In Canada
Health Canada has approved the drugs propofol and remifentanil for on-label use by dentists for moderate sedation. The Medical Devices Bureau of Health Canada has licensed Target Controlled Infusion (TCI) for dental use.
No dental college in Canada has approved its use. Some provinces, such as Alberta, allow the use of midazolam and fentanyl to be used by hand-bolus injection, and some provinces, such as Ontario, only allow midazolam to be used.
In Alberta, the use of a benzodiazepine (Diazepam or Midazolam) with an opioid (Pethidine and now Fentanyl) was used and taught circa 1970 at the University of Alberta Faculty of Dentistry.
The Issue:
This drug regimen of a benzodiazepine and opioid by hand-bolus administration is over 50 years old and no longer meets the needs of modern dental procedures, office-based dental care or changing patient needs.
The Solution:
The use of safe, algorithmically delivered (Target Controlled Infusion pumps), ultra-short-acting i.v. agents (propofol and remifentanil) is a worldwide standard of care and has considerable merit over our current i.v. sedation methodology. Its use is supported by competency-based training and University of Alberta School of Dentistry research. This is the solution for modern dental care when intravenous sedation is required.
The solution will only be realized with the support of the Alberta Government, the College of Dental Surgeons of Alberta, and dentists who provide intravenous sedation services.
Expert Insights:
I have invited two worldwide experts on using office-based TCI intravenous sedation to address some of the most commonly expressed misconceptions or biases against TCI sedation by dental college regulators and Ministries of Health in Canada.
- Dr. Don Macalister: An oral surgeon in Auckland, New Zealand, he pioneered the use of TCI sedation in New Zealand and is a specialist dental clinician, educator, researcher, and international lecturer on TCI sedation.
- Dr. Rohit Bedi: A general dentist in Christchurch, New Zealand, he is a sedationist/operator who utilizes TCI sedation, a general dental clinician, an educator, and a researcher.
Dr. Don Macalister’s Response
Q: The rising cost of healthcare and overwhelmed hospitals in Alberta are nearing a crisis and causing concerns, especially in rural areas. Will delivering office-based dental sedation with TCI solutions provide patients with optimal care and a financial advantage, thus reducing the need for hospital care?
Yes, our experience has been that office-based sedation using propofol and remifentanil with Target Controlled Infusion (TCI) pump administration has vastly increased accessibility to care. TCI’s ability to produce steady brain concentration of the drugs enables very accurate titration and positioning of the patient at a stable point on the continuum of sedation. This provides GA-like operating conditions with a safe, responsive patient.
When aware of the provision of TCI procedural sedation I provided, the largest third-party health care provider in New Zealand adopted a new tier of payment, sitting between manual intermittent bolus sedation and full general anesthesia (GA). This recognition and the willingness to fund it at a higher cost than traditional methods of sedation represented considerable savings on their GA/Theatre spend. My practice rarely needs to resort to a full GA, as TCI provides a suitable means of treatment at approximately half the cost, less downtime, and faster recovery.
For the uninsured, it removes many barriers to treatment, as procedures can be carried out in dental offices instead of requiring a full theater and recovery facility.
Q: Will office-based dental sedation improve access to care for special needs and rural patients?
Yes, TCI is especially valuable and viable for rural or poorly served locations. Many treatments previously requiring a GA can now be carried out under very stable and accurate procedural sedation using TCI. The process provides excellent control and safety for special needs. In my practice, I treat a range of neurological disorders, including Huntington’s, Parkinson’s, and Cerebral Palsy cases, with great success.
Q: Is the hospital situation similar in New Zealand?
The New Zealand hospital dental service faces an overwhelming demand, particularly for extracting decayed teeth in children requiring full GA due to their young age. While this remains a challenge, TCI provides the ability to handle cases for children aged six years and older, reducing the reliance on general anesthesia for extractions and other interventions.
Q: Has there been an impact of using total intravenous sedation (TIVS) and total intravenous anesthesia (TIVA) for treatment within and outside hospital care?
Yes, hospitals using TIVA have reported faster recoveries and reduced time in the Post-Anesthesia Care Unit (PACU). Outside hospitals, oral and maxillofacial practices utilizing TCI sedation have seen a marked decrease in general anesthesia use, faster patient turnaround times, and quicker recoveries, often straight from the dental chair.
