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

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.

Study Overview

• Status: Completed
• Conditions: Analgesia; Sedation Complication; Bronchospasm; Ketamine Toxicity

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 57

Contacts and Locations

Study Locations

• Italy
  • PD
    • Padova, PD, Italy, 35127
      • Azienda Ospedale Universita Padova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study population is composed by paediatric patients admitted in PICU treated with ketamine (lasted more than 12 hours) during mechanical ventilation in the studied period.

Description

Inclusion Criteria:

• pediatric intensive care unit admission
• mechanical ventilation
• ketamine infusion > 12 hours

Exclusion Criteria:

• parents refusal to participate

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ketamine group; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
presence of hypotension	change of inotropic therapy after ketamine infusion	12 hours

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera di Padova
• Investigators: Principal Investigator: angela amigoni, MD, Azienda Ospedaliera di Padova; Study Director: andrea pettenazzo, MD, Azienda Ospedaliera di Padova

Publications and helpful links

General Publications

• Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018 Jul;70(3):621-660. doi: 10.1124/pr.117.015198. Erratum In: Pharmacol Rev. 2018 Oct;70(4):879.
• Heiberger AL, Ngorsuraches S, Olgun G, Luze L, Leimbach C, Madison H, Lakhani SA. Safety and Utility of Continuous Ketamine Infusion for Sedation in Mechanically Ventilated Pediatric Patients. J Pediatr Pharmacol Ther. 2018 Nov-Dec;23(6):447-454. doi: 10.5863/1551-6776-23.6.447.
• Miller AC, Jamin CT, Elamin EM. Continuous intravenous infusion of ketamine for maintenance sedation. Minerva Anestesiol. 2011 Aug;77(8):812-20.
• Golding CL, Miller JL, Gessouroun MR, Johnson PN. Ketamine Continuous Infusions in Critically Ill Infants and Children. Ann Pharmacother. 2016 Mar;50(3):234-41. doi: 10.1177/1060028015626932. Epub 2016 Jan 18.
• Neunhoeffer F, Hanser A, Esslinger M, Icheva V, Kumpf M, Gerbig I, Hofbeck M, Michel J. Ketamine Infusion as a Counter Measure for Opioid Tolerance in Mechanically Ventilated Children: A Pilot Study. Paediatr Drugs. 2017 Jun;19(3):259-265. doi: 10.1007/s40272-017-0218-4.
• Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ann Emerg Med. 2005 Jul;46(1):43-50. doi: 10.1016/j.annemergmed.2005.02.024.
• Petrillo TM, Fortenberry JD, Linzer JF, Simon HK. Emergency department use of ketamine in pediatric status asthmaticus. J Asthma. 2001 Dec;38(8):657-64. doi: 10.1081/jas-100107543.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 12, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: ketamine; sedation; pediatric intensive care unit
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchial Spasm
• Other Study ID Numbers: AOP1795; CESC (Local Ethic Committee for clinical trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No