The sequelae of third molar surgery include pain, edema, trismus, infection, dry socket etc. Various drugs are used to minimize or eliminate these outcomes. The objective is to make the surgical procedure as pleasant as possible to the patient without causing serious side effects.
Drugs can be administered prophylactically or empirically. A drug that is administered before a surgical procedure is referred to as prophylactic therapy, while that is administered after the procedure is referred to as empirical therapy
One of the primary goals of the surgeon in performing any surgical procedure is to prevent postoperative infection as a result of surgery. To achieve this goal, prophylactic antibiotics are necessary in some surgical procedures.
In general the rationale for the use of antibiotic is based on wound classification. The following table on the next pages hows the classification of various types of wounds and the indication for antibiotic prophylaxis.
Surgery for the removal of the impacted third molars fits into the category of clean/contaminated surgery. The incidence of infection is usually between 2% and 3%. It is difficult and probably impossible to reduce infection rates below 3% with the use of prophylactic antibiotics. Therefore, it is unnecessary to use prophylactic antibiotics in third molar surgery to prevent postoperative infections in the normal healthy patient. Although the literature contains many papers that discuss the use of prophylactic perioperative antibiotics, there is essentially no report of their usefulness in prevention of infection following third molar surgery.
Based on various reports it seems that the risk of postoperative infection after third molar surgery increases in the presence of following factors:
1. Increased time of surgery
2. Decreased operator experience
3. Increased surgical complexity
4. Higher incidence following mandibular third molar removal
5. Age-patients older than 34 years
The use of prophylactic antibiotics in third molar surgery does, in fact, reduce the incidence of dry socket. Although systemic antibiotics are effective in the reduction of postoperative dry socket, they are no more effective than local non systemic measures like copious irrigation, preoperative rinses with chlorhexidine, and placement of antibiotics in the extraction socket. The incidence of antibiotic related complications such as allergy, bacterial resistance, gastrointestinal (GI) side effects and secondary infections are not outweighed by the benefits. Therefore the routine use of perioperative systemic antibiotic administration does not seem to be valid.
The results of study by Poeschl et al (2004)1 showed that specific postoperative oral prophylactic antibiotic treatment after the removal of lower third molars does not contribute to a better wound healing, less pain, or increased mouth opening and could not prevent inflammatory problems after surgery. And therefore is not recommended for routine use. This finding is supported by the findings of Hill (2005).2
However, in a recent study by Halpern et al (2007)3 has shown that following third molar removal the use of intravenous antibiotics (penicillin and clindamycin in those allergic to penicillin) administered prophylactically decreased the frequency of surgical site infection. The authors cannot comment on the efficacy of intravenous antibiotics in comparison to other antibacterial treatment regimens, e.g. chlorhexidine mouth rinse or intra socket antibiotics.
The comparison of various studies poses a tremendous challenge because of the variability in parameters and the methods used for each study.
Even though surgery of impacted third molar do not commonly result in serious nosocomial infections, efforts to prevent prolonged recovery periods caused by delayed wound healing and wound infection are beneficial economically. Considering the cost of antibiotic therapy compared to hospital stay/absenting from work, antibiotics should be administered to all patients who have increased susceptibility to infection.
Patients who undergo surgical removal of third molar are generally healthy and are not likely to develop postoperative infection. Factors that increase the risk of postoperative infection in any surgical patients include diabetes, cirrhosis, end-stage renal disease, corticosteroid therapy, old age, obesity, malnutrition, massive trans- fusion, preoperative comorbid disease and American Society of Anesthesiologists (ASA) patient classification III, IV and V.
Use of prophylactic or empiric antibiotic therapy is recommended for patients with comorbid diseases. It is also well accepted that patients who are afflicted with any systemic disease that compromises the immune defense system against bacterial infection (e.g. neutropenia, leukopenia, splenectomy, leukemia, myeloproliferative diseases) are candidates for antibiotic therapy before and after third molar surgery. There is also no controversy regarding administration of preoperative antibiotic therapy in the management of fascial space infection or dentoalveolar abscess associated with impacted third molars. Similarly antibiotics are indicated for patients susceptible to subacute bacterial endocarditis and also for prosthetic joint replacement cases.