Q: Does New Zealand’s training program for TCI sedation include other medical healthcare providers?
Yes, the program has expanded to include registered nurses and general medical practitioners who use sedation in outpatient settings. Although gastroenterologists primarily use manual bolus techniques, many are transitioning to propofol for its superior attributes. TCI pumps, controlled by pharmacokinetic (PK) software, offer a safer, more precise alternative to manual methods.
Q: Would TCI technology be advantageous for office-based care outside hospitals, whether for sedation or anesthesia?
Yes, TCI allows for precise adjustments to sedation levels in real time, ensuring safety and rapid recovery. The fast offset of TCI-administered drugs means over-sedation is quickly resolved by reducing or stopping the infusion. Recovery times are comparable to, or faster than, using antagonists for traditional sedation drugs.
Q: How do dental insurance companies view TCI sedation compared to basic IV sedation?
Insurance companies favor TCI sedation for its cost savings and versatility over general anesthesia. In New Zealand, insurers immediately created a cost tier to promote its use, recognizing its significant financial and operational benefits.
Q: One misconception is that propofol invariably leads to deep sedation. Is this true?
No, the misconception stems from the method of administration. Hand-bolusing propofol makes achieving steady-state concentration difficult. TCI technology, however, ensures safe and steady sedation by continuously adjusting the drug dosage based on patient-specific covariates, such as age, weight, and height.
Q: Can only anesthesiologists administer propofol in specialized clinics?
Evidence suggests this is not true and, in some cases, relying solely on anesthesiologists has led to less safe sedation practices. Proper training enables non-anesthesiologists to use propofol safely and effectively in office-based settings.
Q: Are propofol and remifentanil unsafe for moderate IV sedation in dentistry?
No, scientific evidence and decades of experience demonstrate the safety of TCI-administered propofol and remifentanil for moderate sedation. In over 20 years of using TCI, I have not encountered adverse events, and the collective experience of our trained users exceeds 100,000 cases with excellent outcomes.
Propofol does not have a reversal agent; thus, it is unsafe for dentists’ usage.
No, it doesn’t have a reversal agent, nor does it need one. Even if one were available, it wouldn’t be necessary. Propofol’s extremely short half-life and rapid offset allow for safe cessation of sedation simply by stopping drug administration via the TCI pump. This typically results in a responsive patient within 30-60 seconds, aided by light stimulation. In many cases, stopping the drug is faster than sourcing, preparing, and administering an antagonist, even if one exists. The offset for remifentanil is even quicker for all age groups.
Midazolam and fentanyl are the standard of care in Canada, and regulators believe they meet all of the dentist’s needs for modern dental procedures. Would that be your experience?
They don’t meet all dentists’ needs. They have a very poor recovery profile and a half-life of 3-5 hours. Short-case sedation (under 20 minutes) is challenging, and longer cases (over 90 minutes) are equally limited.
Midazolam’s time-to-peak effect is 10-15 minutes, leading to potential dose stacking and over-sedation with hand bolus administration. This forces dentists to either wait for drug levels to fall or use a reversal agent, often halting treatment for the day.
In contrast, TCI allows for safe titration and real-time adjustments of sedation levels, ensuring accuracy, safety, and faster recovery.
For dental procedures that last under 15 minutes or over 3-4 hours, would midazolam and fentanyl sedation be appropriate?
TCI excels in both scenarios. For short cases, TCI delivers a fast, controlled onset, allowing the patient to return to pre-sedation levels of awareness within 15 minutes. For long procedures, TCI provides unparalleled stability by continuously adjusting drug delivery to maintain a steady brain concentration, ensuring safety and effectiveness throughout.
One oral surgeon who uses propofol and remifentanil with a manual infusion pump stated he sees frequent bradycardia. Is this your experience with TCI and moderate sedation?
Bradycardia is not a frequent issue with TCI. The problem likely arises from using a syringe driver or manual pump without algorithmic control. Unlike TCI, such methods lack precision and adaptability, leading to inconsistent drug administration. TCI’s algorithmic adjustments minimize such risks.
Regulators are concerned about risk mitigation in office-based sedation. How has New Zealand addressed this concern?
New Zealand regulations focus on the intended level of sedation, mandatory monitoring, and operator competencies rather than the specific drugs used. Practitioners must be trained in their chosen technique, maintain resuscitation qualifications, and meet strict monitoring standards.
