Lidocaine as an ETT Cuff Media in the Immediate Post-operative Cardiac Surgery Patient Population, and Its Effect on Sedation/Analgesia Requirements: a Pilot Study
Phase: PHASE2
Conditions: Cardiac Disease
Sponsor: Mayo Clinic

 
 
A Feasibility Study to 
Investigate Lidocaine as an ETT 
Cuff Media in the Cardiac 
Surgery ICU Patient Population, 
and its Effect on Sedation 
Requirements 
 
 
NCT# 03343080 
 
April 23, 2018 

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Title of Study: A FEASIBILITY STUDY TO INVESTIGATE LIDOCAINE AS AN ETT CUFF MEDIA IN THE 
CARDIAC SURGERY ICU PATIENT POPULATION, AND ITS EFFECT ON SEDATION REQUIREMENTS 
Version: 4-23-2018 
Principal Investigator: Troy Seelhammer, M.D. 
Co-Principal Investigators: Erica Wittwer, M.D. 
Co-Investigators: Katelynn Kressin, RN, Ellen Borhart, RN, Jenna Steege, CRNA., Eric DuBois, RN, Marci 
Newcome, APRN.  
Statistician: Darrell Schroeder 
Background and Significance 
Patients who undergo general anesthesia with tracheal intubation frequently suffer from multiple 
adverse events with the endotracheal tube (ETT) itself a frequent source of pain and discomfort.1  
Tracheal mucosal inflammation and irritation caused by the ETT may exacerbate many of these 
symptoms which create a variety of respiratory challenges including difficulty maintaining patient-
ventilator synchrony.   Generally speaking, this problem can be treated with sedation and analgesia 
medications.  These medications however, can subsequently increase the total time of intubation, 
length of intensive care unit (ICU) stay, as well as increase morbidity and mortality.2  
Additionally, other adverse events often occur once the patient is extubated including sore throat, 
cough, restlessness, dysphagia, and dysphonia. When considered in their entirety, these adverse 
events are referred to as, emergence phenomena (EP). 1,3,4  EP can subsequently lead to setbacks 
regarding surgical procedures.  Setbacks arise often due to increases in intra-thoracic or intra-
abdominal pressure, intraocular pressure, and intracranial pressure.  Increases in these various 
pressures may result in post-operative bleeding, bronchospasms, vitreous loss, or possibly wound 
dehiscence.5    
 
 
Pharmacological support includes; NSAIDS, opioids, or sedation and analgesia medications (while 
intubated).  Among these medications, lidocaine has recently been emerging as a superior method of 
choice.5  Recent evidence-based literature (randomized controlled trials [RCTs], systematic reviews, 
Cochrane review, and expert opinion) has shown that lidocaine as an intracuff media for patients who 
are mechanically ventilated, can reduce sedative requirements thereby improving ETT tolerance, and 
can reduce EP.5-8  Reducing sedation may result in: less side effects of the sedation medication, a 
quicker extubation time leading to a shorter stay in the ICU, and a reduction in overall cost. 
 
The proposed study seeks to investigate the efficacy of instillation of buffered lidocaine as an 
endotracheal tube cuff medium on post-operative sedative requirements, time to extubation, and 
frequency of emergence phenomena in a population of adult patients undergoing cardiac surgical 
procedures requiring endotracheal intubation.   
 

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After completion of a thorough review of the current literature, the optimal route for investigating the 
above clinical question is a prospective feasibility study to determine the effect of 1.8% 
lidocaine/0.76% sodium bicarbonate in the ETT cuff for the stated outcomes. The proposed research 
project will be called, the lidocaine project and will be conducted in the cardiac surgery ICU at Saint 
Mary’s Hospital (Mayo Clinic), in Rochester, MN.  This setting is highly desired due to the high volume 
of cardiac surgeries being performed at Mayo Clinic.  This population of patients proves to be 
consistent in their post-operative recovery period and quite often is extubated within 6 hours.  This will 
provide a substantial window of opportunity to study the effects of the intervention.   
 
