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Remimazolam compared to midazolam for dental sedation: an umbrella review

G. Shaw*¹ BDS MSc (Oral Surgery) MFDS RCPS (Glasg) 
K. Taylor² PhD FDS.RCS (Oral Surgery) FDS.RCS (Eng. and Ed.) BDS BSc (Hons) Dip Con Sed 
¹Dental Surgeon, The Albion Clinic, Glasgow, G1 1RU 
²Professor of Oral Surgery, University of Central Lancashire, Preston, Lancashire, PR1 2HE 
Correspondence to: Graeme.shaw1@nhs.scot 
Shaw G, Taylor K. Remimazolam compared to midazolam for dental sedation: an umbrella review. SAAD Dig. 2024: 40(1): 3-8 

Abstract 

Remimazolam is a newly approved benzodiazepine drug used for intravenous sedation. Its efficacy and safety compared to the standard sedative drug, midazolam, have not been studied extensively, particularly in the dental setting. This study aims to compare the outcomes of remimazolam and midazolam for single-drug intravenous sedation and to discuss its potential use in dentistry. 

A search was conducted across six electronic databases for systematic reviews comparing the efficacy and safety of remimazolam and midazolam. Five systematic reviews were included from a total of 542 studies. The findings indicated that remimazolam may offer significant advantages over midazolam, including faster onset, higher procedure success rates, reduced need for rescue sedatives, shorter recovery time, improved cognitive recovery, and fewer instances of hypoxia. However, there were no significant findings regarding procedure completion or required sedation dosage. 

Overall, the evidence suggests that remimazolam has statistically significant benefits over midazolam for intravenous sedation. However, more clinical trials are needed to determine its suitability and clinical significance in dental practice. Further research is required to fully understand the potential advantages of remimazolam in the dental setting. 

Introduction 

Remimazolam is a promising benzodiazepine drug that offers potential advantages over midazolam for procedural sedation.¹ With a similar structure and mode of action to midazolam, remimazolam claims to offer a faster onset, shorter duration of action, and faster recovery from sedation.^2,3 It has a significantly shorter distribution half-life and terminal elimination half-life, resulting in a quicker recovery.³ Remimazolam demonstrates a comparable safety profile to midazolam, without an increased risk of respiratory depression, cardiovascular complications, or prolonged sedation.⁴ Additionally, it can be reversed using flumazenil, similar to midazolam.⁵ 

Prolonged recovery from sedation with midazolam poses logistical challenges for clinics and patients, requiring escorts and extended supervision.⁶ If remimazolam allows for shorter recovery times and earlier discharge, it could increase patient throughput and convenience of intravenous sedation. 

Phase III trials have been completed, and regulatory approval has been obtained for remimazolam in the EU and the UK.¹⁰ While various trials have explored remimazolam's use in colonoscopy, gastroscopy, and bronchoscopy³ there is limited research on its potential use for dental procedures. In July 2022 the Scottish Medicines Consortium assessed remimazolam for use in NHS Scotland for colonoscopy and bronchoscopy procedures.¹¹ This review found that remimazolam does indeed have certain advantages over midazolam, however, it was not approved for use within NHS Scotland due to the financial implications of using remimazolam compared to the more affordable midazolam. This does not, however, mean that it cannot be used in independent or private healthcare settings, which would include the majority of dental practices. 

The IACSD (Intercollegiate Advisory Committee on Sedation in Dentistry) released a statement indicating that practitioners experienced in midazolam use do not need additional supervised practice to administer remimazolam. They must familarise themselves with the pharmacology, dosing and indications together with an understanding of how these fit with the IACSD standards, which can be via CPD courses with appropriate aims and objectives.⁷ However, it outlines that until more substantial evidence becomes available, remimazolam should be used similarly to midazolam, with comparable requirements for escorts and restrictions on use in patients under 18. 

If remimazolam proves to be as safe and effective as midazolam with faster onset and recovery, it could offer an improved alternative for ambulatory dental surgery.⁸ Clinical trials suggest that remimazolam has a comparable safety profile to midazolam, with lower incidence of respiratory depression and hypotension.⁹ However, further research specifically focused on its dental application is needed. This umbrella review aims to comprehensively assess the evidence, identify gaps, and evaluate the efficacy and safety of remimazolam compared to midazolam in dental sedation. 

Method 

Eligibility criteria 
The eligibility criteria for inclusion in this study consisted of systematic reviews directly comparing remimazolam to midazolam in patients receiving intravenous procedural sedation, with, or without, meta-analysis. Studies that compared remimazolam to midazolam as well as placebo or other sedatives such as propofol were also included. 

Excluded from the study were articles published as abstracts, editorials, letters, notes, opinions, posters, conference articles, methods, protocols or articles with unavailable full texts. There was no time restriction placed on the included articles due to the recent development and introduction of remimazolam. Duplicate publications and articles in languages other than English were also excluded. 

Table 1 Adapted Medline search strategy 

Additionally, studies focusing solely on remimazolam when used in conjunction with other sedatives, such as propofol, were excluded. This decision was based on the fact that polypharmaceutical sedation is not standard practice in the dental setting in the United Kingdom,⁶ making these studies non-generalisable and their results inapplicable to current practice in the UK. Some primary studies used fentanyl as an adjuvant opioid anaesthetic,^12,15 these were not excluded as it was being used for intra-operative analgesia rather than the induction of sedation.¹² 

Search strategy 
A search strategy was generated and adapted as required for different databases. This strategy was adapted for use in the following databases: Medline, Dentistry and Oral Sciences Source, the Cumulative Index to Nursing & Allied Health, Academic Search Complete, Embase, and the Cochrane Library of Systematic Reviews. The reference lists of all included systematic reviews were handsearched to find any studies that may have been missed by the database search. Furthermore, PAION (the manufacturer of remimazolam) was contacted and any relevant studies were requested. 

Results

Systematic review selection 
Five studies were ultimately included in this review after full text analysis, assessment of the inclusion and exclusion criteria and evaluation of their relevance to the research question. The process of study selection has been summarised in Figure 1. 

Fig. 1 PRISMA flowchart for selecting eligible studies 

Systematic review selection 
Five studies were ultimately included in this review after full text analysis, assessment of the inclusion and exclusion criteria and evaluation of their relevance to the research question. The process of study selection has been summarised in Figure 1. 

Systematic review characteristics 
All included studies were systematic reviews, with four including meta-analysis and one opting for narrative synthesis. Three of the five studies focused on comparing the use of remimazolam to midazolam alone, while two studies also compared remimazolam to propofol. These still included data directly comparing remimazolam to midazolam, which allowed for their inclusion. One systematic review was excluded in screening phase as it grouped midazolam with propofol into a combined ‘traditional sedatives’ group, which made direct comparison with midazolam impossible.⁹ Only one study was written from a dental perspective¹² while four were written from a broader anaesthetics perspective, with a particular focus on the use of remimazolam in endoscopy, bronchoscopy or colonoscopy.^13,14,15,16 These are the procedures for which procedural sedation is most commonly used outside of dentistry, and it is on sedation for these purposes that the majority of primary studies included in the reviews were reporting. All studies were reported in English between 2021 and 2022. A full summary of study characteristics is presented in Table 2. 

Table 2 Summary of study characteristics 

Risk of bias within systematic reviews 
All systematic reviews were assessed for risk of bias using the ROBIS (risk of bias in systematic reviews) tool. Overall, three of the studies were assessed as having a low risk of bias, one study had a moderate risk of bias¹⁵ while one was considered to have a high risk of bias.¹² The results from the risk of bias assessment are shown in Figure 2. 