(Editor’s note: The College of Dental Surgeons of Alberta restricts drugs like propofol, remifentanil, and ketamine, only allowing hand bolus administration into a freely running IV line.)
What adverse events might occur with TCI sedation, and how do they compare to hand-bolus techniques?
Adverse events like over- or under-sedation are less common with TCI due to its inclusion of patient covariates and algorithmic drug delivery. TCI allows continuous monitoring and real-time adjustments, providing stable sedation levels throughout the procedure. In rare cases of hypotension, the propofol target concentration can be adjusted downward while increasing remifentanil to maintain a normotensive state.
Would you outline your training protocols for TCI sedation for Canadian regulators?
Yes, we are open to sharing our training protocols, which are modeled on the Euro SIVA (Society for Intravenous Anesthesia) guidelines, used with permission.
How long has TCI sedation been practiced in New Zealand, and how many cases have been completed?
TCI sedation has been used in New Zealand for over 20 years and is growing rapidly. Dentists and specialists have collectively completed over 100,000 cases.
What are the key benefits of TCI sedation for patients, your sedation team, and regulators?
- Patients: Safer drug administration, faster recovery, reduced barriers to treatment, and improved overall experience.
- Sedation team: Greater precision, versatility, and efficiency for a wide range of procedures.
- Regulators/Ministry of Health: Reduced reliance on general anesthesia, cost savings, and improved access to care.
Can the same results achieved with TCI sedation be replicated with midazolam and fentanyl?
No. While I have extensive experience with midazolam and fentanyl, they cannot match TCI’s precision, efficiency, or safety. Midazolam and fentanyl are slower acting, have longer half-lives, and present higher risks of excess or inadequate sedation.
If you had the opportunity to speak to Alberta’s Minister of Health or the College of Dental Surgeons of Alberta, what would you say?
I would emphasize the advancements in modern sedation offered by TCI, highlighting its safety, accuracy, and cost-effectiveness. Comparing TCI to outdated manual techniques is a disservice to innovation. TCI represents the future of sedation, combining pharmacokinetic precision with improved patient outcomes.
(Editor’s note: PG09 is the Australia New Zealand College of Anesthetists’ Guideline for Procedural Sedation; anzca.edu.au.)
Would you be willing to answer questions from the Dental College or Ministry of Alberta Health?
Yes, I would be happy to provide additional insights or clarifications as needed.
Dr. Rohit Bedi’s response
The rising cost of healthcare and overwhelmed hospitals in Alberta are nearing a crisis and causing concerns, especially in rural areas. Will delivering office-based dental sedation with TCI solutions provide patients with optimal care and a financial advantage, thus reducing the need for hospital care?
Will office-based dental sedation improve access to care for patient care, especially for special needs patients and rural patients?
Office-based TCI sedation has a large impact on patients and public health. Referrals to hospitals for patients needing dental work are often made when their needs cannot be met under local anesthetic. This is either because of the extent of work required cannot be managed predictably using intermittent hand bolus techniques due to the limitations on working windows when using such techniques or the inherent unpredictability associated with such methodology. This is especially true for the cohort of younger patients and those with special needs for whom a more predictable and measured approach is required.
TCI sedation circumvents these issues by providing the general dental practitioner the tools to manage many of these cases outside safely and predictably of the hospital environment.
Is the hospital situation similar in New Zealand?
The health system in NZ is under considerable pressure with long waiting lists for dental treatment for patients with very stringent inclusion criterion for availing hospital-based care.
Has there been an impact of using total intravenous sedation and total intravenous anesthesia for treatment within hospital care? Outside of hospital care?
The use of total intravenous sedation (TIVS) has increased access to outside of hospital care for patients with complex needs. We have recently trained 2 special needs dentists in the use of the TCI technique. Currently, there is limited uptake of TCI in the hospital environment, but there is a significant increase outside of the hospital environment which conversely reduces burden on the hospital lists.
Yes. We have extended the training program to local and overseas-based medical and allied health practitioners. As of the time of this writing, in the 3 editions of the course run so far, we have had 2 medical doctors, 3 anesthetic technicians, 4 maxillofacial surgeons and over 20 registered nurses attend the course. We have also had inquiries from a doctor working in a hospital setting with burn victims requiring sedation for changes of dressing who is currently enrolled for a lower tier IV sedation course with ourselves, prior to then moving to TCI sedation training.
