SPECIAL CONSIDERATIONS IN EXODONTIA PERTAINING TO

ANTIPLATELET DRUGS, ANTICOAGULANTS,

POST RADIATION AND THYROID DYSFUNCTION.

Presented by:-

Dr. Ketaki A. Joglekar

Guided by:-

Dr. B. M. Rudagi

Dr. Madhumati Dhawad

CONTENTS:

Special considerations in exodontia pertaining to anti-platelet drugs and anticoagulants.

Special considerations in exodontia pertaining post radiation extractions.

Special considerations in exodontia pertaining to thyroid dysfunction.

Special considerations in exodontia pertaining to anti-platelet drugs and anticoagulants.

Hemostasis:

The term hemostasis means prevention of blood loss. Whenever a vessel is severed or ruptured, hemostasis is achieved by several mechanisms: (1)vascular constriction, (2) formation of a platelet plug, (3) formation of a blood clot as a result of blood coagulation, and (4) eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.

1. Vascular constriction

Immediately after a blood vessel has been cut or ruptured, the trauma to the vessel wall itself causes the smooth muscle in the wall to contract; this instantaneously reduces the flow of blood from the ruptured vessel. The contraction results from (1) local myogenic spasm, (2) local autacoid factors from the traumatized tissues and blood platelets, and (3) nervous reflexes. The nervous reflexes are initiated by pain nerve impulses or other sensory impulses that originate from the traumatized vessel or nearby tissues. However, even more vasoconstriction probably results from local myogenic contraction of the blood vessels initiated by direct damage to the vascular wall. And, for the smaller vessels, the platelets are responsible for much of the vasoconstriction by releasing a vasoconstrictor substance, thromboxane A2. The more severely a vessel is traumatized, the greater the degree of vascular pasm. The spasm can last for many minutes or even hours, during which time the processes of platelet plugging and blood coagulation can take place.

2.Formation of the Platelet Plug

If the cut in the blood vessel is very small—indeed, many very small vascular holes do develop throughout the body each day—the cut is often sealed by a platelet plug, rather than by a blood clot.

3.4.Secondary hemostasis :Coagulation phase. and Formation of a stable fibrin clot.

Basic Theory. More than 50 important substances that cause or affect blood coagulation have been found in the blood and in the tissues—some that promote coagulation,called procoagulants, and others that inhibit coagulation, called anticoagulants.Whether blood will coagulate depends on the balance between

these two groups of substances. In the blood stream, the anticoagulants normally predominate, so that the blood does not coagulate while it is circulating in the blood vessels. But when a vessel is ruptured, procoagulants from the area of tissue damage become “activated” and override the anticoagulants, and then a clot does develop.

The mechanisms are set into play by(1) trauma to the vascular wall and adjacent tissues, (2) trauma to the blood, or (3)

contact of the blood with damaged endothelial cells or with collagen and other tissue elements outside the blood vessel.

In each instance, this leads to the formation of prothrombin activator, which then causes prothrombin conversion to thrombin and all the subsequent clotting steps. Prothrombin activator is generally considered to be formed in two ways, although, in reality, the two ways interact constantly with each other:

(1) by the extrinsic pathway that begins with trauma to the vascular wall and surrounding tissues and

(2) by the intrinsic pathway that begins in the blood itself. In both the extrinsic and the intrinsic pathways, a series of different plasma proteins called bloodclotting factors play major roles. Most of these are inactive forms of proteolytic enzymes.When converted to the active forms, their enzymatic actions cause the successive, cascading reactions of the clotting process.

Extrinsic pathway for initiating blood clotting.

Intrinsic pathway for initiating blood clotting.

THROMBOSISThrombosis is the formation, from the components of blood, of an abnormal mass within the vascular system. It involves the interaction of vascular, cellular, and humoral factors within a flowing stream of blood. Thrombosis is of greater overall clinical importance in terms of morbidity and mortality than all of the hemorrhagic disorders combined. Excessive activation of coagulation or inhibition of anticoagulant mechanisms may result in hypercoagulability and thrombosis. Injury to the vessel wall, alterations in blood flow, and changes in the composition of blood are major factors leading to thrombosis.Thrombotic disorders can be caused by an inherited deficiency of antithrombin III, heparin cofactor II, protein C, protein S, thrombomodulin, plasminogen, or tissue plasminogen activator; an activated protein C resistance (factor V Leiden); ysfibrinogenemia; and omocysteinemia. Most of these disorders have also been reported as acquired conditions. Patients should be considered for laboratory evaluation for inherited thrombotic disorders if they are younger than 45 years of age with recurrent thrombosis. In addition, patients who have had a single thrombotic event and have afamily history of thrombosis should be tested. The pathologic basis for arterial thrombosis involves atherosclerotic vascular disease associated with platelet thrombi. Thrombin is a major mediator in this type of thrombosis. Drug therapy for arterial thrombi involves agents with antithrombin and antiplatelet activity. Venous thrombi usually occur in the presence of a normal vessel wall, with stasis or hypercoagulability being the major predisposing factors. Drugs that prevent thrombin formation or lyse fibrin clots are the major agents used to treat venous thrombi.