Fig. 2 Tabular presentation of ROBIS risk of bias assessment

Characteristics of intervention

Remimazolam was administered intravenously in all included studies. Some studies used fentanyl as an adjuvant opioid analgesic.^12,15 The chosen dose of remimazolam varied significantly across studies, ranging from 0.04 to 0.2 mg/kg given intravenously over one minute to a single intravenous bolus of 5 mg with a potential top-up of 2.5 to 3 mg.^14,17,18 Dose-finding studies (clinical trials designed to determine the optimal or most effective dose of a medication) were conducted, using incremental groups based on weight or specific doses.^17,18 One review only included dose-specific trials in their analysis, using an initial loading dose of 5 mg remimazolam with a top-up of 3 mg.¹⁴ 

Primary outcomes

Onset time 
Among the mentioned systematic reviews, only one study12 provides a direct comparison of onset time between remimazolam and midazolam. According to this study, remimazolam achieves an optimal level of sedation more rapidly than midazolam, ranging from 1.5 to 6.4 minutes. Within this review, two primary studies directly compared the onset time, with remimazolam demonstrating faster onset compared to midazolam: 1.5 to 2 minutes versus 5 minutes¹⁷ and 2.2 to 2.6 minutes versus 4.8 minutes.¹⁸ 

Procedure success 
Four reviews contained procedure success as an outcome measure. The definition of procedure success is elaborated in all studies except one¹³ and is a composite score measuring efficacy of the sedative. This score comprised between three and four outcomes. The first three of these four outcomes are consistent across the studies, with only one review¹⁴ omitting the fourth outcome: 

1. Modified Observer’s Assessment of Alertness / Sedation (MOAA/S) ≤4 on 3 consecutive measurements taken every minute 

2. Completion of the procedure 

3. No requirement for an alternative and/or rescue medication 

4. No manual or mechanical ventilation 

Fig. 3 The Modified Observer's Assessment of Alertness / Sedation (MOAA/S)

Two reviews^13,16 found that remimazolam was superior to midazolam both before and after adjustment for heterogeneity (differences or variations in the data). One study¹⁴ initially found a statistically non significant result, but upon removing a dose-finding study with various doses of remimazolam compared to a fixed dose of midazolam¹⁸ from the analysis, sensitivity analysis (a test of the robustness or reliability of the study's results and conclusions) then strongly favoured remimazolam. The dose-finding study was removed from analysis as the authors stated that there is no advantage in dosing healthy individuals by weight rather than a specific dose.¹⁴ One review, which looked exclusively at remimazolam compared to midazolam for the purposes of endoscopy, found a statistically significant improvement in procedure success after sensitivity analysis with no remaining heterogeneity.¹⁵ It follows that all four included systematic reviews which measured procedure success found statistically significant superiority in favour of remimazolam when compared to midazolam. 

Completion of procedure 
Two systematic reviews^13,14 included a distinct outcome measure for the completion of the procedure being carried out under sedation. Neither study, however, found a statistically significant association between remimazolam and the completion of procedures either before, or after, sensitivity analysis. 

Dose required for adequate sedation 
All studies defined adequate sedation as a Modified Observer’s Assessment of Alertness / Sedation (MOAA/S) score of 3 or ≤4. Only one study¹² specifically assessed the dose required for adequate sedation as a specific outcome measure, and defined adequate sedation as a MOAA/S score of 3. It was stated that the minimum dose to achieve this was either 0.04 to 0.2 mg/kg given intravenously over one minute, or a 5 mg bolus given with or without a 2.5 mg top-up dose. Another review agreed that an initial dose of 5 mg bolus followed by up to 3 mg top-up had the highest efficacy when compared to other doses.¹⁵ 

Not exceeding assigned top-up dose 
Only one review¹⁴ compared remimazolam to midazolam with regards to whether it was ever required to exceed the assigned top-up dose in order to achieve the desired level of sedation. A statistically significant result was found, with remimazolam comparing favourably to midazolam. This would suggest that it is less common for a prescribed dose of remimazolam to fail to achieve the level of sedation required in the patient without further top-ups. 

Administration of rescue medication 
Rescue medication is given if the initial dose of sedative given does not achieve adequate sedation for the completion of the surgical or investigative procedure. This is generally given as an unassigned top-up dose of the sedative in question.¹⁵ However, rescue medication may have been given as an alternative sedative; as such it was measured as a different outcome measure than assigned top-up dose. The use of rescue medication in patients receiving remimazolam or midazolam was compared in three of the included systematic reviews. One review found that the use of rescue medication was significantly reduced in the remimazolam group.¹³ Another carried out sensitivity analysis and found a significant reduction in the need for rescue sedatives both before and after this.¹⁴ One review quantified this reduced need for rescue sedatives as a reduction of 2.5 to 7.5%, resulting in a smoother sedation workflow compared to midazolam.¹⁵ 

Secondary outcomes

Time to recovery 
Patients sedated with remimazolam tended to recover more quickly than those sedated with midazolam; one review13 found this difference to be statistically significant. Time to recovery from remimazolam sedation ranged from 6.8 minutes to 13.6 minutes; recovery from midazolam sedation ranged from 11.5 to 15.8 minutes.¹² The dosage regimes across the primary studies were not consistent and so the result as to specific recovery times is not reliable. 

Cognitive recovery 
The recovery of cognitive function was assessed in two systematic reviews using the Hopkins Verbal Learning Test-Revised (HVLT-R). The HVL-T is a neuropsychological assessment tool used to evaluate verbal learning, memory and recognition abilities by presenting word lists and measuring immediate and delayed recall (around 20 to 25 minutes later) of the presented words as well as recognition accuracy.^13,15 It was found that patients in the remimazolam group achieved significantly faster cognitive recovery than the midazolam group.¹³ Patients who were administered remimazolam demonstrated a shorter total recall and delayed recall, but it did not show any significant effect on attaining full alertness.¹⁵ 

Adverse events 
No statistically significant difference was observed between remimazolam and midazolam regarding adverse events, both when considered as a whole or when analysing individual adverse event outcomes such as decreased oxygen saturation, headache, hypotension, hypertension, or bradycardia.¹³ However, one review noted a significantly lower risk of hypotension in the remimazolam group compared to midazolam, while no significant difference was found across other adverse event outcomes.¹⁶ Another review reported a lower risk of both hypotension and other adverse events in the remimazolam group¹⁵. Overall, remimazolam appeared at least non-inferior, and potentially safer, than midazolam. 

Discussion 

The pooled findings from five systematic reviews suggest that remimazolam may offer significant advantages over midazolam in terms of speed of onset, procedure success, rescue sedatives, recovery time, cognitive recovery and certain adverse events (hypoxia). However, it is important to note that only one systematic review considers remimazolam from a dental perspective, and no primary research included in the reviews takes place in a dental setting. Therefore, caution is needed when considering these results in the context of dental practice. 

The choice of analgesic modality varies depending on the clinical context. While some primary studies used the opioid fentanyl for pain relief during sedation, in the dental setting, only local anaesthetics are typically used in combination with a benzodiazepine sedative. Opioids carry a higher risk of respiratory depression and hypotension,¹² which may impact sedation depth and adverse events. Therefore, results regarding sedation depth, recovery and adverse events in studies in which fentanyl was used must be interpreted cautiously. 