Propofol and remifentanil, administered with TCI pump technology, are the only systems of care that can provide all four levels of sedation and anesthesia—minimal, moderate, deep sedation, and general anesthesia.
Minimal and moderate levels are considered sedation, whereas deep sedation and general anesthesia are considered anesthesia.
Would TCI technology be considered the more appropriate and advantageous solution for office-based care outside of a hospital, whether for intravenous sedation or anesthesia?
In NZ, the dental council practice standard only allows for the administration of minimal and moderate sedation by dentists/dental specialists. Our position remains that the only way to guarantee minimal and moderate sedation consistently and predictably is the use of TCI sedation. This is due to the ability to eliminate variables using the latest PK-PD algorithms (Eleveld 2.1) and then being able to titrate at exceedingly low target brain concentrations while watching the patient for effect of drug, before moving up another increment. The use of short and ultra-short acting infusion drugs allows us to see the effect of the ‘dose’ of the drug administered in near real time and then adjust infusion rates to compensate for depth of sedation. The monitoring of the patient using advanced physiological monitoring which includes monitoring brain activity using processed EEG (Bispectral index or BIS) as well as verbal contact and assessing RAVOC™ (responsiveness, airway, ventilation, oxygenation and circulation) by 2 additional team members qualified in TCI sedation monitoring enhances patient safety beyond what is possible with conventional sedation methodology.
The true strength of TCI models is the ability to maintain the state of sedation once it is attained as the TCI pumps effectively run three superimposed infusions catering to offset varying blood and brain concentrations of the drug. The sedationist can then modulate these by moving up or down the spectrum in increments as small as 0.1 nanogram of the drug.
This allows for titration and safety that just isn’t possible with any intermittent hand bolus technique.
How do dental insurance companies approach basic i.v. Sedation and the more advanced TCI sedation for patient coverage?
Southern Cross Insurance, one of the largest dental insurance providers, has acknowledged the benefits of TCI sedation and its distinction from standard sedation administered using Midazolam and Fentanyl via intermittent hand bolus techniques. They have allocated a separate price category for this technique for certain practitioners who are experts in TCI sedation, including members of our teaching faculty, Drs. Macalister and Chrisp.
One misconception by dental colleges is that when propofol is used for sedation, it invariably leads to deep sedation.
This is a common misconception among the wider medical fraternity, stemming from an association of the TCI technique using propofol with more rudimentary and commonplace administration of propofol via intermittent hand bolus or standard infusions in hospital environments. These traditional techniques lack the precision of PK-PD-based TCI pumps and often result in deeper-than-intended sedation, as manually administering drugs does not account for individual physiological variations and drug sensitivity.
TCI algorithms, such as the Eleveld model (developed using data from over 30 studies and 1,000+ patients), account for these variations through allometric scaling and maturation functions that factor in size, age, and physiological changes. TCI pumps allow drug administration to begin at low receptor-site targets (in the brain), enabling gradual dose increases to achieve the desired sedation depth without drifting into unintended deep sedation. When deeper-than-intended sedation occurs, the rapid offset of TCI drugs allows for immediate correction, ensuring safety.
The source of this misconception is not the drug propofol but rather the technique by which it is being administered.
Propofol can only be administered by an anesthesiologist in specialized clinics.
This statement is untrue. In New Zealand, TCI sedation using propofol and remifentanil has been safely administered to over 100,000 patients without fatalities or major adverse events requiring hospitalization. As a general dentist, I sedate over 300–400 patients annually using the TCI technique in private practice. With appropriate staffing and training, this technique is exceedingly safe and effective.
Propofol and remifentanil are unsafe for use in moderate intravenous sedation in dentistry?
Refer to the explanation above.
Propofol does not have a reversal agent; thus, it is unsafe for dentists’ usage.
The ultra-short-acting nature of the drugs, along with the stable brain concentrations achieved via the TCI technique and the RAVOC™ monitoring approach, allows for immediate correction of unintended deep sedation. The absence of reversal agents is, therefore, not a safety concern.