Early in the antibiotic era, prophylactic antibiotic therapy was thought to be associated with higher rates of infection and resistance. This belief was disproved in a study conducted by Bruke in 1961. This study also showed that the timing of administration of prophylactic antibiotics has great significance. The timing of a surgical incision should correspond with the peak systemic concentration of the antibiotic administered. It has been determined that the ideal timing for prophylactic antibiotic therapy is 30 minutes to two hours before surgery. This is followed by additional coverage extending for one to two half-lives of the prescribed antibiotic for the length of the operation. Moreover, the dose of the antibiotic should be twice the therapeutic dose. In the absence of infection antibiotics should not be continued beyond the operative day
Proper administration of antibiotic prophylaxis requires evaluation of various factors such as the type of surgery performed, organisms involved, choice of antibiotic, its dosage and administration. Identification of the organism involved in infection at third molar sites has been difficult. Studies have shown a higher prevalence of anaerobic organisms even when the periodontal probing depths were normal. However studies have shown that aerobic streptococci were the most commonly found organism present in infected third molar wounds. This variety in the microbial population causes difficulty in selecting the appropriate antibiotic.
In the event that the operator is planning to give an antibiotic the following principles should be considered before prescribing antibiotics:
1. The surgical procedure should harbor a significant risk for infection, for example:
• Long procedure (> 30 minutes) or difficult surgery involving significant tissue trauma.
• Where there is existing infection in and around the surgical site.
2. Administration of the antibiotic must be immediately prior to or within 3 hours after the start of surgery:
• The ability of systemic antibiotics to prevent the development of a primary bacterial lesion is confined to the first 3 hours after inoculation of the wound.
• Commencing prophylactic antibiotic cover the day before surgery only leads to the development of resistant organisms.
• Continuing antibiotics for days after surgery has not been shown to decrease the incidence of wound infection.
3. Prophylactic antibiotics should be given at twice the usual dose over the shortest effective time so as to minimize the potential side-effects of long term use (e.g. diarrhea) and to prevent the growth of resistant strains of bacteria.
4. There are many antibiotic prophylactic regimens currently used. The following are just a few that may be considered
• Amoxicillin 3 gm orally, 45 minutes before surgery under local anesthesia.
• Clindamycin 600 mg orally, 30 minutes before surgery under local anesthesia for patients allergic to penicillin.
• Benzyl Penicillin 600 mg IV/IM on induction for procedures under general anesthesia.
• Erythromycin lactobionate 500 mg IV on induction for surgery under general anesthesia for patients allergic to penicillin
The above dose may be followed with an additional oral dose 6 hours after the initial dose.
To conclude, an analysis of the current literature on the topic supports routinely prescribing and not prescribing antibiotics as part of the removal of asymptomatic impacted third molars, thus making it surgeon's preference. For patients with active infection and medically compromised patient who is more susceptible to infection, prophylactic antibiotics are indicated and should be administered one to two hours before the surgical procedure. The presence of anaerobic bacteria at the third molar area without the evidence of periodontal disease supports the use of prophylactic antibiotics in all cases of impacted mandibular third molar removal. A strong argument against the routine use of prophylactic antibiotics in third molar removal is the possibility of emergence of antibiotic resistant strains. However, till date this occurrence has not been documented in cases of third molar removal (Mehrabi et al, 2007).4
Use of Anti-inflammatory Drugs and Steroids
As a result of the trauma occurring during surgical extraction of third molars inflammatory response occurs resulting in edema, pain and trismus after the operation. Maximum edema after surgical extraction of third molars was found to occur between 48 to 72 hours (Peterson, 1998)5. This occurs because of the release of cytokines, prostaglandins, and histamine from leukocytes, endothelial cells and mast cells. The increase in osmotic pressure within injured tissues and leakage from capillaries are responsible for the expansion of tissues that occurs with edema. Corticosteroids have been shown to reduce edema following third molar surgery (Messer et al, 1975).6 Steroids act by interfering with capillary vasodilation, leukocyte migration, phagocytosis, cytokine production and prostaglandin inhibition. The inhibition of capillary vasodilation prevents entry of intravascular fluid into interstitial space. The leakage of fluid and leukocytes results in irritation of free nerve endings and this in turn cause release of pain mediators, including prostaglandin and substance perioperative corticoste- roids act to prevent inflammation and reduce pain at the site of insult. The anti-inflammatory action of steroids is dependent on the dose and increases as the plasma concentration in proximity to the surgical site reaches the therapeutic range.
