Pain, Postoperative Clinical Trial
Official title:
Effects of Local Anaesthetic Infusion Rates on Nerve Block Duration. A Randomised, Blinded, Healthy Volunteer Study
This trial is a part of the project: 'A novel technique for reliable, precise and safe
postoperative pain management' (project no. 65-2014-3).
The purpose of the trial is to investigate the effects of changing peri-neural infusion
rates of ropivacaine 0.2% on the duration of nerve block.
Intervention:
Two intervention-days. Each day a peri-neural infusion of a fixed volume of ropivacaine 0.2%
is to be infused in one of five infusion rates, using a peri-neural catheter.
Intervention day 1: Focus on the common peroneal nerve. Intervention day 2: Focus on the
sciatic nerve.
This trial is a part of the project: 'A novel technique for reliable, precise and safe
postoperative pain management' (project no. 65-2014-3). Results will contribute to the
development of an electrical disposable infusion pump manufactured by Ferrosan Medical
Devices (FEMD). It is made up of two half's; first intervening day focuses on the common
peroneal nerve, second intervening day focuses on the sciatic nerve.
Hypothesis:
The infusion rate of a single peri-neural injection of LA does not influence the duration of
lower limb nerve blocks.
Trial objective:
We wish to compare five peri-neural infusion rates of LA as an independent factor of the
duration of the nerve block, in the sciatic nerve and the common peroneal nerve, in healthy
volunteers.
The slowest infusion will simulate a standard infusion rate for continuous infusion. The
fastest infusion will simulate a standard bolus rate when administering a LA bolus. The
three infusions in between are to our knowledge new alternative infusion rates.
Trial design:
Prospective, randomised, blinded, single centre, healthy volunteer study.
Intervention medication:
Ropivacaine 0.2%
Detailed description of the intervention:
Baseline measurements and safety precautions The volunteers will meet at the Clinical
Research Unit, Nordsjællands Hospital Hillerød, following a six-hour fast. After baseline
measurements, we will insert a peripheral intravenous catheter and start continuous pulse
oximetry.
Placing the catheters
We will insert one peri-neural catheter at each of the intervention days:
1. Adjacent to common peroneal nerve on the non-dominant side. The participant will be
supine on the dominant side.
2. Adjacent to the proximal part of the sciatic nerve on the non-dominant side. The
participant will be in prone position.
An expert in peripheral nerve blocks will perform catheter placement in a sterile manner,
using an ultrasound (US) guided short-axis, needle in-plane technique and a high frequency
linear transducer.
Using lidocaine 1% we will raise a small skin wheal at the needle entry point and
anaesthetise the trajectory of the catheter needle.
3 mL of isotonic saline will be deposited in the peri-neural tissue before placing the
catheter. This ensures optimal conditions for placing the nerve catheters.
Successful catheter orifice placement will be ensured by visually confirmation of the
echogenic markings of the catheter and a 2 mL isotonic saline injection through the orifice.
After insertion, a sterile dressing will be placed, covering the catheters. Absorption from
the peri-neural space We will verify full absorption of the isotonic saline in the
peri-neural space by US. When full absorption is confirmed, members of the investigator team
must leave the room.
Preparation for infusion A trial-affiliated nurse that is not part of the investigator team
will prepare one 50 ml syringe, imbibing 30 mL of ropivacaine 0.5%. This step will be
over-looked by a random, un-affiliated college to ensure double-control of correct
intervention.
Peri-neural infusions
The trial-affiliated nurse will connect a transfusion hose and mount the syringe in the
infusion pump. The nurse will activate a 2 mL bolus on the infusion pump, flushing the
transfusion hose and then connect the transfusion hose to the nerve catheter. The
trial-affiliated nurse will open the opaque envelope that matches the participant and
prepare the infusion and administration as prescribed according to one of the five infusion
groups:
Infusion Groups and Infusion rates [mL/hour] / [mL/min] IG1 12 / 0.2 IG2 60 / 1 IG3 300 / 5
IG4 600 / 10 IG5 1800 / 30
This step will be over-looked by a random, un-affiliated college to ensure double-control of
correct intervention.
The trial-affiliated nurse will start the infusion and the investigator team is allowed back
in.
Measuring outcomes
The outcomes will be measured in the following way:
1. Measuring length of neural exposure to ropivacaine five times, according to calculated
infusion time.
2. Finding sensory onset time by five minutes intervals.
3. Grading the degree of sensory nerve block after registered onset time.
4. Grading the degree of motor nerve block after the catheter has been removed.
Investigators will start testing for sensory onset time 10 minutes after start of
infusion.
All outcomes and outcome measurements are described in detail in the section "Outcomes".
To ensure that manipulation of the catheter will not affect the distribution and absorption
of LA, the catheters will not be removed until 30 minutes after end of the slowest infusion.
