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Dr. Mamta Gupta,
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Aug 2018

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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.
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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 : 2012 | Month : February | Volume : 6 | Issue : 1 | Page : 65 - 68

Midazolam Pre-medication in Paediatrics: Comparison of the Intranasal and Sublingual Routes by Using an Atomizer Spray

Narendra kumar, Rohit Sharma, Mamta Sharma, Indu Verma, Meenaxi Sharma

1. Post graduate student, Department of Anaesthesiology, S.M.S Medical College and Attached Hospitals, Jaipur, Rajasthan (INDIA). 2. Assistant professor, NIMS dental hospital, Jaipur. 3. Associate Professor, Department of Anaesthesiology, S.M.S Medical College and Attached Hospitals, Jaipur, Rajasthan (INDIA). 4. Associate Professor, Department of Anaesthesiology, S.M.S Medical College and Attached Hospitals, Jaipur, Rajasthan (INDIA). 5. Professor, Department of Anaesthesiology, S.M.S Medical College and Attached Hospitals, Jaipur, Rajasthan (INDIA).

Correspondence Address :
Dr. Narendra kumar
3/57, sector-3, Jawahar nagar, Jaipur (Rajasthsan)
Phone: 09982348741


Most of the children suffer from severe anxiety and apprehension when they are separated from their parents or family members for the induction of anaesthesia.
Materials and Methods:
In a prospective randomized double blind study, the intra-nasal and sub-lingual administration of midazolam in paediatric patients who were undergoing root canal procedures which required general anaesthesia was evaluated in 60 children who were aged between 2-6 years, with ASA physical status I and II by using a new midazolam atomiser spray. The patients were divided into two groups of 30 patients each and they received midazolam 0.3mgkg-1 either intranasally or sub-lingually in a randomized manner. The heart rate, oxygen saturation (spo2), respiratory rate and the degree of sedation before and at 5 min, 10 min and 15 min (separation score) after the drug administration, during the mask application (mask acceptance score), before induction (induction score) and during the recovery at 10 min, 20min and 30mins (recovery score) were recorded and compared.
In our study, 60% of the paediatric patients cried during the administration of midazolam by the intra-nasal route, while only 16% of the paediatric patients cried during its administration by the sub-lingual route. A bitter taste was observed in 45% (14/30) of the patients who received midazolam by the sublingual route. Although there was a slight increase in the heart rate in the intra-nasal group, no statistically significant variation in the heart rate, the respiratory rate and the oxygen saturation was found from the baseline in both the groups (P>0.05). A sedation score of >3(approx) was achieved in both the groups within 10 minutes of the drug administration. The response to the child parent separation, the mask application score , the induction score and the recovery score did not differ significantly between the two groups ( P >0.05).
Both the intra-nasal and sub-lingual administration of midazolam as a Pre-medication is safe and equally effective in paediatric patients.


Pre-medication, Paediatrics, Intra-nasal, Sub-lingual, Midazolam Atomiser spray

Most of the children suffer from severe anxiety and apprehension when they are separated from their parents or family members for the induction of anaesthesia (1). The unfamiliar faces and the environment inside the operating room compound a sense of insecurity in the children (2). Thus, pre-operative anxiety can largely affect the smoothness of the induction, the emergence from anaesthesia and also the psychological and emotional state of the children in the remote future (3). Maladaptive behavioural response such as general anxiety, nighttime crying, enuresis and separation anxiety occur in up to 44% of the children, two weeks after the operation. Twenty percent of these children will continue to demonstrate a negative behaviour even 6 months after the surgery (3). Although non-pharmacological means in the form of friendly visits by the anaesthesiologist to establish a rapport with the children and briefing about the procedure whenever feasible help to minimize the children’s anxiety, pharmacological agents are often helpful to provide sedation and to promote a smooth induction. Even parental presence inside the operation theatre may not be fully effective. Sedative Pre-medication may be more effective in this regards (4). Sedative Pre-medications can be administered orally, intramuscularly, intravenously, rectally, sub-lingually or nasally. Although Original Article Anaesthesia Section most of these routes are effective and reliable, each has drawbacks. Oral or sub-lingual Pre-medication do not hurt, but they may have a slow onset or may be spit out and drug taste is the main determinant for the success of their administration. Intra-muscular medications may hurt and may result in a sterile abscess. Intravenous medications may be painful during injection or at the start of the infusion. Rectal medications may sometimes make the children feel uncomfortable and they may cause defecation, and occasionally burns. Nasal medications can be irritating, although their absorption is rapid. The ideal agent should have a rapid onset, a predictable duration and a rapid recovery. There are many drugs which are used for premedicating children. Ketamine, clonidine, fentanyl, buprenprphine and midazolam are the ones which are most commonly used in the clinical practice. We used a new midazolam atomiser spray. In this spray, the drug is delivered in puffs which contain very minute particles which spread over a large surface area. The present study was designed to compare the safety, the acceptability and the degree of sedation which was produced by intra-nasal and sub-lingual midazolam as a pre-anaesthetic medication in paediatric patients who were undergoing elective dental procedures under general anaesthesia.

