Oral Lorazepam is not Superior to Placebo for Lowering Stress in Children Before Digestive Endoscopy: A Double-Blind, Randomized, Controlled Trial

Abstract

Background

Digestive endoscopies must be performed within a safe and comfortable environment. We have previously shown that the quality of intravenous sedation is influenced by preoperative stress.

Aim

Our primary objective was to compare the effects of oral lorazepam and placebo on the salivary cortisol response of children undergoing a digestive endoscopy. Secondary objectives were the assessment of procedural pain and comfort as well as the occurrence of adverse events.

Methods

Participants were randomized and received either lorazepam, placebo, or no premedication. Saliva was collected upon arrival at the hospital and 1 h following randomization. The sedation protocol included midazolam and fentanyl ± ketamine. Procedural pain was evaluated with the Nurse Assessed Patient Comfort Score (NAPCOMS). Patients completed a postoperative questionnaire. The primary outcome was defined as the proportion of children having a cortisol decrease ≥ 15 nmol/L.

Results

101 participants (54 females) were included. The rate of children having a cortisol decrease ≥ 15 nmol/L was 27.3%, 35.3%, and 19.4% for lorazepam, placebo, and no premedication, respectively (p = 0.356). The median (IQR) NAPCOMS pain score was 3.0 (0–6) for lorazepam, 4.4 (0–6) for placebo, and 3.4 (3–4) for no premedication (p = 0.428). With lorazepam, 75.9% of children reported experiencing a comfortable procedure, compared with 41.9% taking placebo and 34.5% with no premedication (p = 0.013). Transient tachycardia was the most frequent intraoperative adverse event, particularly with lorazepam (62.5%, p = 0.029).

Conclusions

Oral lorazepam had no effect on patients’ preoperative stress, as measured by salivary cortisol, but was associated with a higher rate of comfortable procedures.

Clinical Trial Registration

Clinicaltrials.gov, Identifier NCT03180632.

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Fig. 1

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Acknowledgements

We wish to express our thanks to all the participants of the trial and the endoscopists of the pediatric gastroenterology division at CHU Sainte-Justine (Colette Deslandres, Martha Dirks, Éric Drouin, Christophe Faure, Véronique Groleau, Kelly Grzywacz, Ugur Halac, Valérie Marchand, and Massimiliano Paganelli). We would also like to thank the research coordinator Anik Cloutier from Anne-Monique Nuyt Lab who provided assistance for the storage and the analysis of salivary cortisol samples.

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Correspondence to Prévost Jantchou.

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Funding

This work was funded by the Fonds de la Recherche du Québec-Santé (FRQS, 30646), the Canadian Association of Gastroenterology (CAG), and the Canadian Medical Protective Association (CMPA).

Conflict of interest

Fella Chennou, Alexanne Bonneau-Fortin, Olivia Portolese, Lina Belmesk, Melissa Jean-Pierre, Dre. Geneviève Côté, Dre. Martha H. Dirks and Dr. Prévost Jantchou have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Research Ethics Board of CHU Sainte-Justine; 2017-1559) and with the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study as well as their parents or legal guardians.

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Chennou, F., Bonneau-Fortin, A., Portolese, O. et al. Oral Lorazepam is not Superior to Placebo for Lowering Stress in Children Before Digestive Endoscopy: A Double-Blind, Randomized, Controlled Trial. Pediatr Drugs 21, 379–387 (2019). https://doi.org/10.1007/s40272-019-00351-9

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