Drugs altering the normal physiology

Antithrombotic drugs, including both antiplatelets and anticoagulants , are frequently prescribed to avoid primary or secondary thromboembolic events. When patients have to undergo invasive dental or maxillofacial treatment, dentists, oral and maxillofacial surgeons, physicians, and patients have to decide whether to continue the use of the antithrombotics or to stop it temporarily to minimize the bleeding risk associated with the surgical procedure. However, stopping this medication may lead thromboembolic events to recur, thus creating potentially hazardous situations, such as myocardial infarction, stroke, or even death

ANTICOAGULANT DRUGS

THOSE USED FOR PREVENTING CLOTTING OF BLOOD INSIDE THE INTACT VASCULATURE:

Rapidly acting: a) Heparin b) Heparanoids: Heparan sulfate, Danaparoid, Lepirudin

Slow acting / Oral anti coagulants: a) Coumarin derivatives: bishydroxycoumarin, ethyl biscoumacetate, warfarin sodium b) Indandione derivatives: Phenindione

Heparin :Standard heparin is used in high-dose therapy to treat thromboembolism and in low-dose therapy as a prophylaxis for thromboembolism. Heparin itself is not an anticoagulant. Plasma antithrombin III (ATIII) is the actual anticoagulant, with heparin serving as a catalyst. ATIII regulates coagulation by inactivating activated coagulation proteases such as thrombin and factor Xa. Heparin binds to ATIII to enhance the inactivation of these proteases Standard heparin consists of an unfractionated heterogeneous mixture of polysaccharide chains with a mean molecular weight of 12,000 to16,000 d. It inhibits factor Xa and thrombin equally. Treatment with standard heparin usually consists of intravenous (IV) infusion in a hospital setting and requires monitoring with the activated partial thromboplastin time (aPTT).

The aPTT is a laboratory test that uses a sample of the patient’s blood to measure the ability of blood to clot. A control sample is always performed with the test. A contact activator, such as kaolin, is added to the patient’s blood sample. Under normal circumstances, the blood should clot within 25 to 35 seconds. The effects of heparin are to prolong the aPTT. The goal for therapy with heparin is usually to give a dosage that will prolong the aPTT to 50 to 70 seconds. Standard heparin has a half-life of 1 to 2 hours. The only patients treated with standard highdose heparin on an outpatient basis are those receiving hemodialysis. The heparin effect lasts only several hours after dialysis because of the short half-life of the drug. Low–molecular weight heparin. The action of the low–molecular weight heparins (LMWH) is the same as for standard heparin, serving as a catalyst for ATIII.

An LMWH can be used instead of standard heparin for patients having major surgery. LMWH is now the treatment of choice for patients undergoing total hip or

knee replacement because of its superior efficacy compared with SC standard heparin in the prevention of thromboembolism LMWH is prepared by epolymerization of unfractionated heparin chains, yielding heparin fragments with a mean molecular weight of 4000 to 6000 d. LMWH preparations have greater activity against factor Xa than thrombin (factor II). LMWHs exhibit less binding to plasma proteins, endothelial cells, and macrophages than standard heparin. Thus, they have better bioavailability when administered SC, longer half-lives, and more predictable anticoagulant effects. The LMWHs are administered SC in the abdomen. The dosage for each drug is based on body weight and no laboratory monitoring is needed. The half-life of the LMWHs is about 2 to 4 hours. Treatment with the LMWHs can occur on an outpatient basis. Enoxaparin (Lovenox) is the most widely used LMWH. There are 5 other LMWH preparations: ardeparin (Normiflo), dalteparin (Fragmin), nadroparin (Fraxiparine), reviparin (Clivarin), and tinzaparin (Innohep).*

Warfarin. Warfarin (Coumadin) is an oral anticoagulant that inhibits the biosynthesis of the vitamin K–dependent coagulation proteins (factors VII, IX, and X and prothrombin). This drug is bound to albumin, metabolized by hydroxylation in the liver, and excreted in the urine. The prothrombin time ratio (PTR, defined as the patient’s prothrombin time divided by a laboratory control value) is used to monitor warfarin therapy because it measures three of the vitamin K–dependent coagulation proteins: factors VII and X and prothrombin. The PT is particularly sensitive to factor VII deficiency Therapeutic anticoagulation with warfarin takes 4 to 5 days.

