Ketamine Efficacy for Acute Severe Bronchospasm in ICU: MACANUDO Trial (MACANUDO)

Ketamine Efficacy for Acute Severe Bronchospasm in Mechanically Ventilated-critically Ill Patients: a Randomized Controlled Trial

Despite few scientific evidence that could support the use of ketamine in adult patients undergoing acute bronchospasm requiring mechanical ventilation (MV), ketamine is largely employed in this setting. The aim of this study is therefore assess more definitively the real benefit of using ketamine in patients with severe bronchospasm, requiring ICU stay and need for MV in order to establish or refute the use of this drug as "standard therapy" in these cases.

Study Overview

• Status: Unknown
• Conditions: Critical Illness; Asthma; Bronchospasm
• Intervention / Treatment: Drug: Fentanyl; Drug: Ketamine

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil
    • Recruiting
    • Hospital Nossa Senhora da Conceição
    • Contact: Wagner Nedel, MD, MSc; Email: wagnernedel@uol.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• patients with acute exacerbation of COPD or status asthmaticus, undergoing controlled mechanical ventilation
• acute bronchospasm, defined as airway resistance value (Rsr max) greater than 12, use of inhaled therapy with bronchodilators and systemic corticosteroids
• patients requiring the use of continuous intravenous sedation for optimization of ventilation

Exclusion Criteria:

• contraindication or history of previous adverse events with the use of the studied drugs
• other diagnostic potential Rsr increase of not causing bronchospasm (bronchial obstruction, acute respiratory distress syndrome adult, pulmonary fibrosis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; Intravenous ketamine infusion: bolus 2mg per kg and continuous infusion (2mg/kg/h)	Drug: Ketamine; Active treatment
Active Comparator: Fentanyl; Fentanyl: bolus infusion 1μg per kg and continuous infusion (1μg/kg/h)	Drug: Fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bronchospasm improvement	Maximal airway resistance reduction in hour 3-post beginning of drug infusion	3 hours post beginning of drug infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bronchospasm improvement	Maximal airway resistance reduction in 24th hour post beginning of drug infusion	24 hours post beginning of drug infusion
Time to weaning	Time (in days) to first spontaneous breathing trial post randomization up to 28 days	Time (in days) to first spontaneous breathing trial post randomization up to 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamic complacence improvement		3 hours and 24 hours post beginning of drug infusion
Air trapping improvement	intrinsic PEEP reduction in 3 and 24h post beginning of drug infusion	3 hours and 24 hours post beginning of drug infusion
Heart rate	Heart rate in 3 hours and 24h post beginning of drug infusion	3 hours and 24 hours post beginning of drug infusion
Blood pressure	Blood pressure variation in 3 hours and 24hours post beginning of drug infusion	3 hours and 24 hours post beginning of drug infusion

Collaborators and Investigators

• Sponsor: Hospital Nossa Senhora da Conceicao

Publications and helpful links

General Publications

• Miller AC, Jamin CT, Elamin EM. Continuous intravenous infusion of ketamine for maintenance sedation. Minerva Anestesiol. 2011 Aug;77(8):812-20.
• 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.
• Barbas CS, Isola AM, Farias AM, Cavalcanti AB, Gama AM, Duarte AC, Vianna A, Serpa Neto A, Bravim Bde A, Pinheiro Bdo V, Mazza BF, Carvalho CR, Toufen Junior C, David CM, Taniguchi C, Mazza DD, Dragosavac D, Toledo DO, Costa EL, Caser EB, Silva E, Amorim FF, Saddy F, Galas FR, Silva GS, Matos GF, Emmerich JC, Valiatti JL, Teles JM, Victorino JA, Ferreira JC, Prodomo LP, Hajjar LA, Martins LC, Malbouisson LM, Vargas MA, Reis MA, Amato MB, Holanda MA, Park M, Jacomelli M, Tavares M, Damasceno MC, Assuncao MS, Damasceno MP, Youssef NC, Teixeira PJ, Caruso P, Duarte PA, Messeder O, Eid RC, Rodrigues RG, Jesus RF, Kairalla RA, Justino S, Nemer SN, Romero SB, Amado VM. Brazilian recommendations of mechanical ventilation 2013. Part I. Rev Bras Ter Intensiva. 2014 Apr-Jun;26(2):89-121. doi: 10.5935/0103-507x.20140017.
• Rowe BH, Sevcik W, Villa-Roel C. Management of severe acute asthma in the emergency department. Curr Opin Crit Care. 2011 Aug;17(4):335-41. doi: 10.1097/MCC.0b013e328348bf09.
• Heshmati F, Zeinali MB, Noroozinia H, Abbacivash R, Mahoori A. Use of ketamine in severe status asthmaticus in intensive care unit. Iran J Allergy Asthma Immunol. 2003 Dec;2(4):175-80.
• Howton JC, Rose J, Duffy S, Zoltanski T, Levitt MA. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Ann Emerg Med. 1996 Feb;27(2):170-5. doi: 10.1016/s0196-0644(96)70319-0.
• Goyal S, Agrawal A. Ketamine in status asthmaticus: A review. Indian J Crit Care Med. 2013 May;17(3):154-61. doi: 10.4103/0972-5229.117048.
• Abu-Hijleh M, El-Sameed Y, Eldridge K, Vadia E, Chiu H, Dreyfuss Z, Al Rabadi LS. Linear probe endobronchial ultrasound bronchoscopy with guided transbronchial needle aspiration (EBUS-TBNA) in the evaluation of mediastinal and hilar pathology: introducing the procedure to a teaching institution. Lung. 2013 Feb;191(1):109-15. doi: 10.1007/s00408-012-9439-z. Epub 2012 Dec 4.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimate): December 22, 2016

Study Record Updates

• Last Update Posted (Estimate): December 22, 2016
• Last Update Submitted That Met QC Criteria: December 19, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Bronchial Diseases; Critical Illness; Bronchial Spasm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Ketamine; Fentanyl
• Other Study ID Numbers: 42324015.0.0000.5530