The primary research included in the systematic reviews focuses on remimazolam sedation for bronchoscopy, endoscopy, and colonoscopy, which are not analogous to dental procedures. Dental procedures often have longer durations and unique aspects such as fluids in the oral cavity which may influence adverse events associated with sedation. There is currently no clinical trial examining the use of remimazolam during dental procedures in primary care. While one randomised controlled trial in an outpatient oral and maxillofacial surgery unit showed increased procedure success rate and faster recovery with remimazolam, the difference in recovery time may not be clinically significant.⁸ Additionally, the oral surgery procedures in this trial represent only a fraction of those which may be performed in general dental practice. Therefore, further primary research focused on dental practice is needed. 

The required dose for adequate sedation with remimazolam does not appear significantly different from that of midazolam. However, the mode of administration varies across the studies. Remimazolam is either given as a measured dose based on patient weight or as a fixed bolus with, or without, subsequent top-ups. The recommended standard for the dental setting is careful titration of the sedative to patient response, which has not been investigated in remimazolam studies. Further studies in this area are necessary. 

While remimazolam has been associated with faster recovery time, there is no discussion of the time required for full psychomotor recovery, which is an important consideration. Reducing the recovery time may offer advantages to patients and their escorts in terms of supervision, work leave and transportation options. 

The use of remimazolam for single-drug sedation is only discussed for adults in the IACSD 2023 statement. However, midazolam sedation is currently available for children over 12 years of age; research on the practicalities of sedating the 12 to 18-year-old age group with remimazolam would be beneficial. 

Economic analysis is crucial to determine if the benefits of remimazolam are worth the financial cost. The economic arguments for remimazolam were not deemed sufficiently robust to approve its use within NHS Scotland for colonoscopy or bronchoscopy.¹¹ However, this assessment does not consider its use as a dental sedative, and the economic analysis may not be generalisable to the dental setting. 

Despite its drawbacks, midazolam has long been the drug of choice for procedural sedation in the dental setting due to its safety, predictability, affordability and familiarity to practitioners. To replace midazolam, remimazolam must demonstrate clear advantages while at least being non-inferior in other aspects. While remimazolam appears to have significant advantages, further primary research in the dental setting is necessary to determine if these advantages are clinically and practically significant enough for widespread adoption. 

Limitations of this study include the inclusion only of English language research, which may have restricted access to valuable findings in other languages. Additionally, there were a small number of primary studies included across the systematic reviews, and there was overlap of primary studies across the reviews, potentially biasing the results. Publication bias must be considered due to the funding sources of the included primary research. Six out of eight primary studies across the reviews were funded by PAION UK Ltd., the manufacturer of remimazolam. Therefore, the conclusions of this review must be interpreted with caution. 

Conclusion 

The available evidence suggests that remimazolam has statistically significant advantages over midazolam for intravenous sedation. However, there is a lack of research on the use of remimazolam specifically in the dental setting and whether these advantages remain clinically significant. Further trials comparing remimazolam to midazolam in the dental setting, without concomitant opioids or sedatives and with titration of the drug, are needed. 

Based on the discussed findings, future randomised controlled trials comparing remimazolam to midazolam for single-drug intravenous sedation in the dental setting are proposed. These trials should assess remimazolam's performance during longer dental procedures without concomitant systemic anaesthetics. It is important to evaluate whether remimazolam provides a meaningful advantage over midazolam; the most significant advantage may be the reduced time to recovery. Studies are needed to determine the time from induction to full cognitive and motor recovery following remimazolam sedation, in order to fully understand the potential benefits of this new medication. 

Acknowledgements 

This paper was derived from a dissertation written and submitted for consideration for the award of the degree of MSc in Oral Surgery from the University of Central Lancashire. The author would like to acknowledge his advisor, Professor Kathryn Taylor, for her help throughout this process. 

Conflicts of Interest

The author has no conflicts of interest to declare. 

References 

1. Sneyd J R, Gambus P L, Rigby-Jones A E. Current status of perioperative hypnotics, role of benzodiazepines, and the case for remimazolam: a narrative review. Br J Anaesth 2021; 127: 41-55. 
2. Illing K. Anxiety Management and Sedation in Dentistry; the next 60 years? SAAD Digest. 2018; 34: 47-50. 
3. Dao V A. Efficacy of remimazolam versus midazolam for procedural sedation: post hoc integrated analyses of three phase 3 clinical trials. Endosc Int Open. 2021; 10: E378-E385. 
4. Lee A, Shirley M. Remimazolam: A Review in Procedural Sedation. Drugs. 2021; 81: 1193-1201. 
5. Kim S H, Fechner J. Remimazolam – current knowledge on a new intravenous benzodiazepine anesthetic agent. Korean J Anesthesiol. 2023; 75: 307-315. 
6. Intercollegiate Advisory Committee for Sedation in Dentistry. Standards for Conscious Sedation in the Provision of Dental Care. 2020. Available from: https://www.saad.org.uk/IACSD%202020.pdf [Accessed 10/04/2023]. 
7. Intercollegiate Advisory Committee for Sedation in Dentistry. Remimazolam for intravenous conscious sedation for dental procedures. 2023. Available from: https://www.rcseng.ac.uk/-/media/fds/iacsd/iacsd-remimazolam-statement-130623.pdf [Accessed 18/10/2023]. 
8. Guo Z, Wang X, Wang L, Liu Y, Yang X. Can Remimazolam Be a New Sedative Option for Outpatients Undergoing Ambulatory Oral and Maxillofacial Surgery? J Oral Maxillofac Surg. 2022; 81: 8-16. 
9. Tang Y, Yang X, Yu Y, Shu H, Xu J, Li R, Zou X, Yuan S, Shang Y. Remimazolam versus traditional sedatives for procedural sedation: a systematic review and meta-analysis of efficacy and safety outcomes. Minerva Anestesiol. 2022; 88: 939-949. 
10. Paion. Paion launches Byfavo® (Remimazolam) in the UK for procedural sedation. 2021. Available from: https://www.paion.com/newsdetails/paion-launches-byfavo-r-remimazolam-in-the-uk-for-procedural-sedation/?cHash=04b6c8 adc0779e2e5dc273936a459a6d [Accessed 27 November 2022]. 
11. Scottish Medicines Consortium. Remimazolam 20mg powder for solution for injection (Byfavo®). Healthcare Improvement Scotland. 2022. Available from: https://www.scottishmedicines.org.uk/media/7040/remimazolam-byfavo-final-july-2022-for-website.pdf. 
12. Oka S, Satomi H, Sekino R, Taguchi K, Kajiwara M, Oi Y, Kobayashi R. Sedation outcomes for remimazolam, a new benzodiazepine. J Oral Sci. 2021; 63: 209-211. 
13. Jhuang B, Yeh B, Huang Y, Lai P. Efficacy and Safety of Remimazolam for Procedural Sedation: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis. Front Med. 2021; 8: 641866. 
14. Ul-Haque I, Shaikh T G, Ahmed S H, Waseem S, Qadir N A, Bin Arif T, Haque S U. Efficacy of Remimazolam for Procedural Sedation in American Society of Anesthesiologists (ASA) I to IV Patients Undergoing Colonoscopy: A Systematic Review and Meta-Analysis. Cureus. 2022; 14: e22881. 
15. Zhang L, Li C, Zhao C, You Y, Xu J. The comparison of remimazolam and midazolam for the sedation of gastrointestinal endoscopy: a meta-analysis of randomized controlled studies. Afr Health Sci. 2022; 22: 384-391. 
16. Zhu X, Wang H, Yuan S, Li Y, Jia Y, Zhang Z, Yan F, Wang Z. Efficacy and Safety of Remimazolam in Endoscopic Sedation—A Systematic Review and Meta-Analysis. Front Med. 2021: 65504. 
17. Borkett K M, Riff D S, Schwartz H I, Winkle P J, Pambianco D J, Lees J P, Wilhelm-Ogunbiyi K. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg. 2015; 120: 771-780. 
18. Pambianco D J, Borkett K M, Riff D S, Winkle P J, Schwartz H I, Melson T I, Wilhelm-Ogunbiyi K. A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2016; 83: 984-99. 