References 
1. 
Biro P, Seifert B, Pasch T. Complaints of sore throat after tracheal intubation: a prospective 
evaluation. Eur. J. Anaesthesiol. 2005;22(04):307-311. 
2. 
Basuni A. Intracuff alkalized lidocaine reduces sedative/analgesic requirements for mechanically 
ventilated patients. Saudi J. Anaesth. 01 Oct 2014;8(4):451-455. 
3. 
Scuderi PE. Postoperative sore throat: more answers than questions. Anesth. Analg. 
2010;111(4):831-832. 
4. 
Jaensson M, Olowsson LL, Nilsson U. Endotracheal tube size and sore throat following surgery: a 
randomized‐controlled study. Acta Anaesthesiol. Scand. 2010;54(2):147-153. 
5. 
Lam F, Lin Y-C, Tsai H-C, Chen T-L, Tam K-W, Chen C-Y. Effect of Intracuff Lidocaine on 
Postoperative Sore Throat and the Emergence Phenomenon: A Systematic Review and Meta-
Analysis of Randomized Controlled Trials. PloS one. 2015;10(8):e0136184. 
6. 
Mallick A, Smith S, Bodenham A. Local anaesthesia to the airway reduces sedation 
requirements in patients undergoing artificial ventilation. Br. J. Anaesth. 1996;77(6):731-734. 
7. 
Tanaka Y, Nakayama T, Nishimori M, Sato Y, Furuya H. Lidocaine for prevention of a sore throat 
following an operation under general anaesthetic. Health (N. Y). 2007. 
8. 
Altintaş F, Bozkurt P, Kaya G, Akkan G. Lidocaine 10% in the endotracheal tube cuff: blood 
concentrations, haemodynamic and clinical effects. Eur. J. Anaesthesiol. 2000;17(7):436-442. 
9. 
Abbasi A, Mahjobipoor H, Kashefi P, et al. The effect of lidocaine on reducing the tracheal 
mucosal damage following tracheal intubation. J. Res. Med. Sci. 2013;18(9). 
 
Specific Aims 
1. The primary outcome is to determine if 1.8% lidocaine/0.76% Sodium Bicarbonate in the ETT 
cuff will improve ETT tolerance thereby reducing sedation requirements. 
 
2. A secondary outcome is to determine if 1.8% lidocaine/0.76% Sodium Bicarbonate in the ETT 
cuff will decrease the total amount of time the patient requires mechanical ventilation. 
 
3. Secondary outcomes are to determine if 1.8% lidocaine/0.76% Sodium Bicarbonate in the ETT 
cuff decreases post-extubation sore throat, cough, dysphonia, dysphagia, restlessness, and 
agitation.  
 

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Design and recruitment: 
This project will be carried out as a small feasibility study.  It will be carried out in the Cardiovascular 
Surgical Intensive Care Unit (CVSICU) of Saint Mary’s Hospital, in Rochester, MN.  After obtaining 
approval by the Institutional Review Board (IRB), patients will be recruited by the research assistant 
during their initial outpatient appointment for their upcoming cardiac surgical procedure, as well as 
pre-operatively the day of surgery.  Patients who are deemed in the clinic as, “rapid recovery,” meet 
the inclusion criteria, and are expected to require ventilatory support for a period of less than 5 hours 
post-operatively in the cardiac ICU will be enrolled in this small feasibility study.   
 
Inclusion Criteria: 
- 
All patients > 18 years of age (male and female) who will receive general anesthesia for cardiac 
surgery at St. Mary’s Hospital (SMH) in Rochester, MN 
- 
Cardiac surgery includes: single valve repair, myectomy, CABG, pericardectomy.  
- 
Patients who are anticipated  to be deemed, “rapid recovery,”  in the cardiac surgery ICU at St. 
Mary’s Hospital  
- 
 
Exclusion Criteria: 
- 
Age < 18 years old at time of surgery 
- 
Patients who cannot consent themselves or non-English speaking patients who require an 
interpreter  
- 
Patients who are not sent to the cardiac ICU post-operatively 
- 
Patients who are anticipated to have a difficult tracheal intubation 
- 
Patients having risk factors of postoperative aspiration of gastric contents 
- 
Patients who have respiratory disease or recent respiratory tract infection 
- 
> 2 attempts to secure an airway 
- 
Patients undergoing TAVR procedures or any form of “robotic,” procedures 
 
 
Methods: 
Patients will be chosen based on their inclusion/exclusion criteria.  Patients during their clinic 
appointment prior to surgery were provided a thorough explanation of the intervention and study, if 
the patient agrees to participate; he or she will be included in the study.  The day of the procedure, the 
patient will have the intervention take place while in the operating room by the Registered Respiratory 

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Therapist (RRT), Certified Registered Nurse Anesthetist (CRNA) or Anesthesiologist.  The patient will 
remain intubated after the surgery is complete and will be taken to the cardiac surgical ICU.   
 
