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Contraindications ofLittle Relevance
Below, we describe those situations where sympathomimetic vasoconstrictors have traditionally been contraindicated and that are no longer considered contraindications
or that are of little relevance, but in which it may be prudent not to use high concentrations of epinephrine (e.g.,
1:50
000 [20 μg/ml]) or administer large quantities of
epinephrine, even when not contraindicated.
Uncontrolled Hyperthyroidism
The most dramatic change in how the danger of catecholamines such as epinephrine is perceived can be seen in
patients with hyperthyroidism (uncontrolled or poorly
controlled), Graves–Basedow disease, Hashimoto thyroiditis, toxic thyroid adenoma, etc. Until recently, there
was broad consensus on the absolute contraindication of
sympathomimetic vasoconstrictors in these patients
(Allen1979; Jastak and Yagiela1983; Cawson etal.1983;
Bennett1984; Malamed1986; Roberts and Sowray1987;
Perusse etal.1992b). This criterion of maximum prudence
is based on the “sympathetic component of hyperthyroidism,” which caused 0.5–20% of these patients to experience
episodes of angina pectoris (Kotler etal.1973) and led to–
fortunately very few – cases of myocardial infarction in
patients with hyperthyroidism and no previous coronary
disease (Kotler et al. 1973; Proskey et al. 1977; Symmes
etal.1977).
However, the literature contains no cases of toxic reactions to the administration of epinephrine in patients with
hyperthyroidism (Cawson etal. 1983), and the so- called
sympathetic component is a direct effect of excess thyroid
hormone, but not of catecholamines. Furthermore, experiments with animals (Cravey and Gravenstein1965; Schoot
van der and Moran 1965; Margolius and Caffney 1965;
Cairoli and Crout 1967) and humans in which hyperthyroidism was provoked by exogenous hormone (Wilson
etal.1966; Aoki etal.1967), such as in clinical trials involving patients with hyperthyroidism (Aoki etal.1972; Varma
etal.1976; McDevitt etal.1978), were unable to demonstrate hypersensitivity to catecholamines in the cardiovascular system. Therefore, during the last 20–30
authors who considered uncontrolled hyperthyroidism an
absolute contraindication for epinephrine (Jastak and
Yagiela1983; Malamed1986) no longer do so (Yagiela1999;
Malamed2004).
Nevertheless, in the case of patients with poorly controlled
hyperthyroidism, which some authors class as ASA III
(Malamed2007), we must remember that if they present clear
signs and symptoms, then they could be ASA IV. Therefore,
they are subject to the limitations and precautions of this
years,
group, since they run the risk of developing a medical emergency known as thyroid storm or thyrotoxic crisis (nervousness, fever, sweating, palpitations, etc.), which can progress to
loss of consciousness and coma (Little 2006). In the latter
case, the patient is classified as ASA IV, which means that the
systemic disease poses a threat to the patient’s life (Greenwood
and Meechan2003).
In conclusion, at present there is no absolute contraindication for epinephrine and the other sympathomimetic
vasoconstrictors in symptomatic patients with uncontrolled or poorly controlled hyperthyroidism (ASA III),
although it is important to remember that, given their
physical status, they may be ASA IV, patients experiencing
a thyroid storm (Chapter8).
Phenothiazines andAntipsychotic Drugs
The phenothiazine family shares many common aspects,
although it can be divided into two large groups (Table10.6):
● Antipsychotic or neuroleptic drugs, also known as major
tranquilizers such as chlorpromazine, which are used to
treat severe mental disorders such as schizophrenia,
manic-
depressive psychosis or bipolar disease, severe
paranoia and mania, delirium, etc. (Hollister and
Kosek1965; Giles and Modlin1968; Fowler etal.1976;
Friedlander and Brill1986).
● Antihistamines such as promethazine, which are used as
antiallergic drugs, sedatives, and antiemetics.
These drugs can interact with sympathomimetic vaso-
constrictors to produce, in theory, alterations of heart rate
(Alvarez- Mena and Frank1973) and dizziness on standing
up (orthostatic hypotension) caused by the blockade of α
adrenergic receptors produced by these drugs (Jastak and
Yagiela1983; Yagiela etal.1985; Yagiela1999). The latter
effect can be much less obvious with norepinephrine and
levonordefrin, given that these agents act poorly against
vasodilatory β
Table10.6 Phenothiazines: two main groups.
Phenothiazine antipsychotics
Chlorpromazine Fluphenazine
Levomepromazine Perphenazine
Pericyazine Pipotiazine
Trifluoperazine Thioproperazine
Phenothiazine antihistamines
Alimemazine or trimeprazine Mequitazine
Promethazine Thiethylperazine
receptors, in contrast with epinephrine.