Material and Methods

After obtaining written and informed consent from the parents, sixty ASA I and II children who were aged between 4-10 years and were scheduled for elective surgical procedures under general anaesthesia were enrolled in the study. Children with respiratory and cardiac diseases or those who had upper respiratory tract infections were excluded from the study. All the patients were brought to the reception area of the operation theatre complex along with their parents and were randomly allocated to one of the two groups of 30 patients each. Group I (the sub-lingual group) received midazolam 0.3mgkg-1. The children were asked to touch their upper teeth with the tip of their tongues and then, the midazolam atomizer was sprayed beneath the tongue, while not permitting the children to swallow the drug for 20 seconds. In group II (the intra-nasal group), the midazolam 0.3mgkg-1 atomizer was sprayed in both the nostrils with the children in a semi-recumbent position or in a parent’s lap. To avoid interobserver variations, the same anaesthesiologist was involved in all the assessments, who was also kept blind to the route of administration which was used by the attending nurse. The patient’s responses to the drug administration were noted. The heart rate, respiratory rate and oxygen saturation rate were recorded before and at 5 and 10 minutes after the administration of the drug. The degree of sedation also was assessed at 0.5 and 10 minutes after the drug administration, by using a 5 point sedation scale, as shown in (Table/Fig 1). At 15 minutes, the children were separated from their parents and were taken to the operating room. The responses to the child parent separation were assessed by using a separation score and they were graded according to a 4 point separation score as was used by Davis et al (Table/Fig 1) (5).Scores 1 and 2 were considered as satisfactory and scores 3 and 4 as unsatisfactory. The intravenous line was accessed. The patients were premedicated with glycopyrrolae 0.008mg/kg and tramadol 1mg/kg intravenously. Just before induction, the sedation was assessed by using an induction score. The patient was induced with oxygen (O2), nitrous oxide (N2O) and halothane by using a facemask. The response to the mask was assessed by using a mask acceptance scale (Table/Fig 2).Thus, if a patient was drowsy but refused mask induction, then the patient was recorded to have score 1 and not 4. Scores 1 and 2 were considered as unatisfactory and score 3 and above as satisfactory. The induction score was assessed in the children just before the induction of anaesthesia. Nasotracheal intubation was facilitated by using suxamethonium 2mg/kg i.v. Anaesthesia was maintained by using oxygen, nitrous oxide, halothane 0.5 to 1% and atracurium. The ventilation was controlled by using Jackson Ree’s modification of Ayre’s T-piece. The patients were reversed by using neostigmine 0.08mg/kg and glycopyrrolate 0.016mg /kg. Extubation was done after the children were fully awake. The post-operative sedation was assessed in the post anaesthesia recovery unit (PACU) at ten min intervals for thirty min by using a ten point recovery scale which assessed the patient’s colour, airway, respiration, the level of consciousness and movement (each on a scale of 0-2) to give a maximum cumulative total of 10. Side effects were noted in both the groups, if any. The data was compiled and analyzed statistically by using the Student’s ‘t’ test and a ‘p’-value of <0.05 was considered as significant. All the scores in our study were analyzed by using the Student’s t test and the sex ratio was analyzed by using the Chi-Square test. The software which was used for the statistical analysis was “Trimer of Boistatistics”.


The groups were comparable with respect to age, gender and weight (Table/Fig 3) There was no statistically significant difference in the heart rate, the respiratory rate and the oxygen saturation between the two groups before the administration of the drug (p>0.05). 18(60%) children in the intra-nasal group cried in response to the drug administration, as compared to only 5(16.6%) children in the sub-lingual group. This difference between the two groups was statistically highly significant [p<0.001]. Adequate oxygen saturation (>95%) was maintained in all the children in both the groups throughout the study. Changes in the heart rate, respiratory rate and the sedation score after the administration of the drug in the two groups are shown in (Table/Fig 4). A slight increase in the heart rate was observed in the intranasal group after the drug administration as compared to that in the sub-lingual group, but there was no statistically significant variation in the heart rate and the respiratory rate in both the groups when they were compared to the baseline values [p>0.05]. After 10 minutes of drug administration, a sedation score of more than 3 was achieved in 80% of the children in the sub-lingual group, as compared to 82% children in the intra-nasal group, which was statistically significant (p<0.05). Similarly, a satisfactory child parent separation score was observed in 85% and 89% children in the intra-nasal and the sub-lingual groups respectively, whereas the response before induction (the induction score) was also satisfactory in more than 90% of the children in both the groups. The response to the mask application, as was assessed by using the mask acceptance score, was satisfactory in both the groups. The recovery room score was also comparable in both the groups. No statistically significant difference was noted in both the groups. (Table/Fig 4).