Having used reversal agents in the past to rescue unresponsive patients, I can attest that the time required to open an ampoule, draw up the reversal agent, and administer it is 60–180 seconds or longer. By contrast, with the TCI technique, stopping the infusion with the push of a button and supporting the patient’s airway allows drug concentrations at the brain receptors to devolve, returning the patient to a lighter sedation plane within approximately 60 seconds.
Once a patient has been reversed using a reversal agent for Midazolam/Fentanyl you cannot restart the sedation. Whereas, with TCI sedation once you have regained responsiveness and assessed physiological parameters to be safe, you can simply re-enter the sedation by setting a lower target on the TCI pump than the one that resulted in the deepening of sedation. This allows for dynamic correction much quicker than a reversal agent.
Midazolam and fentanyl are the standard of care in Canada, and regulators believe they meet all of the dentist’s needs for modern dental procedures. Would that be your experience?
Absolutely not. While midazolam and fentanyl sedation provide a reasonably high margin for safety and are widely available, they are not the standard of care. The technique of intermittent hand-bolusing drugs to an increasingly complex patient cohort is crude and outdated. It does not allow for predictable sedation or longer working windows, which are critical for administering sedation for restorative care. When access to modern sedation techniques is withheld, patients often let their dentition deteriorate until surgical removal of teeth becomes necessary. Historically, hospital-based midazolam sedation was used for short surgical procedures, but evolving patient needs and medical complexity have rendered this approach insufficient.
For dental procedures that last under 15 minutes or over 3-4 hours in duration, would this be an appropriate use of midazolam and fentanyl sedation?
As previously mentioned, the long decrement times of midazolam and fentanyl make them unsuitable for longer procedures. Dose stacking occurs when the drugs are ‘topped up,’ leading to accumulation within the body that persists longer than the patient’s stay in the dental office. This compromises the patient’s post-procedural recovery and ambulation.
With TCI sedation, we can handle both short and long procedures effectively. Patients can be discharged directly from the dental chair due to the rapid recovery enabled by the TCI technique. The context-sensitive half-life of TCI drugs, such as propofol and remifentanil, ensures rapid devolution of drug concentrations, even after prolonged procedures. At our practice, we see no difference in discharge time for procedures lasting 20 minutes versus 4 hours.
One oral surgeon using propofol and remifentanil with a manual infusion pump stated they see frequent bradycardia. Is this what you experience with TCI and moderate sedation?
Both propofol and remifentanil have negative chronotropic effects, which can slow heart rate, but sustained bradycardia using the TCI technique is unusual. The issue likely originates from the way the drugs are administered with a manual infusion pump, which lacks dynamic rate adjustments. With TCI, we can easily titrate the drugs to correct any bradycardic trends.
Regulators are concerned about risk mitigation in office-based sedation. How has New Zealand addressed this concern? Does your dental college share similar concerns?
Office-based sedation risk assessment is, to a degree, agnostic of the drug used, but favorable outcomes are more reliant on the staffing levels and their education and preparedness in the unlikely event of an adverse outcome. Our strategy around risk mitigation is based on upskilling practitioners and auxiliary staff and providing scenario-based training specific to office-based sedation.
It is our opinion that TCI sedation and its predictability, along with the enhanced staffing and training requirements to be able to practice TCI sedation, render it safer than conventional hand bolus techniques.
We work in conjunction with the NZ dental association as an affiliated society and the Dental Council of NZ to provide a comprehensive training program which aligns with the dental sedation practice standard. This practice standard is routinely reviewed to make sure patient safety remains the central theme.
Most recently, the TCI technique for propofol has been included in the PG09 document for both Australia and New Zealand, which is a guideline document for the administration of sedation which encompasses practitioners from both medical, dental, and allied health. This speaks to recognition of the technique and its safe use in many environments.
What would be some of the adverse events you may experience using propofol and remifentanil with TCI? Would they be similar or different from the use of midazolam and fentanyl by hand-bolus injection?
Primary adverse events in sedation are due to respiratory inadequacy which is either a central effect of a deeper plane of sedation or a direct effect from altering respiratory drive when using an opiate in conjunction. This in turn leads to cardiovascular compromise.
Such adverse events are possible with any drug used to administer sedation and, in essence, are possible and even more likely when administering hand-bolus techniques using midazolam and
fentanyl because of their inherent unpredictability. These events are also possible when using propofol and remifentanil with TCI. However, the ability to correct these events using titration with TCI is far superior as you can rapidly move bidirectionally in the sedation spectrum (increase or decrease sedation).