Warfarin therapy is given in lower dosage (low-intensity therapy) for conditions such as the treatment or prevention of venous thrombosis. It is given in higher dosage (high-intensity therapy) to patients with prosthetic heart valves or to prevent recurrent myocardial infarction. The recommended INR goal for a patient on low-intensity warfarin therapy is 2.5 with a range of 2.0 to 3.0. For a patient on high-intensity anticoagulation therapy, the INR goal is 3.0 with a range of 2.5 to 3.5.

Antiplatelet drugs:

Platelets are an important contributor to arterial thrombi. Antiplatelet treatment has been reported to reduce overall mortality from vascular disease by 15% and reduce nonfatal vascular complications by 30%. Aspirin is the prototypical antiplatelet drug. Aspirin exerts its antithrombotic action by irreversibly inhibiting platelet cyclooxygenase, preventing synthesis of thromboxane A2 , and impairing platelet

secretion and aggregation. Aspirin is the least expensive, most widely used, and most widely studied antiplatelet drug. Dipyridamole increases cyclic adenosine monophosphate and was once used by itself for anticoagulation therapy. It was found to be ineffective, however, and is now compounded with aspirin (Aggrenox) and used for stroke prevention. These are the drugs which interfere with platelet function and may be useful in prophylaxis of thromboembolism.

Drugs interfering with the platelet function are:• Aspirin• Dipyridamole• Ticlopidine• Clopidogrel• Glycoprotein II/III receptor antagonist

Aspirin is the prototypical antiplatelet drug. Aspirin exerts its antithrombotic action by irreversibly inhibiting latelet cyclooxygenase, preventing synthesis of thromboxane A2, and impairing platelet secretion and aggregation. Aspirin is the least expensive, most widely used, and most widely studied antiplatelet drug. Dipyridamole increases cyclic adenosine monophosphate and was once used by itself for anticoagulation therapy. It was found to be ineffective, however, and is now compounded with aspirin (Aggrenox) and used for stroke prevention.

The majority of nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen and indomethacin, act as reversible inhibitors of cyclooxygenase and are used clinically in a limited extent. Salsalate and COX-2 inhibitors (Celecoxib and Rofecoxib) are examples of NSAIDs that do not appreciably affect platelet activitywhen used in therapeutic dosage.

Ticlopidine (Ticlid) and clopidogrel (Plavix) inhibit platelet activity by disrupting platelet aggregation though inhibition of adenosine diphosphate . Aspirin and clopidogrel have a synergistic antiplatelet effect as both affect platelet aggregation by different mechanisms.10 There is evidence that the effects of aspirin and dipyridamole on platelet behaviour are additive however, addition of dipyridamole to acetylsalicylic acid does not increase the incidence of bleeding events. Clopidogrel selectively inhibits ADP-induced platelet aggregation. Dipyridamole is an adenosine reuptake inhibitor and phosphodiesterase inhibitor with antiplatelet and vasodilating activity.The action of dipyridamole is reversible. Aspirin begins irreversibly inhibiting platelet aggregation within one hour of

ingestion and clopidogrel within two hours; this lasts for the life of the platelets (7-10 days).5,7 The effect is only overcome by the manufacture of new platelets. 8

Complete recovery of platelet aggregation may occur in 50% of cases by day three and in 80% of cases by day four.

A newer class of antiplatelet drugs, fibrinogen receptor (platelet cell surface glycoprotein IIb and IIIa) inhibitors, is now available for clinical use. Tirofiban(Aggrastat) is the most commonly used drug from this group. Other fibrinogen receptor inhibitors include abciximab (ReoPro) and eptifibatide (Integrilin).