The use of perioperative corticosteroids to minimize swelling, trismus and pain has gained wide acceptance in the practice of oral and maxillofacial surgery. However, the method of usage is extremely variable. The one which is most effective has yet to be clearly delineated.
The body's daily production of cortisol is 15 to 30 mg, which may increase up to 300 mg during a stressful event. The normal concentration of cortisol in a healthy patient is 13 µg/ dL. This may increase up to 50 - 73 µg/ dL in septic shock. The most widely used steroids are dexamethasone and methylprednisolone. Both of these are almost pure glucocorticoids with little mineralocorticoid effect. Also, these two appear to have the least depressing effect on leukocyte chemotaxis. Common dosages of dexa- methasone are 4 to 12 mg given IV at the time of surgery. Additional oral dosages of 4 to 8 mg. twice a day for the day of surgery and 2 days afterwards leads to the maximum relief of swelling, trismus and pain. Methylprednisolone is most commonly given IV 125 mg at the time of surgery followed by significantly lower doses, usually 40 mg 3 or 4 times daily taken orally for the day of surgery and for 2 days after surgery. It is important to note that a tapered dose of steroids after third molar surgery is prescribed not to compensate for adrenal suppression; but rather to correlate with the decline in surgical stress in the 72 hour postoperative period. The bioavailability of glucocorticoids after oral administration is remarkably high and may provide effects that parallel intravenous administration. Gastrointestinal side effects, however, are known to occur from oral intake. Steroids given orally three to four hours before surgery lessen gastrointestinal upset. In an outpatient environment, patient compliance may not always be optimal with regards to timing of intake. High dose, short-term steroid use is associated with minimal side effects. They are contraindicated in patients with gastric ulcer disease, active infection, active tuberculosis, acute glaucoma and certain type of psychosis. Relative contraindications include diabetes mellitus, hypertension, osteoporosis, peptic ulcer disease, infection, renal disease, Cushing's syndrome and diverticulitis. The adminis- tration of perioperative steroids may increase the incidence of dry socket after third molar surgery, but the data is lacking as to the precise degree of increase.
Recent work on the use of corticosteroids would suggest that these drugs are of great value in reducing postoperative sequelae after third molar surgery. Short- term steroid therapy is not associated with the development of adrenal crisis. However, there is no consensus of opinion regarding the ideal preparation and dosage to be used following surgery of impacted molar. Patients on long-term steroid therapy: Continuous daily administration of corticosteroids for a month results in suppression of adrenal glands and internal corticosteroid production. Such patients require a doubling of the steroid dose on the day of the surgery, followed by gradual tapering postoperatively back to the original daily dose. Adrenal insufficiency may occur up to one year after cessation of steroid therapy. Even if these patients have discontinued their steroid therapy for up to one year, a tapering dose of steroids may be required for surgery. Intraoperative adrenal insufficiency most commonly presents as hypotension that is resistant to fluid treatment but responds to steroid therapy. When adrenal insufficiency is suspected preoperatively, cortisol stimulation test can be performed. An initial cortisol level is obtained first. Adrenocorticotropic hormone is then injected and the cortisol level estimated in one hour. If the cortisol level does not increase, a diagnosis of primary adrenal insufficiency can be made.