Enhancing experience of dental procedures under inhalation sedation with relaxing music: an overview to explore the potential

F. Rodrigues* BSc (Hons), BDS
Dental Core Trainee, London North West University Healthcare NHS Trust, Oral & Maxillofacial Surgery Department, Northwick Park Hospital Block L1, Level 4, Watford Rd, Harrow HA1 3UJ
*Correspondence to: Dr Francesca Rodrigues
Email: francesca.rodrigues@nhs.net
Rodrigues F. Enhancing experience of dental procedures under inhalation sedation with relaxing music: an overview to explore the potential. SAAD Dig. 2024: 40(II): 103-104

Abstract

Aims

This review will explore how relaxing music can be harnessed to positively impact the delivery of inhalation sedation for anxious dental patients.

Method

The literature was reviewed by searching electronic databases, excluding research prior to the year 2000. Data extraction involved identification of varying parameters of music (tempo, amplitude and systems of delivery) and how this impacts psychophysiology (mood, heart rate, blood pressure). Additionally, systematic reviews assessing the combined effect of music within sedation settings were also included.

Results

Research supports that patients who listen to relaxing music, while undergoing dental procedures under inhalation sedation, may have an improved experience. Some research also highlights improvements in vital signs associated with listening to music during surgery, especially for anxious patients.

Conclusion

Improvement of patient experiences of dental procedures under inhalation sedation may be possible by utilising relaxing music to promote a relaxed state.

Introduction

Dental procedures can be an unnerving combination of sensations: unsettling sounds, unpleasant flavours and application of tools that appear intimidating. From the patient’s perspective, the dental environment may be perceived as a frightening place synonymous with pain and anxiety. Sedation techniques offer a gateway for dentally anxious patients to access dental services. Inhalation sedation (IHS) is one method of conscious sedation that is relatively safe and effective. However, this form of sedation can be further improved with distraction techniques such as hypnosis and use of relaxing visual projections. The use of relaxing music has potential to be an especially effective distraction technique.

Background

Music can be emotionally polarising, eliciting moods of relaxation, happiness or even melancholy. A comprehensive review detailed the neurochemical reactions that occur when listening to music. Notably, there is a correlation between listening to low-frequency music and reduced levels of cortisol, a hormone that is typically associated with stress. Other physiological indicators of relaxation can also be observed, including lowered heart rate and respiration.¹ This rhythmic calibration of physiological parameters with appropriately selected music may significantly enhance the experience for patients receiving dental treatment under IHS.

For patients who have been appropriately selected and consented for IHS, it is important to ensure their experience is a positive one. An estimated 36% of the UK population has dental anxiety, some of whom may only accept treatment under sedation while others may completely avoid visiting the dentist.² Therefore, every effort should be made to optimise a relaxed state to avoid further intensifying a patient’s dental anxiety and to prevent the need for more consequential forms of sedation like general anaesthesia. IHS involves inhalation of nitrous oxide (N₂O) to achieve relative analgesia. Though IHS alone can induce anxiolytic effects, distraction techniques are frequently used to enhance sedation in the conscious patient.

The synergistic pairing of relaxing music with IHS benefits both operator and patient. Among the variety of distraction techniques that can be honed by operators, playing relaxing music is a straightforward yet effective means of maintaining relaxation during IHS. Thus, valuable information may be derived from exploring how musical parameters can be adjusted to benefit patients.

Music Selection

Music has many different genres and taste can be incredibly subjective. Perhaps the most taxing decision, after choosing to use background music, is what type of music to use. More specifically, questions about musical parameters may also arise, including genre, amplitude and use of lyrical or instrumental music. It seems logical to select any music that is considered relaxing. However, this encompasses many different genres such as jazz, classical and nature sounds. Being able to characterise the associated parameters of relaxing music can help with its selection.

One study investigated self-reported preferences for ‘softer’ amplitudes of music to promote a relaxed state, whereby loudness ideally does not exceed 70 decibels.³ Thoughtful consideration of amplitude for patients listening to music on personal devices is especially important for maintaining clear patient and dentist communication during procedures. For example, establishing the appropriate volume of music prior to starting a procedure, to check whether the patient can still hear the operator’s commands while listening to music on their personal device. A systematic review further attempts to define relaxing music, suggesting that non- lyrical music, with a slow tempo ranging between 60 to 80 beats per minute, is significant in pain management.⁴ Although the operator can play music that meets a relaxing standard, it is recommended that patients choose their own relaxing music to encourage their sense of autonomy.¹

Whether patients listen to relaxing music on a speaker or through personal devices, clear beneficial outcomes have been observed in patients. A systematic review highlights a reduction in pain and anxiety across many studies, including patients who listen to relaxing music before, during or after different surgical procedures. Additionally, 27% of studies which analysed vital signs, reported significantly reduced blood pressure and heart rate.⁵ The postulated mechanism of action underlying these responses is described in an article highlighting inhibition of sympathetic activity while the limbic system integrates auditory processing along with other environmental stimuli. Interestingly, a phenomenon known as entrainment can facilitate a relaxed state by synchronising parasympathetic activity with musical rhythms, as a result of upstream thalamic processing.6 Combined with the central nervous system depression that occurs during IHS, relaxing music can adjunctively evoke powerful anxiolytic and analgesic effects.

Patient factors and additional considerations

Relaxing music offers simplicity and wide-ranging benefits as a distraction technique. However, it is important to be considerate of patient suitability and preferences. Some patients may opt for silence while others may wish to consider alternative distraction techniques. A skilled operator may incorporate multiple distraction techniques or may not require any at all. In every case, it is paramount to be supportive and flexible so that the patient has a comfortable IHS experience.

A significant proportion of dental patients undergoing IHS are paediatric. A systematic review supports the use of relaxing music for adult patients, however, for paediatric patients the results are inconclusive.⁷ From a behaviour and developmental perspective, it is reasonable to use alternative methods in young children, perhaps focused more on visual stimuli, which was highly favoured by paediatric patients in one study.⁸

Medical history considerations may also present challenges within the sedation aspect of IHS, which render the use of music negligible. In particular, it may be difficult to achieve adequate levels of sedation in patients with psychological health struggles, such as bipolar disorder or more moderate levels of anxiety. In these cases, communication and a good understanding of the patient’s condition are likely to be more helpful than music.

If music is a chosen distraction technique, it would be interesting to consider additional variables for investigation. For example, quantifying how music may affect N₂O titration; whether playing music for a certain length of time influences sedation depth; or if there is a discrepancy between how music affects males and females. This information could serve to refine how music is delivered in a dental context with IHS.

