Neuromuscular Blocking Agents in the Elderly

• Sponsor: Rigshospitalet, Denmark (Other)
• Overall Status: Completed
• CT.gov ID: NCT03857750
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Actual Duration (Months): 6.4
• Patients Per Site Per Month: 5

Study Details

Study Description

Brief Summary

The number of elderly patients (>80 years) is increasing and a large proportion of these patients will require surgery and anaestheasia within the next decades.

During anaesthesia NMBAs are used to facilitate tracheal intubation, from former studies it is reported that elderly patients are more sensitive towards muscle relaxants.

It is unknown if there are differences in onset times of NMBAs between younger patients and elderly.

The aim of this study is to determine the onset time, duration of action and effect on intubating conditions for rocuronium 0.6 mg/kg in patients aged 18-40 years and in patiens

80 years. The hypothesis of this study is that rocuronium administered in elderly patients (>80 years) has a longer onset time compared to younger patients.

Condition or Disease	Intervention/Treatment	Phase
Elective Surgery	Drug: Rocuronium

Detailed Description

The number of elderly patients (>80 years) is increasing and a large proportion of these patients will require surgery and anesthesia within the next decades. Elderly patients are at higher risk of major morbidity and mortality and are characterized by a reduction in cardiac output, liver function and renal function. These physiological changes influence pharmacodynamics and pharmacokinetics of drugs administered during anesthesia as for example neuromuscular blocking agents (NMBA).

During anesthesia NMBAs are used to facilitate tracheal intubation, establish muscle relaxation and suppress reflexes during surgery. Elderly patients are more sensitive towards muscle relaxants. In addition studies have reported prolonged duration of NMBAs and an observational study found that elderly patients are more prone to experience residual neuromuscular blockade in the post anesthesia care unit. However, most studies have been conducted in elderly below 80 years.

It is unknown if there are differences in onset times of NMBAs e.g. rocuronium, mivacurium and cisatracurium between younger patients and elderly. Onset time for NMBAs in the elderly is of importance since it may influence intubating conditions, especially during rapid sequence induction. For example it is unknown in the elderly if an increased dose of NMBA reduces the onset time. There remains a need for studies investigating the optimal dose for facilitating intubation in the elderly, both during rapid sequence induction and during elective procedures.

The aim of this study is to determine the onset time, duration of action and effect on intubating conditions for rocuronium 0.6 mg/kg in patients aged 18-40 years and in patients with age > 80 years. The hypothesis of this study is that rocuronium administered in elderly patients (>80 years) has a longer onset in the elderly compared to younger patients.

Study Design

• Study Type: Observational
• Actual Enrollment: 32 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: An Observational Study of Rocuronium 0.6 mg/kg Comparing Onset Time, Duration of Action and Effect on Intubation Conditions in Younger (18 - 40 Years) and Elderly Patients (> 80 Years)
• Actual Study Start Date: Mar 27, 2019
• Actual Primary Completion Date: Oct 8, 2019
• Actual Study Completion Date: Oct 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Elderly (>80 years) Patients planned for elective surgery above 80 years	Drug: Rocuronium; 0.6 mg/kg; Other Names: Rocuronium 0.6 mg/kg
Younger (18-40 years) Patients planned for elective surgery between 18-40 years	Drug: Rocuronium; 0.6 mg/kg; Other Names: Rocuronium 0.6 mg/kg

Outcome Measures

Primary Outcome Measures

1. Onset Time [Day 0, after induction of anesthesia]

   The time from the end of rocuronium injection to train-of-four (TOF) count of 0 monitored by acceleromyography. The ulnar nerve was stimulated during the monitoring.

Secondary Outcome Measures

1. Comparing Intubating Conditions in the Two Groups [Day 0, after induction of anesthesia]

   90 seconds after induction the conditions are rated by the Intubating Difficulty Scale (IDS). Easy is defined as IDS of 0. Slight is defined as IDS of 1 to 5 Moderate/Major is defined as >5

2. Duration of Action [Day 0, after induction of anesthesia]

   Time from end of rocuronium injection to TOF ratio >0.9. When the ratio between the first and last stimulation in TOF is above 90 %.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients > 18 years old

• Informed consent

• Scheduled for elective surgery (>1 hour) under general anaesthesia with intubation and use of rocuronium.

• American Society of Anaesthesiologists (ASA) physical status classification I to III

• Can read and understand Danish

Exclusion Criteria:

• Known allergy to rocuronium

• Neuromuscular disease that may interfere with neuromuscular data

• Indication for rapid sequence induction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rigshospitalet	Copenhagen		Denmark	2100

Sponsors and Collaborators

• Rigshospitalet, Denmark

Investigators

• Principal Investigator: Matias Vested, MD, Phd, Rigshospitalet, Denmark

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 6, 2018

More Information

Publications

None provided.

• Responsible Party: Matias Vested, Principal Investigator, Medical Doctor, PhD, Rigshospitalet, Denmark
• ClinicalTrials.gov Identifier: NCT03857750
• Other Study ID Numbers: H-18063017
• First Posted: Feb 28, 2019
• Last Update Posted: Jun 2, 2020
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Rocuronium

Study Results

Participant Flow

Recruitment Details	Patients were included from the Departments of Anaesthesia, Centre of Head and Orthopaedics and Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmark in the period of the 27th of March 2019 to 7th of November 2019.
Pre-assignment Detail	Five of 37 patients were excluded due to rescheduling, rapid sequence induction, prone position and different anesthetic medication. 3 patients in each group have missing data on duration of action due to supplementary doses of rocuronium.

