Every human being lives within the constraints of their circadian rhythm. When we wake up in the morning, sunlight shines in our eyes and stimulates the internal master clock in our brains called the suprachiasmatic nucleus (SCN). The SCN then sends signals to the hypothalamus, the pituitary gland, and the pineal gland. The hypothalamus and the pituitary gland govern appetite, thyroid function, temperature, blood pressure (BP), cortisol, growth hormone levels, and the immune system. The pineal gland begins to store the neurotransmitter serotonin, which is converted to melatonin to be released in the early evening to assist us in falling asleep.
How diagnostic technologies impact your practice and ROI
From a medical and physiological perspective, people need to work within their circadian rhythm to maintain health and longevity, and not against it. A person can alter mealtimes, exercise, and regulate the amount of blue light they see from computers and cell phones at night, all of which can alter a person’s circadian rhythm and sleep patterns to the positive or negative. Circadian patterns also regulate physiological issues such as pain, inflammation, and the time when one has the greatest chance of myocardial infarction, which all have distinct maxima and minima at different times of the day.
Relationship to dentistry
So, what role does the circadian rhythm play in dentistry? What should a dentist be aware of concerning this master metabolic clock that governs the physiology of every patient we see?
The circadian rhythm governs virtually all aspects of human physiology. At sunrise, a human being will have a significant elevation in BP, heart rate (HR), and platelet aggregation. The elevated BP and HR occur due to the morning peak in cortisol secreted from the adrenal glands, sensitizing the cardiovascular system to the effects of epinephrine and norepinephrine. By 9:00 a.m., testosterone levels will peak along with insulin sensitivity, followed shortly by the highest level of cognitive capacity and memory lasting until midafternoon. Around 5:30 p.m., a person has their maximum level of muscle efficiency and strength; by 9:00 p.m., the highest body temperature of the day; and by 10:00 p.m., a sharp increase in the level of melatonin from the pineal gland to aid in falling asleep.1-7
Overnight, during slow-wave sleep (SWS), a person will experience their highest levels of thyroid-stimulating hormone and growth hormone (from the pituitary gland), assisting in growth and repair, utilizing metabolic lipolysis for fuel.8,9 Also during the night and overnight, a person’s neutrophil and white blood cell counts will peak at about 8:00 p.m., monocytes will peak at midnight, and basophils and eosinophils between 2:00 a.m., and 4:00 a.m., corresponding to nocturnal asthma and allergic reaction activity.10,11
These functions all occur on a diurnal rhythm every 24 hours in a healthy individual. If the circadian clock of a patient is disrupted, there is great potential for systemic implications for diseases that include diabetes,12,13 cancer,14 osteoporosis,15 and immune-allergic diseases.16
Here, we’ll look at a series of physiological and medical issues related to a patient’s circadian rhythm that dentists may encounter in their patients daily. Gaining a better understanding of these issues will help dentists make better pre- and post-op decisions for treatment and practice risk mitigation to improve the health and safety of their patients.
Part of every dental visit, whether for a simple cleaning or oral surgery, is a physical exam, a comorbidity analysis, and a polypharmacy analysis.17-19 During the exam, a dentist can determine a patient’s general and immediate health, the possibility of a medical issue occurring during a dental procedure, and any potential problems with a post-op prescription.
Morning BP surge in cardiovascular disease (CVD) patients
A patient who presents to the dental office with high BP has a documented risk factor for myocardial infarction and stroke. Many patients will experience a morning surge in BP and cardiac rate related to the morning increase in cortisol. The cortisol sensitizes the cardiovascular system to a parallel rise in epinephrine from the sympathetic nervous system as part of the normal circadian rhythm.20 This morning surge is particularly dangerous for a patient who suffers from CVD.21,22 To mitigate this risk, a dentist may focus on preventive strategies to prevent heart attack and stroke in these patients during dental procedures.
For example, a particularly sharp rise in BP in the morning may be caused by a deficient antihypertensive medication regimen. Most hypertensive patients take their medications in the morning and may, therefore, have insufficient control overnight, as the patient experiences the morning cortisol and epinephrine surge.23 A patient can be questioned about the timing of their medication and asked to keep a five-day journal of evening, afternoon, and morning BP readings to share with the dentist.
Risk mitigation strategies against heart attack or stroke:
- Discuss medication timing with a patient’s physician to try to improve the BP parameters before a dental procedure.
- Schedule the procedure for a time when the patient has their lowest BP of the day, based on their existing antihypertensive regimen.