Propofol has a more direct effect on blood pressure by altering systemic vascular resistance than midazolam; however, given the lower levels needed for dental sedation and the propofol-sparing effect of remifentanil using the TCI technique means that this is not an issue we encounter. When we do encounter it, we are able to adjust for it using the synergism and titration available at hand using the TCI pumps which we simply cannot do using other techniques.
Would you outline your training protocols for TCI sedation for regulators in Canada?
Primary adverse events in sedation are due to respiratory inadequacy which is either a central effect of a deeper plane of sedation or a direct effect from altering respiratory drive when using an opiate in conjunction. This in turn leads to cardiovascular compromise.
Such adverse events are possible with any drug used to administer sedation and, in essence, are possible and even more likely when administering hand-bolus techniques using midazolam and
fentanyl because of their inherent unpredictability. These events are also possible when using propofol and remifentanil with TCI. However, the ability to correct these events using titration with TCI is far superior as you can rapidly move bidirectionally in the sedation spectrum (increase or decrease sedation).
Propofol has a more direct effect on blood pressure by altering systemic vascular resistance than midazolam; however, given the lower levels needed for dental sedation and the propofol-sparing effect of remifentanil using the TCI technique means that this is not an issue we encounter. When we do encounter it, we are able to adjust for it using the synergism and titration available at hand using the TCI pumps which we simply cannot do using other techniques.
How long has TCI sedation in an office-based setting been done in New Zealand? Could you estimate how many cases dentists/dental specialists in New Zealand have completed?
By my estimate, we have carried out TCI sedation in an office-based setting for over 20 years and more than 100,000 cases. This number is now increasing even more rapidly with the training course introducing more practitioners to this technique.
Could you briefly outline the benefits of TCI sedation for your patients? For you and your sedation team? For regulators or the Ministry of Health, who may consider innovation and improvement in sedation services essential for patient care?
The benefits of TCI sedation for our patients are immense on their own but even greater when considering the domino effect it has on their overall well-being and the healthcare system as a whole.
- Increased access to care, which would normally require general anesthetic, is now more available, even when general anesthetics are expensive or unavailable. This is particularly true for restorative dentistry, which often requires multiple visits, making general anesthesia harder to facilitate.
- Predictably providing minimal and moderate sedation for patients who have had failed sedation with midazolam and fentanyl.
- Predictably providing sedation for patients with special needs who cannot tolerate treatment under local anesthetic alone due to behavioral constraints or systemic disabilities.
- The ability to provide longer working windows under sedation safely, which is especially beneficial for rural patients who travel great distances for dental visits. This allows for condensed visits, meaning less downtime from their everyday activities and less time off work.
- Reduced burden on the hospital dental system by treating patients who, if left untreated, would deteriorate to the point of needing emergency visits due to infection, pain, or dental neglect.
Could you accomplish the same treatment today that you do with TCI sedation with midazolam and fentanyl?
For the many reasons listed in this document, unequivocally, no, I would not be able to accomplish the treatment I currently offer without the use of TCI.
If you had the opportunity to speak to Alberta’s Minister of Health or the Council of the College of Dental Surgeons of Alberta regarding the benefits of TCI sedation, what would you say?
I would encourage the Minister and the Council to engage Dr. Lobb’s appeal to widen the sedation portfolio currently offered in Canada for the general populace. Intermittent hand-bolus techniques are archaic and are slowly but steadily being replaced by modern and safer technologies such as TCI. We have been fortunate to be at the leading edge of this change in New Zealand and have witnessed firsthand the improvements it has brought to thousands of patients’ dental and overall well-being. There is a growing body of scientific evidence supporting the use of TCI moderate sedation using Propofol and Remifentanil in the outpatient setting. This technique is well-supported in the literature and widely used in many parts of the world. It would seem a missed opportunity for Canada not to embrace this progressive, safe, game-changing technique for procedural sedation in dental patients.
Would you consent to answer any questions the Dental College or Ministry of Alberta Health may have?
Yes. I would be happy to help by answering any questions that may come up. Thank you for your cooperation and insight in helping Canada implement innovation, new ideas, and solutions in dental sedation.
Thank you for your cooperation and insight in helping Canada implement innovation, new ideas, and solutions in dental sedation.