Arm/Group Title	Elderly (>80 Years)	Younger (18-40 Years)
Arm/Group Description	16 patients planned for elective surgery above 80 years Rocuronium: 0.6 mg/kg	16 patients planned for elective surgery between 18-40 years Rocuronium: 0.6 mg/kg
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Elderly (>80 Years)	Younger (18-40 Years)	Total
Arm/Group Description	16 patients planned for elective surgery above 80 years Rocuronium: 0.6 mg/kg	16 patients planned for elective surgery between 18-40 years Rocuronium: 0.6 mg/kg	Total of all reporting groups
Overall Participants	16	16	32
Age, Customized (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	84	31	60
Sex: Female, Male (Count of Participants)
Female	13 81.3%	13 81.3%	26 81.3%
Male	3 18.8%	3 18.8%	6 18.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Denmark	16 100%	16 100%	32 100%
Height (centimeters) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [centimeters]	164	174	169
Weight (kilograms) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kilograms]	74	72.5	73.5
ASA (Count of Participants)
ASA I	1 6.3%	6 37.5%	7 21.9%
ASA II	8 50%	9 56.3%	17 53.1%
ASA III	7 43.8%	1 6.3%	8 25%
Comorbidities (participants) [Number]
Heart disease	7 43.8%	1 6.3%	8 25%
Hypertension	13 81.3%	0 0%	13 40.6%
Liver disease	0 0%	1 6.3%	1 3.1%
Renal disease	2 12.5%	0 0%	2 6.3%
Diabetes	3 18.8%	0 0%	3 9.4%
Medication (participants) [Number]
Any	15 93.8%	11 68.8%	26 81.3%
Loop-diuretics or thiazids	8 50%	5 31.3%	13 40.6%
Magnesium	1 6.3%	0 0%	1 3.1%
Duration of anesthesia (minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [minutes]	164	146	154
Duration of surgery (minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [minutes]	104	101	102

Outcome Measures

1. Primary Outcome

Title	Onset Time
Description	The time from the end of rocuronium injection to train-of-four (TOF) count of 0 monitored by acceleromyography. The ulnar nerve was stimulated during the monitoring.
Time Frame	Day 0, after induction of anesthesia

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Elderly (>80 Years)	Younger (18-40 Years)
Arm/Group Description	16 patients planned for elective surgery above 80 years Rocuronium: 0.6 mg/kg	16 patients planned for elective surgery between 18-40 years Rocuronium: 0.6 mg/kg
Measure Participants	16	16
Median (Inter-Quartile Range) [seconds]	135	90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elderly (>80 Years), Younger (18-40 Years)
	Comments	Comparing onset time of rocuronium
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	82
	Confidence Interval	(2-Sided) 95%; 40 to 124
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elderly (>80 Years), Younger (18-40 Years)
	Comments	82
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Mann-Whitney odd
	Comments
Method of Estimation	Estimation Parameter	Odds
	Estimated Value	19.48
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	95 % confidence interval is 7.63 to infinity

2. Secondary Outcome

Title	Comparing Intubating Conditions in the Two Groups
Description	90 seconds after induction the conditions are rated by the Intubating Difficulty Scale (IDS). Easy is defined as IDS of 0. Slight is defined as IDS of 1 to 5 Moderate/Major is defined as >5
Time Frame	Day 0, after induction of anesthesia

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Elderly (>80 Years)	Younger (18-40 Years)
Arm/Group Description	16 patients planned for elective surgery above 80 years Rocuronium: 0.6 mg/kg	16 patients planned for elective surgery between 18-40 years Rocuronium: 0.6 mg/kg
Measure Participants	16	16
Easy	7 43.8%	7 43.8%
Slight	8 50%	9 56.3%
Moderate/Major	1 6.3%	0 0%

3. Secondary Outcome

Title	Duration of Action
Description	Time from end of rocuronium injection to TOF ratio >0.9. When the ratio between the first and last stimulation in TOF is above 90 %.
Time Frame	Day 0, after induction of anesthesia

Outcome Measure Data

Analysis Population Description

3 in each group had missing data due to supplementary doses of rocuronium

Arm/Group Title	Elderly (>80 Years)	Younger (18-40 Years)
Arm/Group Description	16 patients planned for elective surgery above 80 years Rocuronium: 0.6 mg/kg	16 patients planned for elective surgery between 18-40 years Rocuronium: 0.6 mg/kg
Measure Participants	13	13
Median (Inter-Quartile Range) [minutes]	81	53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Elderly (>80 Years), Younger (18-40 Years)
	Comments	Comparing duration of action of rocuronium
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	31
	Confidence Interval	(2-Sided) 95%; 14 to 48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Elderly (>80 Years), Younger (18-40 Years)
	Comments	Comparing duration of action of rocuronium
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wilcoxon Mann-Whitney odd
	Comments
Method of Estimation	Estimation Parameter	Odds
	Estimated Value	6.35
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Confidence interval is 2.59 to infinity.

Adverse Events

Time Frame	From induction of anesthesia to departure from the operating room.
Adverse Event Reporting Description	In both groups the patients will receive rocuronium in a dose aiming to provide optimal intubating conditions. It is not regarded as a disadvantage to use rocuronium, since the effect is monitored through surgery and if needed fully reversed by a reversal agent upon end of surgery. It is an observational study why the patients mortality was not affected by the trial. Furthermore, patients at high risk for serious adverse events were excluded due to the criteria.
Arm/Group Title	Elderly (>80 Years)		Younger (18-40 Years)
Arm/Group Description	16 patients planned for elective surgery above 80 years Rocuronium: 0.6 mg/kg		16 patients planned for elective surgery between 18-40 years Rocuronium: 0.6 mg/kg
All Cause Mortality
	Elderly (>80 Years)		Younger (18-40 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Elderly (>80 Years)		Younger (18-40 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Elderly (>80 Years)		Younger (18-40 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.