- Prescribe mild anxiolytics (such as benzodiazepines) before a procedure to prevent an increase in BP and HR before and during the procedure.24-26
Circadian management of diabetic patients
Twenty-four-hour pulsatile insulin secretion occurs in humans, with higher amplitude pulses in obese patients and patients with type 2 diabetes. A patient’s sensitivity to insulin also shows diurnal circadian changes, with abnormal rhythmicity and activity patterns in patients with obesity and diabetes. Insulin sensitivity and blood glucose levels in healthy patients are kept under very careful regulatory controls. In patients with diabetes, the aberrant insulin and glucose metabolism has significant deleterious effects on the patient’s physiology.27
The most common complication in patients with diabetes who are undergoing a dental procedure is a hypoglycemic episode. The highest risk of developing hypoglycemia will occur either during peak insulin activity or when an antidiabetic drug level exceeds the patient’s physiological needs.28
Risk mitigation strategies against hypoglycemic episodes:29
- Question the patient on the timing of their meals and medication and ask them to keep a five-day journal of the evening, afternoon, and morning blood glucose levels to share with their dentist.
- Discuss the antidiabetic medication and meal timing with the patient’s physician to try to improve the blood glucose levels before a dental procedure.
- Schedule the dental procedure for a time when the patient has their most prolonged normalized blood glucose levels during the day, around meals and medication.
- Recognize the signs and symptoms of low blood glucose levels in a patient, and have an immediate carbohydrate source to administer chairside if necessary.
Circadian management of hypothyroid patients
Hypothyroidism is defined as decreased thyroid hormone production based on aberrant thyroid gland function. It can be caused by pharmacological agents such as lithium and amiodarone, Hashimoto’s disease, surgery, and radioactive iodine. In patients with hypothyroidism, symptoms such as low metabolic rate, obesity, lethargy, and intolerance to cold are prevalent. In healthy patients, the typical circadian pattern of thyroid function shows the highest levels of thyroid hormone secretion and activity overnight between approximately 11:00 p.m. and 4:00 a.m.30,31 Currently, 8–10 million patients in the United States are being treated for thyroid disease.32
Dentists need to employ a risk management strategy to prevent cardiovascular complications resulting from treating dental patients with hypothyroid disorders who are taking thyroid hormone replacement therapy. During a dental procedure, the concurrent use of sympathomimetics (epinephrine or norepinephrine in the local anesthetic) with a patient’s levothyroxine replacement may increase the effects of sympathomimetics or thyroid hormone. This may increase the risk of coronary insufficiency with the administration of local anesthetics.
To prevent potential coronary insufficiency when administering local anesthetics:
- Ask the patient how long they’ve been on their current thyroid medication regimen to assess if they are euthyroid.
- Use adrenergic vasoconstrictors cautiously in patients with evidence of excessive thyroid stimulation from levothyroxine replacement.33,34
- Speak with the patient’s endocrinologist and suggest that the patient take the thyroid hormone in the evening so that hormone levels will be lower in the morning before administration of local anesthesia.35
Circadian management of dental and orofacial pain
It has been clinically determined that a person’s subjective measurement of pain intensity does not stay at a constant level during the day. Therefore, it is reasonable to assume that one of the causes of failed analgesia in the treatment of orofacial pain could be the failure of dentists to observe a patient’s preexisting pain patterns as they relate to their individual circadian rhythms.36
The most common type of pain a dentist encounters in patients is toothache. Pain from a toothache does not occur randomly during the 24-hour period of a day. When the duration of successful local anesthesia was examined, it was found that the midafternoon (approximately 3:00 p.m.) was the time in the circadian day that produced the longest duration of local anesthesia for patients. The shortest duration was found to be in the morning and the evening.37 When the severity of temporomandibular pain was examined on a circadian basis, most patients reported experiencing their peak pain level in the evening.38
Examining data from the discipline of chronopharmacology, it has been found that the highest bioavailability and plasma levels of nonsteroidal anti-inflammatory drugs (NSAIDs) occur in the morning at approximately 7:00 a.m.39,40 Along with these findings, unsurprisingly, the highest level and frequency of side effects encountered with NSAIDs also occur in the morning.41,42
Dental pain and NSAIDs
This is a possible strategy for patients experiencing dental pain with comorbidities or moderate polypharmacy concerns regarding NSAIDs:
For morning pain, Rx 100 mg of extended-release Tramadol (pharmakokinetic efficacy is 16–24 hours) with 500 mg or 1,000 mg of acetaminophen. This will prevent higher morning side effects common with NSAIDs.43
For afternoon and overnight pain (in the same patient), Rx 500 mg acetaminophen, with 200 mg to 400 mg ibuprofen every six hours for two to three days for acute pain. The amount of acetaminophen taken in a 24-hour time period should not exceed 3,000 mg.44 Such personalized analgesic regimens have been successful in patients to maximize pain control and minimize side effects.45,46
Conclusion
The American Heart Association has recently added “sleep” as a measure of cardiovascular health, further informing the public about the necessity of assessing a person’s circadian rhythm in medical therapy.47 Chronopharmacology is also fast becoming a component of medical assessment and treatment.48 It is time for dentistry to get on the bandwagon and implement circadian concepts into daily practice for better patient treatment and safety.
Editor's note: This article appeared in the November 2022 print edition of Dental Economics magazine. Dentists in North America are eligible for a complimentary print subscription. Sign up here.
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