Conclusion

Music can be a helpful supplement when used in conjunction with effectively delivered IHS. Provided that the patient is comfortable with music during IHS, it is an easy and likely harmless option that should be explored as an effective distraction technique. Improving the patient’s experience of dentistry under IHS should be the main focus, with relaxing music as a simple solution to address this. However, music is one of many options and does not substitute good communication skills and empathy. Therefore, patients listening to relaxing music under IHS holds exciting potential to optimise a patient’s experience of dentistry.

Conflicts of Interest

None

Acknowledgements

I wish to thank Community Dental Services CIC where my training in inhalation sedation allowed me to explore the benefits of music as an adjunct to patient care. 

References

1. Chanda M L, Levitin D J. The neurochemistry of music. Trends in Cognitive Sciences. 2013 Apr;17:179–93. doi:10.1016/j.tics.2013.02.007

2. Steele J, O’Sullivan I. Adult Dental Health Survey: Oral Health in the United Kingdom 2009 London: The Stationery Office; 2011.

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4. Martin-Saavedra J S, Vergara-Mendez L D, Pradilla I, Vélez-van-Meerbeke A, Talero-Gutiérrez C. Standardizing music characteristics for the management of pain: A systematic review and meta-analysis of clinical trials. Complementary Therapies in Medicine. 2018;41: 81–9. doi:10.1016/j.ctim.2018.07.008

5. Nilsson U. The anxiety- and pain-reducing effects of music interventions: A systematic review. AORN Journal. 2008;87: 780–807. doi:10.1016/j.aorn.2007.09.013

6. Krout R E. Music listening to facilitate relaxation and promote wellness: Integrated aspects of our neurophysiological responses to music. The Arts in Psychotherapy. 2007;34: 134–41. doi:10.1016/j.aip.2006.11.001

7. Moola S, Pearson A, Hagger C. Effectiveness of music interventions on dental anxiety in paediatric and adult patients: A systematic review. JBI Database of Systematic Reviews and Implementation Reports. 2011;9: 588–630. doi:10.11124/01938924-201109180-00001

8. Davies E B, Buchanan H. An exploratory study investigating children’s perceptions of dental behavioural management techniques. Int J Paed Dent. 2013; 23: 297–309. doi:10.1111/ipd.12007

Please click on the tables and figures to enlarge

Exploring the environmental impact of the NHS dental service with a focus on conscious sedation and anaesthesia

B. Revert*
Speciality Doctor in Restorative Dentistry, Croydon University Hospital, 530 London Rd, Thornton Heath CR7 7YE
*Correspondence to: Dr Bethany Revert
Email: Bethany.revert@nhs.net
Revert B. Exploring the environmental impact of the NHS dental service with a focus on conscious sedation and anaesthesia. SAAD Dig. 2024: 40(II): 105-109

Abstract

Understanding the extent to which our health service contributes to the climate crisis is vital. All areas of healthcare are currently environmentally unsustainable due to being highly resource intensive. Undertaking dental treatment in both primary and secondary care contributes to the carbon footprint of our health service. This comprises the use of pharmacological intervention with both conscious sedation and general anaesthesia. This paper aims to analyse how we can continue excellent patient care while being more sustainably aware.

Introduction

Over the years, the narrative surrounding climate change has evolved and is becoming widely viewed as the biggest global health threat of the 21st century.¹ The principles of beneficence and non-maleficence which underpin dental practice raise an important question: ‘How can we provide dental care without harming the environment and in turn protect our patients?’

Emerging studies have identified an increase in mental ill health and anxiety since the COVID-19 pandemic.² The need for anxiety management within both primary and secondary care settings has never been more essential but the additional requirements of these patients will increase the carbon footprint of our services. To fully comprehend this impact, evaluation of our healthcare service delivery becomes paramount.

One of the essentials of environmental impact analysis is the quantification of the greenhouse gases. Greenhouse gases are grouped into a common unit called carbon dioxide equivalent (CO₂e).3 In 2008, the UK Climate Change Act set out a legal framework to cut gas emissions to 100% below 1990 levels by 2050. This highlighted the need for collaborative effort to ensure positive and productive change to reduce the environmental footprint. High figures for CO₂e and waste generation suggest that healthcare delivery is currently not environmentally, socially or financially sustainable.⁴ To tackle this, the NHS published a report in 2020 providing an updated account of the latest NHS carbon footprint. This report includes an ambition to achieve a ‘net zero’ health service and the initial aim is to reduce greenhouse gas emissions by 80% before 2040. Not only is this an enormous target, but the NHS was the first health service in the world to propose this.⁵

Most emissions from the NHS fall into three main categories: direct emissions from on-site healthcare, indirect emissions from the generation of purchased energy and indirect emissions due to producing and transporting goods. Areas of healthcare that fall outside of these main categories include staff and patient travel and the carbon footprint of prescribed medication.⁵

Accurately quantifying the carbon footprint of dental services is challenging. However, it is suggested that 3% of the overall carbon footprint of the NHS in England is due to dental services, which equates to a total carbon footprint of around 670,000 people.^6,7

Within the 2021 Lancet report on health and climate change, it was stated that current global commitments are insufficient. They estimated that with no changes we will see a 2.4°C global temperature increase by the end of the century. If the global temperature were to rise above 2°C this would lead to worldwide consequences, including death due to intense heat, alterations in food availability and increased infectious disease transmission.⁸

Dentistry as a whole

With the joint pressure of the NHS Net Zero target and the Climate Change Act, dentistry within the UK has had to further investigate its role in reducing our carbon footprint. In January 2023, clinical guidelines for environmental sustainability in dentistry were published. These were the first dentistry-focused guidelines relating to improving the sustainability of our profession. The overall aim of these guidelines is to raise awareness, provide needed direction to the dental cohort and to reduce carbon emissions.⁹ These guidelines incorporate the 2030 United Nations (UN) sustainable development goals, which emphasise the need to ‘take urgent action to combat climate change’.¹⁰

Within the clinical guidelines are seven major domains, which can be seen below in Table 1. Each of these breaks down the multiple facets that lead to the overall carbon footprint within dentistry in England. These guidelines are relevant for individual practitioners, governments and public health professionals. Domain two directly mentions the reduction of anaesthetic gases for dental procedures.⁹

Another useful tool is the Campaign for Greener Healthcare’s four principles. These include underpinning sustainable practice, including disease prevention and health promotion, patient education and empowerment, lean service delivery and preferential use of treatment with a lower environmental impact.¹¹ These areas of improvement can be seen illustrated in the driver diagram in Figure 1.

