Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Dr Mohan Z Mani,
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Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018

Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."

Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018

Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."

Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018

Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
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I wish JCDR a great success and I hope that journal will soar higher with the passing time."

Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
On Sep 2018

Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."

Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata

Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
On Aug 2018

Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".

Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
On Aug 2018

Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".

Dr. Mamta Gupta
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018

Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.

Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."

Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."

Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Original article / research
Year : 2021 | Month : August | Volume : 15 | Issue : 8 | Page : ZC38 - ZC42 Full Version

Comparison of Nitrous Oxide-Oxygen as Inhalation Agent, Midazolam, Ketamine alone and in Combination as Oral Sedative Agents for In-office Paediatric PatientsA Randomised Control Trial

Published: August 1, 2021 | DOI:
Monika Nagpal, Mohan Lal Khatri, Anil Gupta, Ankit Srivastava, Shalini Garg

1. Paediatric Dentist, Department of Paediatric and Preventive Dentistry, SGT University, New Delhi, Delhi, India. 2. Ex-Professor, Department of Anaesthesiology and Critical Care, SGT University, Gurgaon, Haryana, India. 3. Professor and Head, Department of Paediatric and Preventive Dentistry, SGT University, Gurgaon, Haryana, India. 4. Reader, Department of Paediatric and Preventive Dentistry, SGT University, Gurgaon, Haryana, India. 5. Professor, Department of Paediatric and Preventive Dentistry, SGT University, Gurgaon, Haryana, India.

Correspondence Address :
Monika Nagpal,
E-31-B, Vatika Apartments, Mayapuri, New Delhi-110064, India.


Introduction: In-office pharmacological sedation techniques are best applied to manage an extremely fearful preschooler, especially during primary dentition or a child’s early mixed dentition period. These should be used when non pharmacological behavioural management techniques fail either due to lack of communication or in children with special care needs.

Aim: To compare the efficacy of oral administrations of midazolam, ketamine, combination of midazolam-ketamine (M+K) and nitrous oxide-oxygen (N2O) inhalational sedation in achieving favorable behavioural outcome compared by using the Houpt scale in the treatment of anxious and uncooperative paediatric patients.

Materials and Methods: A randomised clinical trial was conducted in the Department of Paediatric and Preventive Dentistry, SGT University, Haryana, India between September 2018 to December 2019. The study included 100 anxious children (Venham’s picture scale) aged three to five years, who required procedures under local anaesthesia administration were divided into four groups using envelop method. Each group was given either oral midazolam (M) (0.3 mg/kg) or oral ketamine (K) (3 mg/kg) or oral combination of midazolam+ketamine (M+K) (0.3 mg/kg and 2 mg/kg) or inhalational nitrous oxide-oxygen (N2O). The behaviour response of the child was recorded using the Houpt scale. The oxygen saturation level and heart rate of each patient were also recorded before, after, and during the procedure. Adverse drug reactions post-treatment was also recorded. Analysis of Variance (ANOVA), Chi-square test and Mann-Whitney U test was used for statistical analysis.

Results: The study comprised of 100 anxious children (mean age was 4.1±0.5 years) requiring administration of local anaesthesia with intent to complete in-office treatment. Statistically, a significant difference was found among behaviour outcomes of four groups (p-value=0.047). Acceptable behaviour was seen best in K+M group (88%), followed by oral ketamine (K) (68%), N2O (59%), and oral midazolam (M) (52%). Adverse reactions were most commonly seen in the oral ketamine group.

Conclusion: Oral M+K combination group is significantly better than oral ketamine (K), oral midazolam (M) or N2O inhalation sedation to achieve the required behaviour for dental treatment in three to five years old patients.


Benzodiazepine, Conscious sedation, Inhalational sedation, Pharmacological behavioural management

Paediatric patients have dental anxiety, with a reported range of prevalence between 5-24% in various studies (1),(2),(3). Initially, non pharmacological behavioural management techniques were being used to achieve treatment goals. Management of fearful, anxious and specially-abled children many times need mild to moderate sedation in the dental office (4). Midazolam and ketamine are the most commonly used sedative agents to modify undesirable behaviour to complete short term in-office procedures under moderate sedationas compared to other oral sedatives (5),(6).

