobials in

third molar surgery: Prospective, double blind, randomized,placebo-controlled clinical study. Br J Oral Maxillofac Surg39:134, 2001

52. Gandhi M, Aweeka F, Greenblatt RM, et al: Sex differences inpharmacokinetics and pharmacodynamics. Annu Rev PharmacolToxicol 44:499, 2004

53. Hersh EV, Moore PA: Drug interactions in dentistry. The impor-tance of knowing your CYPs. J Am Dent Assoc 135:298, 2004

54. Gresser U: Amoxicillin-clavulanic acid therapy may be associ-ated with severe side effects-review of the literature. Eur J MedRes 6:139, 2001

55. De Boer MPJ, Raghoebar GM, Stegenga B, et al: Complicationafter mandibular third molar extraction. Quintessence Int 26:779, 1995



17/17

56. Yuasa H, Kawai T, Sugiura M: Classification of surgical difficultyin extracting third molars. Br J Oral Maxillofac Surg 40:26, 2002

57. Jakse N, Bankaoglu V, Wimmer G, et al: Primary wound healingafter lower third molar surgery: Evaluation of 2 different flapdesigns. Oral Surg Oral Med Oral Pathol 93:7, 2002

58. Oginni FO, Fatusi OA, Alagbe AO: A clinical evaluation of drysocket in a Nigerian teaching hospital. J Oral Maxillofac Surg61:871, 2003

59. Susarla SM, Dodson TB: Risk factors for third molar extractiondifficulty. J Oral Maxillofac Surg 62:1363, 2004

60. Santamaria J, Arteagoitia I: Radiologic variables of clinical sig-nificance in the extraction of impacted mandibular third mo-lars. Oral Surg Oral Med Oral Pathol 84:469, 1997

61. Renton T, Smeeton N, McGurk M: Factors predictive of diffi-culty of mandibular third molar surgery. Br J Oral MaxillofacSurg 190:607:10, 2001

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