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164
All antipsychotic phenothiazines have a certain tendency
to cause these effects in a very moderate way. However,
they were seen to be problematic when a former antipsychotic phenothiazine, thioridazine, which produces severe
alterations of heart rate, proved fatal as a result of adverse
effects (Hollister and Kosek1965; Giles and Modlin1968;
Fowler etal. 1976). It was therefore withdrawn from the
market in 2005 (Agencia Española de Medicamentos y
Productos Sanitarios 2005; Australian Health
Department2007). Animal experiments have shown these
interactions to be of little relevance with current drugs
(Yagiela etal.1983,1985) and, to date, there has been no
evidence of a significant clinical interaction between the
two drugs groups in healthy normotensive patients (Jastak
and Yagiela 1983; Jastak et al. 1995; Goulet et al.1992;
Yagiela1999).
In conclusion, there is no contraindication for phenothiazines at the doses and concentrations used in dental
local anesthesia, although every precaution should be
taken owing to the theoretical possibility of a reaction. The
ASA status of psychiatric patients should be evaluated by
assessing the patient and reviewing their medical history.
Vasoconstrictors andOsteoradionecrosis
Radiotherapy used to treat head and neck cancer causes a
series of complications, such as mucositis, xerostomia, caries, trismus, etc. (Rothwell 1987; Carl 1993; Scully and
Epstein1996). Osteoradionecrosis, a less frequent complication (Rothwell1987; Scully and Epstein1996), is defined
as mucosal or cutaneous ulceration (loss of soft tissue
integrity) lasting more than 3 weeks, with the irradiated
bone exposed (maxilla or mandible) in the absence of cancer (Wong etal.1997).
Current knowledge of the physiology of this condition is
much improved. Radiotherapy affects all irradiated tissues,
especially bone, leaving tissue that is hypoxic, poorly vascularized, and hypocellular. In the case of trauma, such as
that resulting from tooth extraction, surgery, rubbing
against a prosthesis, etc., it is not possible to provide the
resources necessary to cure the lesion, leaving a chronic
wound that does not heal (Marx 1983; Scully and
Epstein1996). In such circumstances, trauma and bacterial
invasion are lesser factors. Spontaneous necrosis, i.e. with
no previous trauma, can appear (Marx1983; Scully and
Epstein1996; Wong etal.1997; Clayman1997).
Some authors recommend using vasoconstrictor- free
local anesthetic solutions in the irradiated areas as a coadjuvant measure to avoid increasing the risk of osteoradionecrosis (Narang and Wells 1970; Roberts and
Sowray1987), although we do not know if this measure
actually has a positive effect (Clayman 1997). However,
most reviews on management of irradiated patients do not
comment on whether the local anesthetic should contain
vasoconstrictors (Topazian 1959; Bottomley and
Ebsersole 1966; Rahn and Drone 1967; Rothwell 1987;
Carl1993; Scully and Epstein1996; Wong etal.1997), and
there are even authors who perform extractions with
epinephrine-
containing anesthetic solutions in these
patients (Marx etal.1985).
In conclusion, according to currently available information, we believe that there is no evidence for contraindicating vasoconstrictors in irradiated patients at risk of
osteoradionecrosis.
Contraindications ofFelypressin
Felypressin is a vasoconstrictor derived from the hormones
of the posterior lobe of the hypophysis (vasopressin and
oxytocin). It is marketed under the name Octapressin with
prilocaine 3% at a concentration of 0.03
Felypressin is subject to two main contraindications in
dentistry (see Chapter6):
1) Patients who have experienced a heart attack (angina
pectoris or myocardial infarction). The contraindication
is relative, since felypressin can be administered at
lower doses:
○ The reason is that the vasoconstrictor effect on the
coronary vessels decreases blood flow and oxygen
supply to the heart (ischemia) (Light et al. 1965;
Miyachi etal.2003). However, it is interesting to note
that administration of doses equivalent to 14 cartridges of 0.03 IU/ml to hypertensive patients scarcely
affects ischemia in the heart (Sunada etal.1996).
○ The United Kingdom Dunlop Committee on Safety of
Drugs recommends a maximum dose of 5 × 1.8- ml
cartridges of felypressin at 0.03 IU/ml (Oliver 1974;
Roberts and Sowray 1987). Experimental data from
dogs suggest that similar doses should be applied
(Miyachi etal.2003).
2) Pregnancy is an absolute contraindication
(Anonymous 1970; Oliver1974). The residual oxytocic
effect of felypressin stimulates the v
cause uterine contractions, thus reducing blood flow to
the placenta and increasing the risk of contractions with
premature labor or miscarriage (Anonymous 1970;
Oliver1974; Stepke etal.1994). In addition, felypressin is
used with prilocaine, a local anesthetic that can produce
fetal methemoglobinemia and worsen the situation
(Anonymous1970; Oliver1974).
IU/ml (0.54 μg/ml).
receptors, which
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