Midazolam is an imidazobenzodiazepine having a half-life of one two hours and rapid onset of action with a safe dose ranging from 0.2-0.5 mg/kg (7). It works as mild analgesic resulting from the central suppression of pain (8). Ketamine is fast acting sedative with wide margin of safety being a non narcotic, non barbiturate drug. This produces a unique combination of sedation, amnesia, and analgesia making this agent a choice for moderate sedation. Co-administration of these two drugs reduces the required dose of each by around 50%, managing the incidence and severity of side-effects related to both sedative agents (9),(10). The carefully titrated oral route has been proven to be an acceptable and familiar mode of drug administration (4),(5), comparable to the famous inhalational conscious sedation technique, which uses nitrous oxide-oxygen with oxygen. It is a colorless gas having faint, sweet smell. It acts by Central Nervous System (CNS) depression initiates euphoria, analgesia along with minor effect on the respiratory system (11). However, the best sedative outcome results due to superior efficacy as well as least side effects. To compare the efficacy of oral administrations of midazolam, ketamine, and combination of midazolam-ketamine with nitrous oxide-oxygen-(N2O) inhalational sedation in achieving favorable behavioural outcome compared by using the Houpt scale in the treatment of anxious and uncooperative pediatric patients.

Material and Methods

This randomised clinical trial was carried out in the Department of Paediatric and Preventive Dentistry, SGT University, Haryana, India between September 2018 to December 2019, comprising 100 anxious children between the age group of three-five years. The approval from the university ethical committee was taken before starting the study letter No.: SGTU/Exam./SCY_17-18/10621.

Sample size calculation: The sample size of the present study was calculated on basis of a pilot study done on 20 children. A sample included a total of 100 patients was deemed sufficient (Statistical power of 0.80 and a significance level of 0.05).

Sedation techniques used in the present study are routine pharmacological behaviour management procedures in paediatric dentistry. Written consent from parents of all patients was taken. Hundred children were equally divided into four groups (N=25) and were administered with either oral midazolam or oral ketamine or oral combination of midazolam+ketamine or inhalational N2O. Also, the subjects were divided into two groups based on age (based on communicative stages i.e., stage 3-4 and 4-5) for statistical purpose.

Inclusion criteria: Children who were anxious between the age group of three-five years, who have scored three or more according to Venham picture scale (12), who required procedures with local anaesthesia administration, falling under the group I and II of the American Society of Anesthesiologists (ASA) physical status classification (13) and whose parents provided with consent were included in study.

Exclusion criteria: Children falling under the ASA Group III, IV and V were excluded from the study.

Randomisation was done using 100 sealed envelopes divided equally among four agents to be used in the given study. The moderate sedation agent was picked by the parents/guardian after shuffling the envelopes. The appointment was given to children with recommended pre-sedation set of instructions along with to report empty stomach. This included nil per oral prior to three hours of appointment including liquids.

The selected children were divided equally into four groups according to the drug for sedation. Children requiring oral administration of the drugs, oral midazolam (0.3 mg/kg) (group M), oral Ketamine (3 mg/kg) (group K), and a combination of oral midazolam-ketamine (0.3 mg/kg and 2 mg/kg) (group K+M) were given 30 minutes prior to the procedure. Although, the literature states that the safest dose of midazolam ranges from 0.2-0.5 mg/kg (6) and for ketamine, it’s 3-10 mg/kg (4), but for the safety concern of paediatric patients authors used the minimal dose in this study, whereas, in the case of inhalational route administration of nitrous oxide-oxygen (group N2O) was initiated at the time of procedure (Table/Fig 1).

Syrup was prepared from the intravenous vials of midazolam and ketamine. According to the weight of the child, sedative drug was mixed with a flavored drink (Frooti™-Parle Agro India Pvt Ltd.,) and was given to the patient in order to mask the bitter taste of medicines.