At the induction of anesthesia, patients will be breathing 100% oxygen via a face mask and then, 
become anesthetized according to a standard protocol and at the discretion of the attending 
anesthesiologist. Patients will be receiving fentanyl, lidocaine (as an IV anesthetic preventing 
uncomfortable side effect Propofol can create in the arm) and either succinylcholine or vecuronium to 
facilitate tracheal intubation. Laryngoscopy will then be performed and the trachea intubated with a 
standard cuffed ETT.  ETT tubes from 6.0mm to 8.0mm in diameter will be used.  Inflation of the ETT 
cuff will be performed in accordance with the randomization of either air or 1.8% lidocaine/0.76% 
solution until such time as there is no air leak around the tube when administering positive pressure to 
20 cm H2O. Checking for intermittent leaks to ensure a minimum seal is present will be done as 
needed per standard of care. Anesthesia will be maintained with volatile anesthetic with or without a 
Propofol infusion.  Vecuronium will be used to maintain the ulnar nerve train-of-four at 0–3 of four 
twitches. Anesthesia maintenance will occur until the near end of the surgical procedure.  The volatile 
anesthetic will be discontinued and Propofol will be initiated via a continuous infusion to facilitate 
transportation to the intensive care unit (ICU).  After arrival to the ICU, Neuromuscular blockade will 
then be antagonized with suggamadex reversal agent, and the pharynx being gently suctioned under 
direct vision. Mechanical ventilation to be maintained until swallowing or spontaneous respiration 
begins, and then, converted to assisted manual ventilation. Extubation will be performed at ICU 
provider’s discretion once the extubation protocol criteria are met.  
The patient then will be closely monitored as a 1:1 by the room nurse, and by other staff (respiratory 
therapist, and ICU fellows and consultants) for toleration of the ventilator (coughing, double triggering, 
“bucking,” etc.) on the cardiac surgical intensive care unit.  Sedation amount will be recorded 
electronically from initiation of the mechanical ventilation weaning protocol until the time of 
extubation.  The RRT will physically record “yes,” or “no,” on the form provided regarding the patient 
coughing, complaining of a sore throat or difficulty swallowing, having hoarseness or difficulty 
speaking.  
 
Sample Size: 
The sample size for this investigation is determined for the primary endpoint of total propofol dose in 
the first 4 hours. Basuni (2014) reported differences in propofol dose of approximately 0.7 SD for 
patients receiving saline vs lidocaine+bicarb. 
 
The current investigation is considered a randomized Phase II study, with the objective of determining 
whether or not additional studies of the current treatment intervention are warranted.  Although 
debate exists regarding the value of formal statistical comparisons in phase II trials, we agree with 
those who propose that a one-sided test with a false-positive (type I error) rate of 0.10 for the primary 
endpoint is an appropriate criterion to use to help guide the decision-making process.  In general, a 
sample-size of N=20 patients per group will provide statistical power (one-tailed, alpha=0.10) of 80% to 
detect a difference between groups of 0.7 standard deviation units. 
 
Data Collection: 

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Regarding the primary outcome, total sedation required from the time of the patient entering the ICU 
until extubation, will be recorded in the electronic charting documentation.   
 
Regarding a secondary outcome, the total amount of time the patient is intubated (from the time they 
enter their room in the ICU from surgery) will be recorded by the RRT on the assessment form 
provided.  
 
Regarding the secondary outcomes, patient assessment forms will be provided in the envelopes 
(attached to patients chart) for the study team, SRNA, to fill out.  Completed assessments will be 
collected at the end of each day and will be manually analyzed at the end of the study once the sample 
size is reached.   
 