To be able to reduce carbon intensity, we must investigate which procedures have the largest carbon footprint. Examinations, scale and polishes, radiographs and fluoride varnish applications have the lowest carbon footprint due to the minimal materials used. However, due to the extensive number of examinations required, it still equates to a large proportion of our carbon footprint. Procedures with higher carbon footprints come from more extensive procedures, which either require increased material use or multiple appointments. In clinical situations where conscious sedation or general anaesthesia (GA) is required, an increased carbon footprint occurs due to the addition of more staff and the use of N₂O or other gases.⁷

The most used dental materials are amalgam and composite. Excluding the presence of mercury within amalgam, the comparative carbon footprint of these two materials is unknown. In addition, the environmental breakdown of these products is not understood. Motivation for these analyses to take place is required, allowing the profession and public to make an informed material choice. However, it is known that dental mercury equates to 3 - 4% of terrestrial mercury. In total 75 metric tonnes of amalgam are used per year in the EU alone.³ The Minamata Convention has highlighted the need to reduce mercury use across the globe, which has directly impacted usage in dentistry. Conversely, in clinical situations where moisture control is difficult to achieve or when applying the most affordable option, amalgam is still a material of choice.¹²

Although looking at dental procedures and materials is important, we know that the highest proportion of emissions due to dentistry in the UK came from travel, procurement, energy and N₂O.⁷ Therefore, further analysis of indirect carbon usage in dentistry needs to be completed. Approximately 3.5% of all road travel in England is due to healthcare-related excursions.⁵ Despite it being an indirect cause, encouraging staff and patients to switch to lower carbon footprint transport options is essential. Alongside this, we can evaluate the patient pathway by highlighting access to dental services. NHS England is required to ensure it commissions services in areas that are easily accessible for patients to travel to and from, as well as being available to all.⁷ Timely diagnosis and treatment, can minimise the need for further invasive treatment. There is a delicate undertaking with this, as more practices also add to increased output and a higher carbon footprint.

In the same way that access is important, we must also explore how an integrated care model could improve our carbon footprint.¹³ Certain areas of the UK don’t have facilities for dental treatment under sedation, therefore in some circumstances, GA may be the only option for these patients. GA requires more staff and increased use of ozone-depleting gases. Therefore, if it was possible to design and deliver more efficient, effective patient pathways we could reduce the need for unnecessary high carbon footprint procedures. 

To tackle both travel and the use of resources, one suggestion to make dentistry more sustainable is to complete as much treatment in one session as possible. However, when pharmacological intervention is required due to dental anxiety or medical history, there is a limiting factor of drug working time. Whilst this may be more achievable under GA, this is not necessarily the most practical or safe option due to theatre availability and the risks of anaesthesia. Furthermore, GA itself carries a heavy carbon burden through travel, staffing, enormous waste generation and energy consumption.¹⁴

Before using pharmacological interventions, all steps should be taken to try the least invasive option. This can include acclimatisation of dental treatment. If this is not possible due to severe anxiety, an appropriate pre-assessment should be completed. This includes an anxiety assessment tool, such as the Modified Dental Anxiety Scale.¹⁵ Patients are required to reach a certain threshold to qualify for sedation techniques under our current health service. This is a useful tool in ensuring we are only undertaking appropriate treatment measures. To reduce the environmental impact of sedation even further, reducing the prevalence of dental anxiety is required. Ideally, the use of psychotherapeutic interventions should be first-line management before pharmacological agents. However, in patients with severe anxiety, a combination of both may be required. The use of these additional psychological interventions could lead to a patient being able to undergo dental treatment without conscious sedation thereby improving patient outcomes, whilst reducing the environmental footprint as a side effect.¹⁶

Inhalation sedation with N₂O

In current dental practice inhalation sedation (IHS) is undertaken inboth primary and secondary care settings. Indications for its use include dental anxiety, needle-phobia, traumatic or prolonged dental procedures, medical conditions aggravated by stress and patients who require sedation and who have no escort.¹⁷

In dentistry, we regularly use nitrous oxide (N2O) for conscious sedation which is a potent greenhouse gas. The global warming potential (GWP) of N₂O is 298 times higher than CO₂. Despite it having a shorter life cycle than CO₂, the damage it causes within the same timeframe is much increased.¹⁸ The N₂O released during the sedation of an estimated 63,749 patients, produced almost 1% of the total carbon footprint of NHS dental services in England.⁸

In dental practice, the exhaled gas is removed using a scavenging system. This delivers the exhaled vapours out of the clinical environment, which aims to reduce the occupational exposure of staff. It is common practice to also ensure adequate fitting of the nasal hood to ensure no excess N₂O is released into the local environment.⁷ However, N₂O does not undergo any form of metabolic change within the human body, and therefore any exhaled gas will pollute the planet.³ Suitable alternatives to releasing this exhaled N₂O are being explored. Technological advances are being trialled, mainly within theatre settings in the UK, though European counterparts have already been using N₂O denaturing devices for several years.

Despite N₂O’s high GWP the use of IHS is seen as a less invasive option compared to intravenous sedation (IVS) or GA. Therefore, there is a delicate balance between minimising the use of IHS while still offering the least invasive treatment option.⁷

General anaesthesia using ozone-depleting gases

It has been estimated that an average of 163 litres of N2O is used during one procedure of GA per patient episode. This does not consider the carbon footprint of the travel and procurement process.³ The use of inhalational anaesthetic agents equates to around 5% of the total carbon footprint of acute NHS trusts. It is therefore unsurprising that when N₂O is used, it equates to the biggest component of the carbon footprint of GA.¹⁹

Steps can be taken to reduce the amount of N₂O used during GA. These include ensuring well-fitting masks, flushing of the system correctly, turning off valves as soon as no longer required and ensuring there are no leaks within the system.³

The use of catalytic splitting could cut over one-third of NHS anaesthetic emissions.⁵ This process requires an external unit to heat the N₂O to 400°C, producing both oxygen and nitrogen as by-products. This technology has been successfully deployed in Sweden.²⁰ Currently this is more readily used for GA due to the ease of installing one large unit for multiple theatres. However, we are starting to see the use of smaller units in dental settings for single rooms. For example, Medclair has produced a mobile destruction unit which reduces over 99% of N₂O to its harmless byproducts.²¹ This is currently being piloted in England to investigate the ease of use for dental services. Promising results have been seen with this technology, for example a 52% decrease in N₂O emissions from birthing units in Stockholm.²⁰

As healthcare professionals, we already aim to try and avoid the need for GA due to additional medical risks. The knowledge of the increased environmental impact of GA allows us to further warrant the use of less invasive means. Due to the recent COVID-19 pandemic, waiting lists for GA suites are high and ever-growing,²² therefore further funding is required to allow the implementation of such technologies to offset the high use of theatres.

Sedation using midazolam and alternatives

Where IHS is contraindicated or anxiety management is unsuccessful, alternative pharmacological interventions can be applied. One of the most common options is the use of midazolam. The route of delivery for this drug can be either intranasal, oral or intravenous. Generally intranasal and oral routes are used pre-operatively before completing cannulation for intravenous midazolam use.²³

Compared to non-sedation related practices, we can be certain the carbon footprint of the additional drug and environmental impact for disposal will be greater. However, comparing IVS directly to inhalation practice is more complex. It has been suggested that total intravenous anaesthesia could have a lower environmental impact, it also reduces the risk of occupational exposure and pollution to the atmosphere. Despite this, correct disposal of all IV agents should be followed to reduce environmental contamination.²⁴ This evidence could be applied to IVS, however, within dentistry this is seen as the more invasive option over IHS. This is due to the prolonged recovery period, the requirement for an escort and the additional monitoring required. Therefore, despite the possible reduced carbon footprint, we are unable to ethically suggest the use of intravenous midazolam over IHS. 

In certain situations, for example severe dental anxiety or low co-operation, midazolam can be administered alongside other agents or alternative agents used entirely. These include fentanyl, propofol, ketamine and sevoflurane gas.²³ Sevoflurane is less environmentally damaging compared to N₂O and it is comparable for sedation, but further research and adaptation to dentistry is required before routine use.²⁵ 

Like midazolam there is limited evidence on the environmental impact of fentanyl, propofol and ketamine use for dentistry. These drugs are used as advanced techniques and are likely occurring in small numbers.²³ Further research is required to fully understand the breakdown of these products in the ecosystem.