The behaviour response of the child was recorded using the Houpt scale (Table/Fig 2) (14) after administration of local anaesthesia. This classification was grouped for statistical evaluation into two scales for better understanding:

(i) Non acceptable behaviour -Aborted (no treatment rendered), poor and fair behaviour.
(ii) Acceptable behaviour- Good, very good, and excellent behaviour was considered.

Authors further categorised the assessment of the intensity of behavioural response of sleep, movement, and crying as:

(i) Favorable (sleep score 1 and 2, movement score 3 and 4, crying score 3 and 4) and
(ii) Non-favorable (sleep score 3, movement score 1 and 2, crying score 1 and 2)

This method increases the possibility to detect minor changes in a child’s behaviour between the age groups of three to five years. The oxygen saturation level and heart rate of each patient was recorded before drug administration, during the procedure (at the time of local anaesthesia administration), and after the procedure using a pulse oximeter.

Any adverse drug reactions were recorded. The patient was discharged only after the normal oxygen saturation level and heart rate were achieved. Post sedation instructions were given to the patient regarding eating and drinking to begin by giving clear liquid such as clear juices, water, gelatin, popsicles, if your child does not vomit after 30 minutes, you may continue with solid foods. Single operator carried out the study and behaviour assessment to prevent bias.

Statistical Analysis

Statistical analysis was done using software from IBM Corporation, Statistical Package for the Social Sciences (SPSS) Inc., Chicago, IL, USA version 17.0 software package. The groups were compared using ANOVA, Chi-square test, and Mann-Whitney U test.


The study comprised of 100 anxious children (mean age: 4.1±0.5 years) requiring administration of local anaesthesia with intent to complete in-office treatment.

The difference between the male and female in the sample was not significant (p-value=0.376) (Table/Fig 3). Eight (32%) children from the nitrous oxide-oxygen sedation group were excluded because they didn’t accept the nasal mask and the sedative agent couldn’t be initiated. These children were treated under general anaesthesia.

Evaluation of the overall behaviour was carried out through Houpt behaviour rating scale (Table/Fig 4). Acceptable behaviour was seen best in the K+M group (88%) followed by ketamine (68%), nitrous oxide-oxygen (59%) and midazolam (52%). Statistically, a significant difference was found among behaviour outcomes of four groups using Chi-square test (p-value=0.047).

Intergroup comparison was done using the Mann-Whitney U test, a significant difference was seen only when combination (M+K) group was compared to other groups, no other intergroup comparison showed significant difference (Table/Fig 5).

Nitrous oxide-oxygen group was removed from the >3 to ≤4 (years) age group as there was only one patient left in that group (Table/Fig 6). For both age groups sleep scale with no loss of communication and movement along with no crying was the most favourable score observed in the K+M group in this group. Whereas, for age group >4 to ≤5 (years); the sleep scale was most favourable in nitrous oxide-oxygen analgesia group.

No statistically significant difference was found in oxygen saturation and heart rate amongst all four groups before the procedure, during the procedure, and after the procedure (Table/Fig 7).

Adverse reactions were most commonly seen in ketamine with 20% patients followed by N2O with 11.7% patients, midazolam with 8% patients, and no patient was seen having any adverse reactions in combination (M+K) group (p-value-0.034) (Table/Fig 8).


According to this study oral combination of midazolam-ketamine was most favourable than all other three groups. This result was per the study of Moreira TA et al., found that oral combination of midazolam and ketamine offered significantly better behaviour guidance than midazolam alone. Adding ketamine to midazolam may have enhanced the quality of sedation by adding analgesic effect without suppressing the upper airway reflex (15). Menon A et al., in their study used the Houpt scale to assess behaviour and concluded that oral ketamine is a better sedative agent than oral midazolam or even oral midazolam-oral ketamine combination in three to six year anxious paediatric dental patients but their results were statistically insignificant (16).