PRE OPERATIVE AND POST OPERATIVE EVALUATION:

HISTORY AND CLINICAL EXAMINATION

LABORATORY SCREENING TESTS

LABORATORY SCREENING TESTS:

Ivy bleeding timeThis test is performed by placing a blood pressure cuff on a patient’s arm and inflating it to 40 mm Hg. A small incision is made on the patient’s arm, and every 30 seconds the blood is blotted gently with filter paper until bleeding has stopped. The filter paper must not touch the wound. This test is intended to measure platelet function, but it is neither sensitive nor specific. For this reason, its use is declining and at some institutions has been eliminated completely. Platelet counts 100,000/microL, low hematocrit, aspirin, other platelet inhibitory drugs, and certain other medications can prolong the bleeding time. Many variables influence the result, including skin thickness, temperature, blood vessel characteristics, type of blade, orientation of the incision (horizontal versus vertical), location of the incision, handedness, and other features.

PLATELET COUNT:- normal : 1,90,000 to 4,00,000/ µl

- thrombocytopenia elevates the bleeding time.

Assessing platelet functionWhen the platelet count and the blood film examination are normal, the bleeding time is performed to detect abnormal platelet function. The test measures platelet plug formation in vivo. Bleeding stops within 3 to 8 minutes and there is a progressive prolongation with platelet counts less than 75 × 109/l. A prolonged bleeding time is also found in patients with disorders of platelet function. The time consuming and skill-intensive platelet aggregation studies may be of help in delineating platelet functional defects. In recent years, other less labour-intensive methods may speedily provide objective information on platelet function have become available. These include PFA-100 (platelet function analyser-100). The PFA-100 can be performed in whole blood, and would readily provide the necessary information on platelet competence.

The prothrombin time (PT ) PT evaluates the formation of thrombin and fibrin through the extrinsic pathway. The test consists of adding thromboplastin as an activating agent to the sample. The factors measured in this test are I, II, V, VII, and X. Some of them are vitamin K dependent, such as factors II, V, and VII, which are also depressed by warfarin sodium. The normal value range is 11 to 15 seconds.

Activated partial thromboplastin time

- The aPTT measures the time required to generate thrombin and fibrin via the intrinsic and common pathway. The normal aPTT ranges from 25 to 35 seconds. The clinical application of these tests involves screening for deficiency of prekallikrein, high molecular weight kininogens, and factors I, II, V, VIII, IX, X, XI, and XII, XI, IX. PTT reagent (phospholipid with an intrinsic pathway activator, such as silica, celite, kaolin, ellagic acid) and calcium are added to patient plasma, and the time until clot formation is measured in seconds. Phospholipid in the PTT assay is called ‘‘partial thromboplastin’’ because TF is not present. TF is present with phospholipid in (complete) thromboplastin reagents that are used for PT assays.

Specific assays for coagulation factors:Assays are available for measuring factors VIII, IX, XI, XII, and VWF. Factor XIII activity can be assessed by testing for clot solubility in urea. Only uncross-linked clots are soluble, suggesting factor XIII deficiency.

PROTHROMBIN TIME RATIO and INR:

The accuracy of the PT is known to be system dependent. Because of this dependency, the World Health Organization has addressed this system variability problem by (1) the establishment of primary and secondary international reference preparations of thromboplastin and (2) the development of a statistical model for the calibration of thromboplastins to derive the International Sensitivity Index (ISI) and the INR.

Patient’s prothrombin time divided by a laboratory control value.

PTR = Patient PT

Control PT

Was used to monitor warfarin therapy. However it’s been shown to be imprecise due to:

1. There may be little comparability of PT values performed in different laboratories.

2. Variability of PT values is attributable to differences in the source of thromboplastin (human brain, rabbit brain), the brand of thromboplastin used and the type of instrumentation.

In 1985, International Committee on Thrombosis and Homeostasis requested that all lots of thromboplastin have an indication of their ISI.

The ISI establishes the reference standard of 1.0 based on human brain derived thromboplastin.

ISI > 1.0 = less sensitive thromboplastin

ISI < 1.0 = more sensitive thromboplastin.

This allows a uniformity of the results from different labs by the introduction of INR.

INR:

- INR = Patient PT ISI

Control PT

- determination of coagulation status of patient on warfarin therapy:

1. INR determination weekly for 1st month

2. INR determination biweekly for 2nd month.

3. INR determination every 3 months then onwards.

4. INR should be 2 to3.5

5. Use of prothrombin time (PT) and the prothrombin ratio (PTR) as measures of anticoagulation status, rather than prothrombin time expressed as the INR.