The adverse effects of prolonged steroid adminis- tration are extensive. They include poor wound healing, hypertension, electrolyte abnormality, psychosis, euphoria, osteoporosis, hyperglycemia, central obesity, abdominal striae, thin skin, glaucoma, myopathy, amenorrhea, hirsutism, acne and adrenal insufficiency. Short term steroid therapy like that used following third molar surgery is not associated with the above side effects.
Combining Steroids and NSAIDs
Buyukkurt et al (2006)7 reported that the combination of a single dose of prednisolone and diclofenac is well-suited to the treatment of postoperative pain, trismus, and swelling after dental surgical procedures and should be used when extensive postoperative swelling of soft tissue is anticipated.
Schultze-Mosgau et al (1995)8 conducted a study to assess the efficacy of ibuprofen and methylprednisolone in the treatment of pain, swelling and trismus following the surgical extraction of impacted third molars. This regimen included 32 mg of methylprednisolone 12 hours before and after the procedure and 400 mg of ibuprofen three times per day on the day of the operation and for the first two postoperative days. It was concluded that this perioperative regimen of methylprednisolone and ibuprofen significantly reduced pain, swelling, and trismus following the unilateral extraction of impacted maxillary and mandibular third molars.
Perioperative administration of opioids decreases pain, increases tolerance to pain, and a pleasing sedating effect. However, opioids can produce several untoward effects such as respiratory depression, nausea, vomiting, constipation and tolerance. The most common opioid preparations include oxycodone, hydrocodone and codeine. Ibuprofen and diclofenac sodium are NSAIDs with high analgesic efficacy and are commonly prescribed. Adverse effects of NSAIDs include gastro- intestinal bleeding and pain, tinnitus, and renal failure. When comparing the analgesic efficacy of opioids, NSAIDs and combinations of these medications, the combined formulations provided the highest efficacy. Surprisingly, opioids when used alone are less effective than NSAIDs in relieving pain after third molar removal and these drugs alone cannot be recommended for this purpose. Dependency is rare with the short term use of opioids.
NSAIDs act by reducing the production of peripheral prostaglandins, thromboxane A2 and prostacycline production by inhibiting COX enzyme. COX-1 receptors are found within all tissues while COX-2 receptors are present only in inflammatory and neoplastic tissues. The use of COX-2 inhibitors was initially favored over classical NSAIDs because of nearly 50% reduction in the side effects associated with NSAID administration such as peptic ulcer disease and renal failure. However, recent studies have shown that COX-2 inhibitors induce thrombosis in patients with a history of coronary artery disease or cerebrovascular accident.
The ideal agent for use after third molar surgery should alleviate pain, reduce swelling and trismus to a minimum, promote healing and have no unwanted effects. Of course, such an agent does not exist. For relief of pain, analgesics are the obvious choice. Where possible, an analgesic with additional anti-inflammatory properties should be used. Seymour et al (2003)9 reported that soluble aspirin 900 mg provides significant and more rapid analgesia than paracetamol 1,000 mg in the early postoperative period after third molar surgery.
Patients should be encouraged to take analgesics either before the onset or at the time of onset of pain or discomfort rather than waiting till the pain becomes unbearable.
Long-acting local anesthetic solutions may be of value in some situations where extreme pain is likely to be a feature in the immediate post-operative period. However, there are no strict criteria for identifying such cases pre- operatively.
Studies have shown that administering a dose of analgesic preoperatively markedly reduces postoperative pain.
SUMMARY OF PERIOPERATIVE DRUG THERAPY
Use of Antibiotics
The routine use of antibiotics in third molar removal is not recommended. However, antibiotics may be considered in the following situations-
• Presence of acute infection at the time of operation
• Significant bone removal
• Prolonged operation time
• Patient is at increased risk of infection
Use of Steroids
Where there is a risk of significant postoperative swelling, pre- or perioperative administration of dexamethasone or methylprednisolone has been shown to reduce swelling and discomfort
Use of Analgesics
Oral analgesics such as paracetamol or ibuprofen are commonly advised for outpatients. The new COX-2 selective inhibitors such as rofecoxib have superior analgesic effects without the common gastrointestinal side-effects. NSAIDs may also be helpful in reducing postoperative swelling.
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