Lokken P et al., compared midazolam and combination midazolam with ketamine administered through rectal route. They found that children, who were sedated with combination showed lesser anxiety, were friendly and had lesser side-effects as compared to the one sedated with midazolam alone. Favorable effects must have been effects of ketamine which adds analgesia and counteracts the depressive effect of midazolam on vital functions. In addition, midazolam may have counteracted the psychic side effects of ketamine (17). The authors concluded that when midazolam was added to ketamine the side-effects were greatly reduced and the result and was also significant. Similarly in a study conducted by Sado-Filho J et al., where they compared intranasal and oral combination of midazolam and ketamine with oral midazolam and found that combination group showed better behavioural outcome as compare to midazolam alone (18). A study conducted by Pandey RK et al., comparing ketamine, midazolam, and their combination intranasally, found that Intranasal (IN) ketamine gave best results amongst (IN) midazolam (0.3 mg/kg) or the (IN) combination of ketamine and midazolam. The reason may be the large variance in the dose of ketamine (19). Ketamine was a better conscious sedative agent than midazolam in our study. Menon A et al. also found that an oral dose of ketamine (3 mg/kg) acted as better sedative agent than oral midazolam (0.5 mg/kg) (16). Similar to our results Rai K et al., found Intravenous (i.v) ketamine superior to i.v midazolam as a sedative agent in uncooperative three-six-year-old children undergoing dental procedures. Though midazolam showed the extended duration of action but could not induce desirable behaviour to complete the treatment (20). Moreover, Surendar MN et al., also found intranasal ketamine to be a better anxiolytic and sedative than intranasal midazolam, though vomiting was seen in one patient who was given ketamine (21). Foley J reported that nitrous oxide-oxygen sedation was less accepted by younger patients than to older age group children (22). The same results were found in our study where the patients in age group of less than four years showed significantly less acceptance for nasal mask and treatment could not be completed.

Nitrous oxide-oxygen was less effective than the K+M combination group in our study. While Ilasrinivasan JV and Shyamachalam PM compared N2O inhalation sedation oral midazolam–ketamine combination for the treatment of anxious children aged between three-ten years for dental treatment and found no statistically significant differences between the groups (23). In the present study, authors have assessed all sedative agents for the favourable and unfavourable outcome to find the best sedative agent with a favourable outcome.

In a study conducted by Wilson KE et al., the blood pressure, heart rate, and arterial oxygen saturation in both groups (oral midazolam and nitrous oxide-oxygen) were similar and within acceptable clinical limits. (24). Whereas in a study conducted by Vasakova J et al. after administration of midazolam, arterial blood pressure and blood oxygen saturation decreased and heart rate increased, with values staying within the limits of physiological range (25).

Darlong V et al. concluded in their study that the combination of oral ketamine and oral midazolam has the least side effects than either midazolam or ketamine alone (26). Moreover, Lokken P et al. compared midazolam (0.3 mg/kg) and midazolam with ketamine (1 mg/kg) as a rectal route. They found that side effects were more in the case of midazolam alone as compared to that of combination (17). A study conducted by Ilasrinivasan JV and Shyamachalam PM oral combination of the midazolam-ketamine group reported 6.7% hallucinations during the sedation procedure, and 20% overslept (23). In the present study, adverse reactions were most seen in ketamine followed by nitrous oxide-oxygen, midazolam, and no patient was seen having any adverse reaction in the combination (M+K) group.

In a study conducted by Galeotti A et al., the most frequent symptoms associated with nitrous oxide-oxygen oxygen sedation were nausea and vomiting (27). However, in this study no such adverse effects were noticed on the administration of nitrous oxide-oxygen except for watery eyes. A summary of all the studies has been presented in (Table/Fig 9) (15),(16),(17),(18),(19),(21),(23),(26).


Although, the use of moderate sedation shows significant changes in the behaviour outcome but there were few limitations of the study like eight (32%) children from the nitrous oxide-oxygen sedation group were excluded because they didn’t accept the nasal mask and the sedative agent couldn’t be initiated. Ketamine, midazolam, and nitrous oxide-oxygen show side effects like vomiting, hallucination, and watery eyes. More studies are required for the search for a predictable, safe and efficacious sedative agent.