6. One and half times the control. (eg – 18secs with a control of 12 seconds) is acceptable.

Patients taking antiplatelet agents and dental treatment:

Aspirin. The best screening test for the effect of aspirin on coagulation is the platelet function analyzer (PFA-100).29-35 If this is not available, then the Ivy bleeding time can be used. Although aspirin affects platelets and the coagulation process through its effect on platelet release, it does not usually lead to a significant bleeding problem unless the bleeding time is greater than 20 minutes.

Low dose aspirin therapy (100mg per day or less) should not be interrupted for outpatient dental procedures.

When intra / post-operative bleeding does occur, local haemostatic measures are usually effective.

When patients are taking dual antiplatelet therapy either their interventional cardiologist should be contacted for advice or the patient should be referred to a dental hospital or hospital-based oral/maxillofacial surgeon.

If surgery must be performed under emergency conditions and the bleeding time is in excess of 20 minutes, 1-desamino-8-D-arginine vasopressin (DDAVP) can be used to shorten the bleeding time. The mechanism of action is not clear but may involve enhancement of von Willebrand’s factor activity.36,37 DDAVP can be given parenterally or by nasal spray one hour before surgery. Parenterally the dose of DDAVP is 0.3 μg/kg of body weight, with a maximum dose of 20 to 24 μg. The nasa spray, Stimate (desmopressin), contains 1.5 mg/mL of DDAVP and is given

in a dose of 300 mg/kg. Usually, one dose will be sufficient. DDAVP should be used with caution in older patients with cardiovascular disease because of the potential risk of drug-induced thrombosis This should be done in consultation with the patient’s physician or hematologist.

ADP and fibrinogen receptor inhibitors. Patients taking clopidogrel (Plavix) or fibrinogen receptor inhibitors can have invasive dental procedures performed without altering the dosage. If excessive bleeding occurs, it should be controlled by local measures. If major oral surgery is planned and excessive bleeding is anticipated, clopidogrel should be discontinued 7 days prior to surgery.

Anticoagulant drugs and dental treatment:

Patients taking Warfarin

Warfarin is the most commonly used oral anticoagulant, and there are several currently accepted indications for its use.4-6 Planning dental extractions on warfarinised patients presents a dilemma. Altering the anticoagulant treatment preoperatively, in order to reduce the risk of serious haemorrhage following extractions, puts the patient at risk of thromboembolism.

Use of prothrombin time (PT) and the prothrombin ratio (PTR) as measures of anticoagulation status, rather than prothrombin time expressed as the INR.

The international sensitivity index (ISI) for different thromboplastin reagents used in measuring prothrombin time is obtained by calibration against WHO reference preparations. The INR takes into account the source of the thromboplastin, and is calculated using the ISI, allowing for accuracy and conformity in reporting laboratory results of warfarin effect across a range of different techniques. For monitoring patients on warfarin, the INR is now considered as the only acceptable index of anticoagulation status.

In the past, stopping anticoagulant treatment for 2–6 days before dental extractions has been suggested, since severe haemorrhage may occur postoperatively. However, ‘rebound hypercoagulation’ has been reported after interruption of the anticoagulant treatment for the purpose of carrying out extractions. Still, others recommended stopping the anticoagulant medication and replacing it with heparin. Others recommended reducing the intake of anticoagulant medication before extraction and performing the procedure only with a prothrombin time (PT) ratio of 1.5:2. A review by Wahl21 found little to no risk of significant bleeding following dental surgical procedures in patients with a PT of 1.5 to 2 times normal. Wahl also reported evidence that there was little risk of bleeding complications even if the PT is up to 2.5 times normal, and a greater risk of adverse outcome is associated with stopping anticoagulation. Giglio has suggested the following guidelines: single tooth extraction or minimally invasive procedures are indicated if the INR is less than 4; in cases where moderate bleeding is expected, reduce the INR, depending on the risk to the patient; adjustwarfarin to achieve an INR less than 3 if significant bleeding is expected; and avoid any surgery if the INR is greater than 5.

The dentist must be aware that certain dugs will affect the action of warfarin. Drugs the dentist may use that potentiate the anticoagulant action of warfarin are acetaminophen, metronidazole, salicylates, broad-spectrum antibiotics, erythromycin, and the new COX- 2–specific inhibitors. Other potentiating drugs are cimetidine, chloral hydrate, phenytoin, propranolol, and thyroid drugs such as

thyroxine (T4) and triiodothyronine (T3). Drugs the dentist may use that will ant gonize the anticoagulant action of warfarin are barbiturates, steroids, and nafcillin.

