The successful management of saliva and a good isolated operating area is a pre-requisite for majority of modern intraoral procedures. The challenge is amplified in paediatric practice due to limitations of communication and often comprehension from young patients. Herewith, the present study which was aimed to assess the use of sublingual atropine drops in children to decrease their salivary flow reversibly and assist the dental procedure requiring saliva control, shows promising results.
The use of ophthalmic eye drops with 1% w/v atropine sulphate, which is a commercially available over-the-counter drug, was done based on previously published works, most of which have demonstrated the effectiveness and success of this solution. Hyson et al (2002) reported the use of ophthalmic atropine drops in a brief report justifying the usage due to its ready availability, low cost, and no requirement of specialized skill while its administration. [4] A similar argument was made in the favour by Meningaud et el (2006) stating its reversible effect as an added benefit.[5] Other studies like the ones performed by Sockalingam et al, 2007, Rapoport, 2010, Mustafa et al 2013, Norderyd et al 2017 have also used the same rationale for administering atropine via ophthalmic drops. [6-9]
The route of administration of drug in the present study was sublingual. This was chosen to avoid unnecessary invasive procedures and to eliminate the first pass metabolism of drug unavoidable via the oral route. This guarantees that the drug enters the circulation faster than intramuscular or oral routes and potentiate higher absorption due to increased perfusion. [10] Also, this route has been the most used in relation with ophthalmic atropine drops in previous studies where their safety has been established, including in the paediatric population. [11, 12]
CORRELATION OF ATROPINE SULPHATE AND AGE AND WEIGHT OF THE PARTICIPANT
It has previously been demonstrated by Rashid and Bateman (1990) that age affects the salivary response to atropine. [13] The results of the present study show that the average unstimulated salivary flow rate of the participants of the study (n=60) aged 7-18 was 0.84ml/min at baseline. This is within range and comparable to previous works done on the subject by Forcella et al (2018) [14], where the mean USFR was found to be 0.76ml/min and other researchers all of whom have reported similar unstimulated flow rates in their studies in similar age groups. [15-18] It was shown in the present study that the atropine case group showed significant correlation to the ages of the participants at 60-minutes. (Table 1)
It has been recommended by the American Academy of Paediatrics, since 1950 that calculation of atropine dosage be made based on body weight. [19] The dose range of atropine in the present study ranged from 0.14 mg- 0.99 mg. In the current study it was seen that salivary flow rate was statistically correlated to the weight of the child in the control group. (Table 2) Body weight is a known factor affecting the salivary flow rate, especially in children. Increased weight of the child has been proven to reduce the salivary flow rate. These children show lower salivary flow rates as compared to children with normal range weight. [20] This could also be a reflection of developmental changes which encompass both height and weight and maturation of salivary glands affecting salivation. [21]
CORRELATION OF ATROPINE SULPHATE AND GENDER OF THE PARTICIPANT
The mean salivary flow rate estimated by both stimulated and unstimulated methods showed that males had a higher salivary flow rates as compared to females at the baseline. (Graph 1) This observation is in accordance with previous works by Anderson 1972, Heintze et al 1983 and Percival et al 1994 who concluded that at various age groups, females had lower mean salivary flow rates than males. [22-24] A possible explanation for the gender disparity has been proposed by associating salivary gland size with secretory capacity. [25] In the present study, at the subsequent readings at various time intervals, no difference was seen based on gender while computing the saliva quantitatively. Hence, atropine exerted similar antisialogogue effect on both girls and boys and showed no gender predilection on its pharmacokinetics.
DECREASE IN SALIVATION AFTER ATROPINE
It has long been proven that salivary secretion is extremely sensitive to inhibition by antimuscarinic agents. [26] In the current study it was recorded to have a stark drop in both USFR and SSFR over a period of 90 minutes after administration of atropine drops. (Graph 2) The unstimulated salivary flow rates in the children receiving atropine sulphate dropped by 80.3% in 90 minutes whereas stimulated salivary flow rate decreased by 79.4%. This seemed to echo the findings by Volz-Zang et al (1995) who reported the decline of 84.3% salivation after oral atropine administration in their subjects. [27] This also substantiates the already established fact of the antisialogogue activity of the drug as demonstrated by Bowman and Rand (1980) [28] and Iliopoulou et al (1981) [29] at the dosage and route chosen [7,9] within a span of 90 minutes.
COMPARING THE EFFECTIVENESS OF ATROPINE DROPS ON SALIVATION BETWEEN THE TWO STUDY GROUPS
Quantitative Analysis
In our study, the USFR saw significant correlation between the two study groups at 90 minutes interval. This difference was highly statistically significant, which goes on to show that atropine produced maximum quantitative effect on salivation at the interval of 90 minutes. (Graph 3) When analysing the SSFR in the study group, it was seen that the cases and control groups showed statistically significant correlation across all three time intervals. This finding of the steep decline of the SSFR in all the children who received atropine signifies the anticholinergic action of atropine that inhibit the action of M3 receptors causing the salivary gland hypofunction. [30] When given the same dose as the present study, administered sublingually using insulin injectors, authors achieved similar results in children of 3-78 months of age. [31]
Time Interval
The findings of the current study go on to show that the salivary flow rates progressively regress over the period of 90 minutes when final readings were taken. The USFR declined from 0.95 ml/min at start to a mere 0.19 ml/min at the end of 90 minutes. This shows the although the action of atropine starts to take effect before one hour, the peak action is evidenced only after 90 minutes. A similar decline could be viewed for SSFR where the reduction in salivary flow was drastic at 90minutes at 0.25 ml/min from 1.23 ml/min at the start. (Graph 3) The present findings seem to echo that of Mirakhur et al (1979), where oral atropine produced significant oral mucosal dryness at 90 minutes. [32] This could be explained as the peak serum concentration of AS when given the same oral dose as the present study, has been documented at 2 hours (6.7 nmol/l) that decreased the salivation until this time in children with a mean age of 5.1 years. [33] Kazen and Dille (1963) concluded a similar 90-minute period for maximum effect of AS when given orally, which then persisted for another two and a half hours.[34]
As per the present study design, the time of observation was found to be inadequate to chart the reversal of the salivary flow in the participants. The only conclusion that could be drawn from the present study was that the antimuscarinic effect of atropine persists even after 90 minutes of the drug. This is a substantiated claim by Brion et al (1988), according to whom saliva volume did not revert up until 7 hrs of 1mg atropine tablet. [35]
EFFECT OF ATROPINE SULPHATE ON VITALS
The administration of atropine sulphate in the dosages of 1.5 mg orally has been known to cause change in diastolic blood pressure [36] something that was demonstrated by the present study where there was an increase in diastolic Blood Pressure (BP) in children who received atropine drops within 60 minutes of intake. This increase in the diastolic BP was found to be transient and had stabilized to its normal range by the final reading at 90 minutes. (Graph 4)
A decrease in heart rate was observed in all the children receiving atropine drug sublingually at 60 minutes interval in the current study. The heart rate was found to revert to the normal range within the span of the study. (Graph 5) This transient decrease of heart rate was expected as is known to occur associated with low doses of atropine and thought to be caused due to central vagal effect either on the nucleus or a direct effect on the heart. [37-39] In this context, the most accepted explanation has been that it’s the peripheral effects that contribute more as compared to CNS effects when causing bradycardia in children. [36] Recent studies also report a decrease in standing pulse rate echoing the results of the present study. [40]