Oral (midazolam+ketamine (M+K) regimen may be a significantly effective alternative to oral ketamine or midazolam alone or nitrous oxide-oxygen inhalation sedation in preschool children (three to five-year-old). This strategy may enable the paediatric dentist to tailor a sedation regimen friendly to both patients and parents, as K+M group showed no adverse effect. Ketamine acts as an analgesic to the combination K+M and decreases the depressive effect of midazolam on vital functions. Further the combination of local anesthesia with N2O sedation provides an effective analgesia where parents preferred their child not being put to sleep and has less recovery time than K/M regimen.


Authors express my sincere gratitude to my Head of the Department Dr. Anil Gupta for his invaluable guidance, encouragement, and healthy criticism. Authors are also incredibly thankful to my teachers and late respected Dr. Mohan Lal Khatri, Dr. Shalini Garg, and Dr. Ankit Srivastava for their valuable advice, constructive criticism, positive appreciation, and counsel of the investigations.


Viswanath D, Kumar M, Prabhuji ML. Dental anxiety, fear and phobia in children. Int J Dent Res Dev. 2014;4(1):01-04.
Schuurs AH, Hoogstraten J. Appraisal of dental anxiety and fear questionnaires: A review. Community Dentistry and Oral Epidemiology. 1993;21(6):329-39. [crossref] [PubMed]
Alaki S, Alotaibi A, Almabadi E, Alanquri E. Dental anxiety in middle school children and their caregivers: Prevalence and severity. J Dent Oral Hyg. 2012;4(1):06-11.
Mtalsi M, Hamza M, Elgasmi FE, Chlyah A, Hmamouchi B, Elarabi S. Conscious sedation by Midazolam in pediatric odontology: A randomised clinical trial. GSC Biological and Pharmaceutical Sciences. 2021;14(02):172-80. [crossref]
Sullivan DC, Wilson CF, Webb MD. A comparison of two oral ketamine-diazepam regimens for the sedation of anxious pediatric dental patients. Pediatr Dent. 2001;23(3):223-54.
Wilson KE, Girdler NM, Welbury RR. A comparison of oral midazolam and nitrous oxide sedation for dental extractions in children. Anaesthesia. 2006;61(12):1138-44. [crossref] [PubMed]
Al-Zahrani AM, Wyne AH, Sheta SA. Comparison of oral midazolam with combination of oral midazolam and nitrous oxide inhalation in relation to safety of dental sedation in young children. Odontostomatol Trop. 2011;34(135):33-41.
Roelofse JA, Louw LR, Roelofse PG. A double blind randomised comparison of oral trimeprazine-methadone and ketamine-midazolam for sedation of pediatric dental patients for oral surgical procedures. Anesth Prog. 1998;45(1):3.
Wasfy SF, Hassan RM, Hashim RM. Effectiveness and safety of Ketamine and Midazolam mixture for procedural sedation in children with mental disabilities: A randomised study of intranasal versus intramuscular route. Egypt J Anaesth. 2020;36(1):16-23. [crossref]
Bui T, Redden RJ, Murphy S. A comparison study between ketamine and ketamine-promethazine combination for oral sedation in pediatric dental patients. Anesth Prog. 2002;49(1):14.
Huang A, Tanbonliong T. Oral sedation post discharge adverse events in pediatric dental patients. Anesth Prog. 2015;62(3):91-99. [crossref] [PubMed]
Navit S, Johri N, Khan SA, Singh RK, Chadha D, Navit P, et al. Effectiveness and comparison of various audio distraction aids in management of anxious dental paediatric patients. Journal of Clinical and Diagnostic Research: JCDR. 2015;9(12):ZC05. [crossref] [PubMed]
Coté CJ, Wilson S. Guidelines for monitoring and management of pediatric patientsbefore, during, and after sedation for diagnostic and therapeutic procedures. Pediatr Dent. 2019;41(4):26E-52E.