Patients taking LMWH:

Outpatients taking LMWH can have invasive dental procedures performed without altering their LMWH medication. Any excessive postoperative bleeding can be managed using local measures. These patients are not typically monitored with laboratory tests such as PT or aPTT. If significant bleeding is anticipated,based on the type of surgery planned or a high dosage of LMWH, the LMWH could be discontinued for one day by the patient’s physician (half-life is 2 to 4 hours) and the surgery performed the next day. The LMWH therapy could then be restarted once hemostasis is achieved. Another option is to wait until the LMWHtherapy has been completed and then perform elective invasive procedures. Consultation with the patient’s physician is recommended before selection of any of these options.

Patients taking standard heparin:Most patients treated with standard heparin are hospitalized and will be placed on warfarin once discharged. Dental emergencies in these hospitalized patients should be treated as conservatively as possible, avoiding invasive procedures. In contrast, patients undergoing hemodialysis are administered heparin in an outpatient setting. Since the half-life of heparin is only 1 to 2 hours, these patients can safely receive invasive dental treatment the day after dialysis.

Special considerations in exodontia pertaining post radiation extractions.

There is a broad spectrum of radiation types, however the particular one of clinical interest is known as ionizing radiation. This is defined as radiation of sufficient energy that when applied to an atom is capable of dislodging an orbiting electron that can subsequently cause a biologic effect when it interacts with cellular components such as H2O or DNA.

MOLECULAR AND CELLULAR RADIATION BIOLOGYMechanisms of Radiation Cellular KillThe most significant radiation-induced damage that results in the death of the cell occurs in the DNA molecule. X-rays or gamma rays interact with the orbiting electrons of an atom, causing their excitation and ejection as fast electrons. These in turn will react with water molecules with the formation of highly reactive free radicals, which in turn cause DNA damage known as an indirect action. Alternatively, the fast electrons can directly damage DNA and this is known as a direct action. Many of the DNA damages can be repaired, however certain lesions are not rectified and this results in the cell undergoing perhaps one or two subsequent cellular divisions before entering a stage where it cannot undergo further mitosis and thus cannot reproduce, a condition defined as cell death.Another notable radiation effect that can result in cell death involves changes occurring in the cellular membrane in particular and perhaps also with the nuclear DNA, which ultimately results in programmed cell death known as apoptosis.

Oxygen EffectThe ability of ionizing radiation to cause biologic change is very much dependent on the amount of oxygen present in the tissue environment. Oxygen is the most potent radiosensitizer known at this time. Cells in a 100 percent oxygen environment are 3 times more radiosensitive than cells in complete anoxia. It is the oxygen that reacts with the DNA damage and prevents its repair which ultimately leads to cellular death.

EFFECT OF RADIATION ON TISSUES• The irradiated mandible, periosteum, and overlying soft tissue undergo

hyperemia, inflammation, and endarteritis. • These conditions ultimately lead to thrombosis, cellular death, progressive

hypovascularity, and fibrosis. • The radiated bed is hypocellular and devoid of fibroblasts and osteoblasts.

EFFECT OF RADIATION ON NORMAL TISSUES:1. Acute effects: Mucositis Loss of taste and smell Secondary or 'opportunistic' infections

2. Late effects include damage to the salivary glands with resultant xerostomia, damage to the dentition, mucosal and muscular fibrosis, soft tissue ulceration and necrosis, ORN, cartilage necrosis, and damage to the eye, ear, and central nervous system.

CONTRIBUTING FACTORS:• Dental trauma.• Tumor location. • Radiation dosage. • Elapsed time since radiation. • Nutrition.• Alcohol and tobacco use, and • Concomitant surgery and chemotherapy.

Pre-radiation tooth extraction: 21 days before commencement of radiotherapy (recommended time for bone

revascularization and healing to take place) A minimum interval of 14 days' healing time between tooth extraction and

the onset of radiation reactions is recommended (radiation reaction established at 10 to 12 days after initiation of external beam radiation).

Post radiation extractions: The first 4 months after radiotherapy represents a time of tissue recovery

without the accumulation of the 3-H tissue effects. After 4 months, development of the 3-H tissue will begin to affect healing.

After this time, the standard protocol of HBO is recommended for elective surgery in irradiated tissues.

