Introduction: Laceration is common in children presenting to the emergency department (ED). They are often uncooperative related to pain and distressed during repair. Currently, there are wide variations regarding sedation and analgesia practices when sutures are required. There is a growing interest in the intranasal (IN) route for procedural sedation and pain control because of its effectiveness potential and ease of administration. Few studies have evaluated IN ketamine for procedural sedation in children with reported doses ranging from 3 to 9 mg/kg. The objective is to evaluate the optimal IN ketamine dose for effective and safe procedural sedation for laceration repair in children aged 1 to 12 years. Methods: A dose escalation clinical trial with an initial dose of 3 mg/kg of IN ketamine up to a maximum dose of 9 mg/kg in children 1 to 12 years old, using a 3+3 trial design. For each tested dose, 3 patients are enrolled. Escalation to the next dose is permitted if sedation is unsuccessful in at least one patient without serious adverse event (SAE). Regression to prior dose is warranted in the occurrence of two or more SEAs. This process is repeated until effective sedation for 6 patients at two consecutive doses is achieved with a maximum of 1 SAE or if regression occurs. The primary outcome is the optimal dose for successful procedural sedation as per the PERC/PECARN consensus criteria. Secondary outcome, namely, pain and anxiety levels, parent, patient and provider satisfaction, recovery time, length of stay in the ED, side effects and adverse event are recorded. Results: Nine patients have been recruited from March to December 2017 with median age of 2.9 years-old and with laceration length of 2 to 5 cm and with facial involvement in 55% of cases, respectively. Sedation was successful in 1/3, 1/3 and 3/3 of patients at doses of 3, 4, 5 mg/kg respectively, without any SAE. Median time from ketamine administration to return to baseline status and discharge were 35 and 98 min, respectively. We expect to complete patient recruitment in March 2018. Conclusion: The results from our trial is a groundwork for future dose-finding study. Pending study completion, a multicentric dose validation trial, is set up to further validate the optimal dose from dosINK1 trial. IN ketamine has the potential to improve the field of procedural sedation for children by introducing an effective IN agent with respiratory stability but without the need for an IV line insertion not otherwise needed.
Incorporating adverse event relatedness into dose-finding clinical trial designs