We estimate the mean and maximal duration of the sciatic nerve block to be seventeen and
twenty-four hours, respectively15,20-24. Consequently, the duration of each study day is
expected to be no more than twenty-four hours. The volunteer will be offered discharge at
the time of complete nerve block remission. In exceptional cases of incomplete nerve block
remission within twenty-four hours, the volunteer will be asked to stay admitted for
continued testing.
At all times, adequately trained health-care personnel with rescue medicine and
resuscitation equipment at hand will be in proximity to the volunteer.
Intervention related information
- Members of the investigator team who are medical doctors and skilled in performing
US-guided peripheral nerve blocks will insert the peripheral nerve catheters.
- The Certa Catheterâ„¢ will be used as recommended by the manufacturer.
- Study medications as well as medications used for concomitant care will be handled
according to local guidelines and provided and stored by The Department of
Anaesthesiology and Intensive Care, Nordsjællands Hospital Hillerød via the hospital
pharmacy until its use. During the study period, once a week, medications will be taken
from the locked storage of the Post Anaesthesia Care Unit to the locked storage of the
Clinical Research Unit, Nordsjællands Hospital Hillerød.
- All personnel involved in conduction of the intervention is adequately educated and
experienced in performing basal resuscitation.
Discontinuance
The intervention will be discontinued if:
- the participant withdraws consent.
- the participant experiences symptoms of LA systemic toxicity.
- the participant exhibits symptoms of an allergic reaction.
- there is any suspicion of nerve injury In addition to these specific reasons, adverse
reactions of any severity and lack of compliance to instructions may cause
discontinuance.
Concomitant care
1. Sedation If indicated, investigators will administer midazolam (0.03 mg/kg).
2. Treatment of pain Skin infiltration anaesthesia will be necessary when inserting the
catheters the investigator will administer a maximum of 2 mL of lidocaine 1 mg/mL as a
subcutaneous papilla, ensuring non-influential proximity to the sciatic nerve. If the
participant experiences unbearable pain during insertion of the catheters
administration of a standard short acting, intravenous analgesic (0.5-1.5 mg of Rapifen
depending on weight, age and administration and sedation) will be allowed.
3. General care During the trial day the participant will receive meals, snacks and tap
water. The participant will have a bed available at all times, placed in a two-person
room.
Sample size:
To be able to detect a difference with a power of 80% and a margin of error of 5%, when
testing our null-hypothesis, we need the participant number in each infusion group to be
larger than 10.9. Thus, each infusion group will have at least 11 participants, making the
sample size for each intervention-day at least 55 and the total sample size at least 110. To
account for potential dropouts, we wish to include 60 healthy volunteers for each
intervention-day, totalling 120 healthy volunteers.
Sequence generation:
all study numbers will be block-randomised electronically by a non-trial-affiliated person
to one of the five equally sized infusion groups of the first intervention day. This step
will be repeated before the second intervention day.
Allocation concealment mechanism:
Until study termination of FIPRA 1, allocation sequence will be concealed to the
investigator team and noted electronically on a computer belonging to the Research Unit,
Department of Anaesthesiology and Intensive Care, Nordsjællands Hospital Hillerød.
Blinding:
All volunteers and outcome assessors will be blinded to the LA administration and infusion
procedures.
Harms Unanticipated problems involving risks to subjects or others, adverse events and
adverse reactions will be reviewed and reported in accordance to the current thinking by The
Danish Unit for Good Clinical Practice and The Danish Medicines Agency. The reporting will
happen within the timeframe stated by the order of clinical trials with drugs on human
subjects (order #295 of 26th of April 2004 in The Danish Law)
Research ethics approval This trial will be conducted according to guidelines provided by
The International Council for Harmonisation (ICH), The Danish Unit for Good Clinical
Practice (GCP) and The Declaration of Helsinki3. We will register/announce the study at The
Scientific Ethics Committee, The Danish Health and Medicines Authority, The Danish Data
Protection Agency, The Danish Unit for Good Clinical Practice and at clinicaltrials.gov. The
trial is initiated after all official approvals have been given.
Access to data During the trial only the investigators will have access to CRFs and the raw
data material. After the trial the primary investigator, sponsor and supervisor will have
access to the full trial dataset.
The data will be stored for 5 years by The Research Unit, Department of Anaesthesiology and
Intensive Care, Nordsjællands Hospital Hillerød.
As part of the Co-funding agreement between Innovation Fund Denmark, NOH and FEMD (Journal
no. 65-2014-3), results from this study will contribute to the development of an electronic
disposable infusion pump manufactured by FEMD. Furthermore, before publishing, FEMD, has the
right to review the manuscript to ensure that no intellectual properties (IP's) belonging to
FEMD are published. If so, FEMD may claim additional thirty days before submission to apply
for new patent or other protection of IP. FEMD is not allowed to comment or change any other
parts of the manuscript.
The Research Unit, Department of Anaesthesiology and Intensive Care, NOH retains ownership
of all raw clinical data and may use data as they see fit.
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