Houpt MI, Weiss NJ, Koenigsberg SR, Desjardins PJ. Comparison of chloral hydrate with and without promethazine in the sedation of young children. Pediatr Dent. 1985;7(1):41-46.
Moreira TA, Costa PS, Costa LR, Jesus-França CM, Antunes DE, Gomes HS, et al. Combined oral midazolam-ketamine better than midazolam alone for sedation of young children: A randomised controlled trial. Int J Paediatr Dent. 2013;23(3):207-15. [crossref] [PubMed]
Menon A, Khatri ML, Gupta A, Srivastava A. Comparative evaluation of oral midazolam, oral ketamine and oral midazolam-ketamine combination as conscious sedative agents in uncooperative pediatric dental patients. IOSR-JDMS. 2016;11(15):31-36.
Lökken P, Bakstad OJ, Fonnelöp E, Skogedal N, Hellsten K, Bjerkelund CE, et al. Conscious sedation by rectal administration of midazolam or midazolam plus ketamine as alternatives to general anesthesia for dental treatment of uncooperative children. Eur J Oral Sci. 1994;102(5):274-80. [crossref] [PubMed]
Sado-Filho J, Viana KA, Corrêa-Faria P, Costa LR, Costa PS. Randomised clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation. PloS one. 2019;14(3):e0213074. [crossref] [PubMed]
Pandey RK, Bahetwar SK, Saksena AK, Chandra G. A comparative evaluation of drops versus atomized administration of intranasal ketamine for the procedural sedation of young uncooperative pediatric dental patients: A prospective crossover trial. J Clin Pediatr Dent. 2011;36(1):79-84. [crossref] [PubMed]
Rai K, Hegde A, Goel K. Sedation in uncooperative children undergoing dental procedures: A comparative evaluation of midazolam, propofol and ketamine. J Clin Pediatr Dent. 2007;32(1):01-04. [crossref] [PubMed]
Surendar MN, Pandey RK, Saksena AK, Kumar R, Chandra G. A comparative evaluation of intrnasal dexmedetomidine, midazolam and ketamine for their sedative and analgesic properties: A triple blind randomised study. J Clin Pediatr Dent. 2014;38(3):255-61. [crossref] [PubMed]
Foley J. A prospective study of the use of nitrous oxide inhalation sedation for dental treatment in anxious children. Eur J Paediatr Dent. 2005;6(3):121.
Ilasrinivasan JV, Shyamachalam PM. A Comparative evaluation of the sedative effects of nitrous oxide-oxygen inhalation and oral midazolam-ketamine combination in children. Int J Clin Pediatr Dent. 2018;11(5):399. [crossref] [PubMed]
Wilson KE, Welbury RR, Girdler NM. A randomised, controlled, crossover trial of oral midazolam and nitrous oxide for paediatric dental sedation. Anaesthesia. 2002;57(9):860-67. [crossref] [PubMed]
Vasakova J, Duskova J, Lunackova J, Drapalova K, Zuzankova L, Starka L, et al. Midazolam and its effect on vital signs and behaviour in children under conscious sedation in dentistry. Physiological Research. 2020;69:S305-14. [crossref] [PubMed]
Darlong V, Shende D, Subramanyam MS, Sunder R, Naik A. Oral ketamine or midazolam or low dose combination for premedication in children. Anaesth Intensive Care. 2004;32(2):246-49. [crossref] [PubMed]
Galeotti A, Garret Bernardin A, D’Antò V, Ferrazzano GF, Gentile T, Viarani V, et al. Inhalation conscious sedation with nitrous oxide and oxygen as alternative to general anesthesia in precooperative, fearful, and disabled pediatric dental patients: A large survey on 688 working sessions. Biomed Res Int. 2016;2016:7289310. [crossref] [PubMed]

DOI and Others


Date of Submission: Jan 15, 2021
Date of Peer Review: Feb 25, 2020
Date of Acceptance: May 19, 2021
Date of Publishing: Aug 01, 2021

• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

• Plagiarism X-checker: Jan 16, 2021
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• iThenticate Software: Jul 30, 2021 (18%)

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