Efficacy and Safety of Continuous Infusion of Ketamine in Pediatric Intensive Care Unit (KISS Study)

Study Overview
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Brief Summary
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This study, prospectively evaluate the efficacy and safety of ketamine administered in continuous infusion lasted more than 12 hours in children admitted to Pediatric Intensive Care Unit of Padova. This drug may be used as adopted as adopted as adjuvant to analgesia and sedation or as adjuvant to bronchospasm therapy. The investigators evaluated efficacy considering the sparing of other analgesics and sedatives and the level of sedation after ketamine infusion for the first use and the sparing of other bronchospasm drugs sedative dosage for the second use. To evaluate safety the investigators considered the presence of adverse effects and onset of withdrawal and delirium syndrome. The study will included al least 55 pediatric patients < 18 years and mechanically ventilated.

Detailed Description
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Ketamine is an N-Methyl-d-aspartate-receptor-antagonist commonly used over the last decades as an anesthetic and analgesic agent for procedural sedation. The use of ketamine as a prolonged infusion was first described in 1990 and a prolonged infusion of ketamine has been described as a successful strategy for analgesia and sedation in patients with hemodynamic instability, in patients who were mechanically ventilated and poorly responsive to conventional drugs. An other indication for ketamine infusion is the presence of bronchospasm, due to its action in promoting bronchodilatation. However, existing studies on ketamine for prolonged sedation are mainly retrospective and include small sample size, suggesting that this topic needs to be further investigated. The aim of this observational single center study is to describe the use of ketamine used as adjuvant to conventional analgesic and sedative strategy (opioid and benzodiazepine in continuous infusion) as prolonged infusion (i.e. ≥ 12 hr) in pediatric patients. The investigators will evaluate ketamine indications, dosages, infusion duration, adoption of boluses, modality of weaning. Concomitant analgesic and sedative management and monitoring of level of sedation (using a validated scale) are considered measures of efficacy. Sparing of other bronchospasm drugs sedative dosage are considered measures of efficacy if ketamine is used in patients with obstructive respiratory diseases. Presence of adverse effects (including withdrawal syndrome symptoms and delirium) during infusione or 48 hours after weaning are considered measures of safety. Data were collected using a standardized data sheet. The study lasted 18 months to reach a numerosity of 55 patients. All the requested institutional approvals were collected before starting the data collection.

Official Title
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Efficacy and Safety of Continuous Infusion of Ketamine in Pediatric Intensive Care Unit (KISS Study)

Conditions
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Analgesia, Ketamine Toxicity, Bronchospasm, Sedation Complication

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pediatric intensive care unit admission mechanical ventilation ketamine infusion > 12 hours Exclusion Criteria: parents refusal to participate

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ketamine group<br>ketamine intravenous infusion in pediatric patients refractory to conventional analgesic-sedative strategy lasted more than 12 hours (dose range 10-50 mcg/Kg/min) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| level of sedation measured with Comfort Behavior Scale (CBS) | CBS score decreased > 2 points after ketamine administration | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence adverse effects,delirium and withdrawal syndrome, assessed by physician (also using Cornell Assessment scale of Pediatric Delirium and Withdrawal Assessment tool 1) | incidence of adverse effects and number of patients withf delirium (Cornell Assessment scale of Pediatric Delirium) and withdrawal syndrome (Withdrawal Assessment tool 1) | evaluation during all the duration of ketamine infusion till to 48 hours after the end of it | 
| bronchospasm severity | change of bronchodilator after ketamine infusion | 12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric intensive care unit, ketamine, sedation