HBO PROTOCOL - MARX: 20 sessions at 2.4 ATA for 90 minutes on 100% O2 prior to surgery. 10 sessions at 2.4 ATA for 90 minutes on 100% O2 after surgery. Daily sessions are conducted 5 to 6 days per week.

The irradiated tissues present low reparative ability and a major risk for ORN occurrence after surgical procedures compared to those in non-irradiated areas.Most authors have demonstrated higher rates of ORN when teeth are removed after radiotherapy (Horiot et al, 1981; Morrish et al, 1983; Marx and Johnson, 1987; Thorn et al, 2000), but few studies have shown increased risk for ORN development when exodontias were executed before radiation treatment (Regezi et al, 1976; Sulaiman et al, 2003) and others show similar results when dental extractions were compared before and after radiotherapy (Epstein et al, 1987; Reuther et al, 2003)

Post radiation dental care: Necessary extractions to be limited to 1-2 teeth per appointment Atraumatic technique with trimming of sharp bone margins only No attempt to raise flaps or obtain linear closure Use epinephrine is guarded Antibiotic regimen

Antibiotic regimen- Penicillin V 2gm + metronidazole 500mg 1 hr before surgery. To be

repeated QID x 1 week Clindamycin 600mg 1 hr before surgery.

then, 300mg TDS x 1 week

Special considerations in exodontia pertaining to thyroid dysfunction.

Thyroid gland dysfunction includes:

Hypothyroidism

- Primary

- Secondary

- Tertiary

Hyperthyroidism

Hypothyroidism:

The thyroid gland secretes the hormones, thyroxine (T4), triidothyronine

(T3) and calcitonin, which are vital for the regulation of most of the biochemical

activities in the body. The thyroid disfunction could be due to over production

(thyrotoxicosis) or under production (hypothyroidism) of these hormones. The

dysfunction in either form may be subclinical to an acute life threatening situation.

The clinical features of hypothyroidism vary as per the age of its

precipitation and vary in duration and the severity as per the degree of deficiency.

If it precipitates at early fetal life it results in Cretinism and if it precipitates at the

adulthood it is called as Myxoedema. The hypothyroidism could be primary,

(thyroid gland dysfunction), secondary (pituitary dysfunction) or tertiary (due to

dysfunction of hypothalamus) the myxoedema is 3-10 times more common in

females. The Basal metabolic rate is severly retarded in these patients and their

capacity to withstand stress is severely compromised. The patients who are not

adequately treated for thyroid deficiency are unusually sensitive to CNS depressant

drugs including the sedatives and opioids which are commonly used in dentistry

and oral surgery for controlling anxiety and pain. The healing potential is also

compromised in such patients.

The patient when exposed to stress or drugs can land into a myxedema coma

characterized by severe hypothermia, hypotension, hypoventilation, hypoxia and

hypocapnia.

Prevention of complications during dental procedures:

Proper identification of the patients having hypothyroidism is necessary by

obtaining detailed medical history, drug history and the clinical manifestations

present, if any, before taking such patients for the surgery, medical consultation,

and proper treatment of hypothyroidism is mandatory.

Clinical features of myxedema

Large thick tongue,

Intolerance to the cold

Muscle weakness

Dry edematous skin with puffy hands and face,

Lack of sweating,

Bradycardia, BP near normal,

Loss of hair from the brows, alopacia

Lethargy, slow to speak and react,

Hoarseness of voice

Altered menstrual pattern in females

Goiter

The patients might be sensitive to sedatives, opioids, antihistaminics, which may

be avoided, as even with the normal dose the moderate to severe overdose

reactions may be precipitated.

Management of complications

The patient may lose consciousness in the dental office because of two possibilities

a. Due to fear – in this case the consciousness is regained after the routine steps

are undertaken.

b. An undiagnosed, untreated patient having hypothyroidism looses the

consciousness and fails to respond to the resuscitative measures.

In both the situations

1. Stop the dental procedure

2. Supine position with elevation of feet

3. Prevent tongue fall

4. Periodic monitoring of vital signs

5. BLS

6. Establish IV line

7. Nasal O2 through hood or mask

8. Warming blankets to protect against hypothermia

9. Summon medical help

10.Pharmacological support symptomatically, Sodium hydrocortisone

succinate 100-2000 mg, inotropic support raises BP, atropine to correct

bradycardia, IV dextrose 25% to correct hypoglycemia.