Pre-anaesthetic medication in children is an important adjunct to help in alleviating the stress and the fear of surgery, as well as to case the child parent separation and to promote a smooth induction of anaesthesia. Midazolam, as a potent imidazo-benzodiazepine, has got all the required properties, namely sedative, hypnotic and anxiolytic activities. Midazolam is used for pre-operative sedation by the intra-muscular (IM) (6),(7),(8), rectal (9),(10), oral (11) and the sublingual routes (12),(13), but each route has its own advantages and disadvantages. The use of intra-nasal or sub-lingual midazolam as a Pre-medication has come into practice right from the early nineties(14),(15) Intranasal midazolam, in this regards, has got some advantage. Owing to its high mucosal vascularity, the intra-nasal route offers a rapid and virtually complete absorption within one-two hours into the systemic circulation (16). As midazolam has high hepatic clearance, the avoidance of the hepatic first pass metabolism offers greater systemic bioavailability (14),(15),(16). It has a faster onset than the oral or the rectal route. The recovery from anaesthesia is also not affected even after minor surgeries. Although sedation was achieved with 0.2mg/kg midazolam intranasally, the sedation by the sub-lingual route of the same dose was inadequate (there were chances of partly swallowing it). Thus, a dose of 0.3 mg/kg was selected for both the routes to make it comparable. The heart rate and the respiratory rate in both the groups remained stable and they did not show any significant variation from the baseline values in our study. These findings indicated the safety of midazolam which was given by either route and in the doses which were studied. Minor respiratory depression was observed by Fukuta et al (17) with 0.2mgkg-1 of intra-nasal midazolam. Similarly, Malinovsky et al (18) reported a case of respiratory depression in a 30 month old child which was given intra-nasal midazolam, attributing that to the ethmoidal passage of the drug which resulted in high CSF levels. In many studies, it was noted that the oxygen saturation remained above 95% in a majority of the cases which were pre-medicated with transmucosal midazolam. This was confirmed in our study also, where the oxygen saturation was maintained above 95% in all the children, irrespective of whether they were pre-medicated by the nasal or the sub-lingual route. However, the desaturation to less than 93% with 0.2mgkg-1 of intra-nasal midazolam, which was noted by Karl et al (19) in a small percentage of children, suggested close respiratory monitoring and the availability of resuscitation equipment when the intra-nasal route was used. Adequate sedation (score >3) after 10 minutes of drug administration, which was noted in a majority of the children in the sub-lingual group as compared to the intra-nasal group in our study, was in concordance with the findings of many studies, including the study of Karl et al (19). Karl et al noted that at the point of maximum anxiolysis, that is, at 10 minutes after the administration, midazolam, by the sub-lingual route, had produced a significant decrease in the apparent anxiety in a majority of the patients. Although the total buccal and sub-lingual area is small and it has a pH of 6.2-7.4, it has a potential for the rapid absorption of drugs, since these areas are rich in blood and lymphatic vessels. The drug directly passes into the systemic circulation and thus the first pass metabolism of the drug can be avoided. The lower incidence of adequate sedation through the intra-nasal route, as was observed in our study, also could be attributed to the shorter stay time of the drug in the nasal mucosal surface as was suggested by DeBoer et al (20) Since a majority of the children in our study were calm and relaxed (score>3), the child parent separation and the induction scores were satisfactory in both the groups. In our study, the separation score between the two groups was not statistically significant and there was no major side effect in any group. Nasal irritation and crying was found in 56% of the patients in group I immediately after the drug administration. A bitter taste was reported in 50% of the patients in group II. The increased incidence of crying with respect to the nasal route has been attributed by these authors (12) to the low pH of midazolam (pH 3.3), which causes burning or irritation of the nasal mucosa on administration.


Thus, we conclude that both the intra-nasal and the sub-lingual routes of administration of midazolam are equally effective and that they provide adequate sedation for the easy separation of children from their parents and the co-operation from children during the induction of anaesthesia. So, we recommend the routine use of both the intra-nasal and sub-lingual midazolam atomizers as a preanaesthetic medication in paediatric patients who undergo dental procedures under general anaesthesia. However, its use in all the paediatric surgeries needs further evaluation.


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Kain ZN. Perioperative psychological trauma in children. In the Chapter, Complication in Anesthesia, 1st edn. Philadelphia: W. B Saunders, 1990; 682-85.
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Date of Submission: Jun 12, 2011
Date of Peer Review: Oct 14, 2011
Date of Acceptance: Jan 02, 2012
Date of Publishing: Feb 15, 2012

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