Clinician education

A recent study showed that only 9% of students believed they had formal teaching on sustainability despite 97.3% of students believing the profession should be more actively engaged.²⁶

For many years, the General Medical Council has implemented specific learning outcomes for undergraduates, focusing on sustainable healthcare.²⁷ This was an early sign that interest in the link between our medical practices and the environment was increasing. In November 2023, the General Dental Council launched the new framework for dental professional education, which will be implemented in undergraduate programmes from 2025. This framework includes a sub-domain called social accountability, requiring formal teaching on sustainable oral health and the environmental impacts of common treatment methods.²⁸ This change allows us to engage the future generation of healthcare professionals to enable them to aim for more sustainable practice.

For our postgraduate colleagues, an introductory course on sustainability is available free for all on Health Education England’s e-Learning for Health platform.^29,30 Training courses such as this require promotion by local trusts to ensure the workforce is aware of their existence.

Patient education

A downstream, preventative approach to oral health care will have the biggest impact on reducing the need for dental treatment.³¹ Preventative items such as fluoride toothpaste, fluoride varnish and fissure sealants can reduce the likelihood of large areas of dental caries and therefore restorative treatment.³¹ Education for care staff or carers can add another layer to the preventative approach. Improving education and knowledge can reduce an individual's likelihood of poor oral health. We must ensure we are following the Delivering better oral health toolkit to assess the risk status of our patients and giving them tailored advice and education.³¹

COVID-19

During the COVID-19 pandemic, phone triage became the only option for patients who were experiencing dental pain and swelling, and many patients were left without access to treatment.³² Despite national restrictions being lifted there has been a continuation of this practice with some using an initial video assessment before treatment.³³ This is a useful tool to mitigate the need for travel for initial discussions or where a clinical exam is not required. This is useful for patients with access or transport difficulties. The long-term implementation of virtual assessments and telephone consultations could help reduce patient travel.

Conclusion

The long-term sustainability of our health service relies on the collaboration and motivation of all specialities. Successfully treating patients with conscious sedation or GA is a clinical necessity and so further research is required to allow us to aim for a more environmentally sustainable practice. Indirect causes of carbon usage such as travel, procurement and wastage require further alteration and motivation from the workforce at all levels. The use of N₂O is concerning, although clinically necessary for anxiety management, and advances in catalytic cracking are likely to have the biggest impact on reducing the damage caused by N₂O. Downstream prevention of both dental disease and dental anxiety is vital to help reduce the need for treatment, this practice can only be successful with patient and clinician education. In conclusion, we can shape a more sustainable and safe future by collaboratively working together.

Declaration of Interest

 There are no conflicts of interest.

Acknowledgements

I would like to acknowledge Dr Zahra Shehabi, for inspiring me to become involved in this area of dentistry, as well as her continued support in my career.

References

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3. Martin N, Sheppard M, Gorasia G P, Arora P, Cooper M, Mulligan S. Awareness and barriers to sustainability in dentistry: A scoping review. J Dent 2021; 112: 103735.

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6. Public Health England. Carbon modelling within dentistry: towards a sustainable future. Crown: London. 2018. Online information available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/724777/Carbon_modelling_within_dentistry.pdf (accessed March 2024).

7. Duane B, Lee M B, White S, Stancliffe R, Steinbach I. An estimated carbon footprint of NHS primary dental care within England. How can dentistry be more environmentally stable? Br Den J 2017; 223: 589-593.

8. Romanello M., McGushin A, Napoli D et al. The 2021 report of the Lancet Countdown on health and climate change: code red for a healthy future. Lancet 2021; 398: 1619-1662.

9. Duane B, Fennell-Wells A. 2023. Clinical guidelines for environmental sustainability in dentistry.

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11. Mortimer F. The sustainable physician. Clin Med (London) 2010; 10: 110-1

12. Fisher J, Varenne B, Narvaez D, Vickers C. The Minamata Convention and the phase down of dental amalgam. Bulletin of the World Health Organization. 2018; 96: 436–438.

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16. Appukuttan, D. Strategies to manage patients with dental anxiety and dental phobia: literature review. Clin Cosmet Investig Dent 2016; 8: 35–50.

17. Coulthard P. The indicator of sedation need (IOSN). Dent Update 2013; 40: 466–471.

18. Erisman J W, Galloway J, Seitzinger S, Bleeker A, Butterback-Bahl K. Reactive nitrogen in the environment and its effect on climate change. Curr Opin Environ Sustain 2011; 3; 81-290.

19. Shelton C L, McBain S C, Mortimer F, White S M. A new role for anaesthetists in environmentally sustainable healthcare. Anaesthesia 2019; 74(9): 1091–1094.

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24. Varughese S, Ahmed R. Environmental and Occupational Considerations of Anesthesia: A Narrative Review and Update. Anesth Analg 2021; 133: 826-835.

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Impact of anxiety and midazolam on physiological control of arterial blood pressure (BP) and heart rate (HR)

S. Rehman* BDS, MFDS(RCS Ed) MSc (Pub Health) DipConSed
Dental Core Trainee in OMFS, Gloucester Royal Hospital, NHS Foundation Trust, Great Western Road Gloucester England GL1 3LZ
*Correspondence to: Dr Sooda Rehman
Email: drsoodsrehman@hotmail.com
Rehman S. Impact of anxiety and midazolam on physiological control of arterial blood pressure (BP) and heart rate (HR) SAAD Dig. 2024: 40(II): 110-112

Abstract

Knowledge of human physiology and the properties of the sedative agents used in the provision of dental treatment with conscious sedation is vital. The most commonly used sedative agent for intravenous (IV) sedation is midazolam which belongs to the benzodiazepine group of drugs. Both anxiety and midazolam affect the heart rate. However, long-term anxiety could result in hypertension. Soon after its induction midazolam affects the heart rate by changing the autonomic nervous system control of heart function as well as baroreflexes. It is worth noting that heart rate during sedation with midazolam will not reach the base level, whereas blood pressure drop could be uncertain.

Introduction

An appropriate medical history, social history and physical assessment is key to ensure an appropriate case selection for conscious sedation. Therefore, knowledge of the pharmacodynamics and pharmacokinetics of the drugs that are used in sedation is essential along with their interactions with other drugs which the patient may take routinely for any existing medical conditions. According to the Adult Dental Health Survey 2009, anxiety is prevalent in over a one third of the United Kingdom’s population.¹ Conscious sedation plays a pivotal role in the provision of dental treatment for patients who suffer from dental anxiety and / or dental phobia. The most commonly used sedative agents in dentistry are midazolam and nitrous oxide. Midazolam belongs to the benzodiazepine group of drugs. Like all other sedative agents midazolam depresses consciousness as well as cardiovascular function. In this paper the impact of anxiety and midazolam on physiological control of arterial blood pressure and heart rate will be discussed.

Heart rate

The heart is an organ which pumps oxygenated blood to the different parts of the body and deoxygenated blood back to the lungs. To achieve this function the heart has to contract continuously in a co-ordinated fashion.²

The number of times a heart beats in a minute is defined as the heart rate (HR).³ Normally, a heart beats around 60 to 80 times a minute.³ Major factors which can modify the HR are as follows.³

Autonomic tone

The autonomic nervous system (ANS), which comprises the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS), provides the innervation to the heart. The autonomic tone is generated through the balance between the inputs from SNS and PSN. The parasympathetic input to sino-atrial node (SAN) is dominant at rest.³

Response to pain and anxiety

The body’s response to fear, anxiety or stress triggers SNS that innervates the atrioventricular node (AVN) and SAN and releases noradrenaline, resulting in increased HR and force of contraction.