11.Definitive treatment comprises of administration of massive doses of T3

and T4, which need to be continued for a long period even after the

recovery.

The mortality rate after myxedema coma is very high i.e. 40-50% and

thus it needs to be identified to prevent it and precautionary measures to

be taken rather than facing such severe complications.

Thyrotoxicosis

The thyorotoxicosis begins insidiously to produce a more severe crisis the

Thyroid storm. Although this is a rare emergency it can be seen in the patients with

untreated or inadequately treated patients of hyperthyroidism. The patients who

have thyrotoxicosis are unusually sensitive to epinephrine and it can precipitate

shooting of blood pressure to the dangerous proportions, severe tachycardia and

tachy-arrhythmias. Such patients should be sedated before the dental therapy but

the sedation could be ineffective if the anxiety is not psychological and is

hormonally mediated. The thyrotoxicosis is usually associated with cardiovascular

disorders. The patients who are under treatment and are euthyroid (normal levels of

thyroid hormone) do not pose increased risk during the dental treatment. Hence it

is necessary to evaluate the patients with positive thyroid dysfunction history and

take corrective steps to avoid the serious complications.

Clinical features of hyperthyroidism

1. Anxious, nervous patients.

2. Warm, wet, sweaty palms.

3. Tremors

4. Elevated BP

5. Tachycardia with raised sleeping pulse

6. Hyperdynamic circulation and functional cardiac

murmurs.

7. Exopthalmous

8. Raised body and core temperature due to increased BMR.

9. Thyroid nodules

The patients should be ideally euthyroid before starting the dental therapy.

Marginal cases can be treated with due care, with slightly increased risk. The use

of vasoconstrictors in Local anaesthetic solution should be avoided. The

epinephrine induces dysarrythmias, angina attacks and precipitate the thyroid

storm in hyperthyroid patients whose cardiovascular system is already sensitized.

Similarly drugs like atropine, which is vagolytic should also be avoided. The use of

atropine which increases the heart rate by suppressing vagus can initiate the

thyroid storm.

The ‘thyroid storm’ differs from the severe thyrotoxicosis by the presence of

hyperpyrexia (105° F) and may reach lethal level within 24 hours. This is a severe

stage of hypermetabolism and the increased body demand of energy puts additional

load on the CVS producing clinical signs and symptoms of cardiac dysarrythmias,

cardiac failure and acute pulmonary edema. Thyriod storm also produces profound

delirium, vomiting, diarrhea and vomiting leading to a stage of dehydration and

electrolyte imbalance.

Thyroid storm

Hyperpyrexia (105°C)

Cardiac arrhythmias

Acute pulmonary edema

Profound delirium

Vomiting

Dirrohea

Dehydration

Electrolyte imbalance

May be fatal if untreated

Management

The untreated and undiagnosed patient of thyrotoxicosis is likely to become

unconscious due to vasodepressor syncope and needs to be treated on lines of

treating any unconscious patient and basic life support needs to be provided.

Terminate the dental procedure.

Supine position with elevation of the feet

Start BLS

Summon medical help

Establish IV line

Nasal O2

Transfer the patient to medical emergency department

Definitive treatment with antithyroid drugs ( Propylthiouracil)

Additional measures comprise of administration of propranolol to block the

adrenergic mediated effects of thyroid harmone, high doses of

glucocorticoid to prevent acute adrenal insufficiency, O2 administration,

cold packs to reduce body temperature, IV fluids to maintain proper

electrolyte balance and the hydration.

DEGREE OF THYROID DYSFUNCTION

ASA PHYSICAL STATUS

CONSIDERATIONS

Hypo/ hyperfunction on medical therapy with no evident signs and symptoms of dysfunction

II Usual ASA II considerations

Hypo/ hyperfunction on medical therapy with evident signs and symptoms of dysfunction

III Usual ASA III considerations including avoidance of vasopressors or CNS depresssants.Evaluation for cardiovascular diseade

References:

SF Malamed. Medical Emergencies In The Dental Office. 6th Edition.

Minor Oral Surgery And Interference With Anticoagulation In Patients Taking Warfarin: A Retrospective Study. British Journal Of Oral And Maxillofacial Surgery 45 (2007) 645–647

Little JW, Miller CS, Henry RG And Mcintosh BA. Antithrombotic Agents: Implications In Dentistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002; 93: 544-51.

Farb A And Boam Ab. Stent Thrombosis Redux – The FDA Perspective. N Engl J Med 2007; 365: 984-7.