Baroreceptor mechanism, chemoreceptors and circulating hormones are discussed later in the section entitled ‘Physiological Control of Arterial blood pressure and HR’.

Cardiac output

The total volume of blood in an average adult is 5 to 6 litres.³ The volume of blood pumped by the heart in a minute is called cardiac output (CO) which is the product of the HR and stroke volume (SV).⁴ SV is defined as the amount of blood pumped by the left ventricle in a single contraction.⁵ A resting CO in an average adult is 5.5l/min.³

Peripheral resistance

To pump the blood through the circulatory system, resistance to blood flow must be overcome. The resistance generated through the systemic vascular system is known as total peripheral resistance (PR).⁶

The SNS controls the radius of the blood vessel, and any changes in the radius can cause a significant change in the blood pressure (BP) by altering the PR. Similarly, factors which affect the blood’s viscosity, eg temperature, haematocrit value and plasma protein concentration, also affect the BP by increasing or decreasing the PR.

Arterial blood pressure

‘Arterial blood pressure (ABP) is determined by the volume ejected by the heart into the arteries, the elastance of the walls of the arteries, and the rate at which the blood flows out of the arteries.’ ⁷ ABP can also be defined as a product of cardiac output and peripheral resistance.

Physiological control of arterial blood pressure and heart rate

The ABP is regulated by the following major mechanisms:

Baroreceptors

The carotid sinus and aortic arch have specialised stretch receptors called baroreceptors. These receptors detect changes in the BP and send impulses to the vasomotor centre (VMC) to regulate the BP by increasing or decreasing the HR and CO.⁵

Chemoreceptor reflex

As a result of tissue ischemia, peripheral chemoreceptors are stimulated which stimulates VMC and results in an increase in HR, BP and depth of respiration.⁵

Central nervous system (CNS) ischaemic response

CNS response is initiated when BP falls below 50mmHg and results in stimulation of the VMC which stimulates SNS to increase HR and BP to maintain normal function.⁵

Renal regulation of BP

The kidneys regulate arterial blood pressure through direct mechanism (ie pressure diuresis) and the pressure natriuresis and the indirect mechanism (ie hormonal control). Major hormones are as follows:⁵

• Renin angiotensin system (RAS): provides the long-term control of ABP. Through this system, the kidneys compensate for the decrease in ABP by the release of a endogenous vasoconstrictor (ie angiotensin II) that raises the ABP.
• Aldosterone: is a steroid hormone released from the adrenal cortex by angiotensin II (ATII) which increases the sodium resorption and increases the excretion of potassium in a distal convoluted tubule of the kidney resulting in an increase of BP. ATII also increases PR by vasoconstriction of the arterioles to increase BP.
• Antidiuretic hormone (ADH): ATII also causes the release of ADH (vasopressin) from the posterior pituitary which increases the blood volume by reabsorption of water from the kidneys which increases the BP.
• Epinephrine and norepinephrine: these hormones are released by the adrenal medulla under stress, pain and anxiety etc as a part of the ‘fight or flight’ mechanism. They raise the BP by increasing the HR and contractility of the heart muscles while causing vasoconstriction of the arteries and veins.

Thyroxine

Thyroxin is a hormone produced by the thyroid gland which increases the HR and CO by acting on beta 1 receptors and potentiates the effect of epinephrine. Other hormones like atrial-natriuretic peptide and brain natriuretic peptide also have an impact in the regulation of HR and BP.²

Effect of an anxiety / phobia on blood pressure and heart rate

Some patients are not able to accept dental treatment due to their high level of anxiety or phobia. Anxiety and fear stimulate the SNS, resulting in an increase of the circulating catecholamines and an increase in the HR and BP.

Anxiety is considered to have a short and long-term effect on the BP. In the short term it can increase the BP and ‘white coat syndrome’ is a good example of this.⁸ The long-term effect of anxiety can result in decreased vascular variability resulting in an increased PR which can eventually cause hypertension.⁸

Generalised anxiety is often associated with an unhealthy lifestyle which, in turn, could cause an increased risk of hypertension. Higher risk of death is noted due to ischaemic heart disease among patients who have phobic anxiety disorder.⁹

Effect of midazolam on blood pressure and heart rate

Midazolam is short acting benzodiazepine which has been used in dentistry since the 1980s to provide sedation. Administering a sedative dose of benzodiazepine will result in approximately a 5 to 10% reduction in BP. Midazolam is known to affect BP and HR by changing the ANS control of the heart function as well as baroreflexes.¹⁰

Midazolam has a depressant effect on the sympathetic response that produces a small decrease of the ABP immediately after induction by decreasing PR, myocardium contractility and venous return. However, this is promptly compensated by the baroreceptor reflex and the HR is then increased so as the myocardium contractility to maintain the CO.

This is particularly relevant as the HR will not drop to a true resting rate during sedation, a less experienced seditionist may confuse this with under-sedation. It is uncertain to what extend the fall in BP is a result of the relief of anxiety, or the action of the drug itself.

This hypotensive effect is of clinical significance amongst elderly patients or patients with compromised cardiovascular disease. Midazolam used in high doses can cause deep sedation and the direct inhibition of the cardiovascular system (CVS).¹¹ However, in combination with other drugs in low dose it can cause CVS stability.¹²

Discussion

The person with systolic and diastolic blood pressure below 140/90mmHg is classed as normotensive, whereas sustained increase of systolic blood pressure measurement of 140mmHg with, or without, an increase of diastolic blood pressure above 90mmHg is defined as having clinical hypertension.¹³ According to the Office for National Statistics’ 2023 report based on the Health Survey for England for 2015 – 2019, 32% of the United Kingdom’s population living in private households suffered from hypertension, with 29% having undiagnosed hypertension.¹⁴ 

There was reported to be a higher incidence of undiagnosed hypertension in the population aged 16 to 34 compared to the population aged over 75.¹⁴ The increased prevalence of hypertension has been associated with increased age and high BMI along with other factors like ethnicity and region etc.¹⁴ These statistics highlight the importance of pre-assessment for conscious sedation provision in detecting any undiagnosed hypertension. This could lead to better outcomes for the patient in general as it can lead to a timely management of hypertension and its causes.¹⁵ The clinician needs to adopt a holistic approach throughout the patient’s journey from pre-assessment to recovery following a procedure under conscious sedation as multiple factors like ‘white coat syndrome’, the patient’s regular medication, anxiety, inadvertent introduction of adrenaline based local anaesthetic into a vein etc could potentiate the impact of midazolam on the cardiovascular system.

Conclusion

A sound knowledge of human physiology is imperative for the safe practice of conscious sedation as it allows the operator to understand the impact of sedative agents on blood pressure and heart rate. Recording of all the basic vital signs during pre- assessment is fundamental for the patient’s safety as it helps in appropriate case selection. Conscious sedation in dentistry is a safe alternative to general anaesthetic provided it is practised by a trained seditionist. Anxiety management during the provision of dental treatment can help to reduce the risks to cardiovascular function.

Acknowledgements

 Work was carried out as part of PG diploma in conscious sedation in King’s College London.

Conflicts of Interest

 There are no conflicts of interest.

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