Data Analysis 
 
Data will be summarized using mean±SD, or median [25th, 75th] for continuous variables and frequency 
counts and percentages for nominal variables. The primary endpoint will be sedative dose (Propofol, 
precede, fentanyl, ketamine) amount from the mechanical ventilation weaning protocol initiation until 
ETT extubation This endpoint will be compared across groups using the two-sample t-test, or rank sum 
test.   Secondary endpoints will include; time to extubation (from initiation of the mechanical 
ventilation weaning protocol); and coughing, restlessness, hoarseness, and dysphagia.  Sedative dose 
will be treated as continuous variables and analyzed using ANOVA. Post-extubation endpoints will be 
dichotomized and analyzed using logistic regression. In all cases, distributional assumptions will be 
assessed with transformations or nonparametric methods used as appropriate. 
 
Statistical Analysis: 
Recorded characteristics will be presented using mean ± SD or median (IQR) for continuous variables 
and frequency percentages for categorical variables.  Summaries of these variables will be presented 
overall.  The primary outcome will be compared using analysis of variance (ANOVA).  Secondary 
analyses will also be performed and analyzed using logistic regression. Two-tailed p-values ≤ 0.05 will 
be considered statistically significant in all analyses. 
 
Strengths 

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Despite variation in co-morbidities and surgery types, all patients deemed rapid recovery eligible have 
necessarily undergone screening for complications, hemodynamic stability, adequacy of hemostasis, 
and anticipated readiness for extubation within 2 to 6 hours. This improves the generalizability of study 
results. All patients have the added benefit of being closely and safely monitored by the cardiac ICU 
team during the entire duration of the intervention.  There will be a pharmacist on the ICU as well to 
help with any discrepancies that may arise.  The study is using a sample size with sufficient enough 
power to gain a greater separation of results between the control and intervention arms. 
 
Limitations 
Our team acknowledges several limitations.  Only a single lidocaine concentration and a single sodium 
bicarbonate concentration will be studied. Previous studies have compared various concentrations of 
sodium bicarbonate; results have not shown a difference in patient outcomes.  Future projects could 
investigate other instillation solutions to further optimize therapeutic efficacy.  There is data that the 
heart rate can be lower in patients receiving alkalinized lidocaine.  However it is common for 
postoperative cardiac surgical patients to have paced rhythms and vasoactive drug infusions, both of 
which can derange the HR.  HR will not be included as a secondary outcome, however could be 
something to consider in future studies.  Oxygen saturation proves difficult to record as many factors 
can give a false reading (transient face mask, turning up of nasal cannula not often charted), so this 
was left out as a potential secondary outcome.  Hypercarbia could be included in future studies as a 
secondary outcome.  This study left it out because it requires ensuring that a post-extubation arterial 
blood gas is obtained.  This quite often is not reliably obtained nor is the time to obtain the sample 
standardized.  Future research regarding the use of lidocaine as an ETT cuff media could certainly 
entertain the idea of incorporating some of these potentially important outcomes.   
 
 
Budget 
 
After first obtaining IRB approval, funding will be applied for through the Mayo Clinic Center for Clinical 
and Translational Science (CCaTS) 2017 Small Grants Program (SGP) allocation for the Department of 
Anesthesiology. CCaTS Research Resources will assist with the statistical analysis. 
 
Should a poster be generated to disseminate results, under the new institutional guidelines for poster 
development and preparation, Media Support Services will provide support and print the poster at no 
charge.  
 
 
Human Subjects 
 
Description  
This study will be conducted as a feasibility study prospectively comparing a single group of patients 
receiving lidocaine, respectively via the ETT cuff.   
Research Materials: 

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No biological specimens will be obtained.  
 
Confidentiality and Data Management 
The confidentiality of all study participants will be maintained.  After the outcome measures are 
collected, data will be abstracted and entered into an electronic database.  At the time of data entry, 
all personal identifiers will be removed.  When not in use, the electronic database will be securely 
housed in the administrative offices of the Anesthesia Clinical Research Unit.   
 
 
 
 
Informed Consent 
Written informed consent will be obtained from all study participants prior to involvement in the study 
protocol.  All potential study subjects will be told that declining to participate in the research project 
will in no way impact their medical care at Mayo Clinic.   
 
Potential Risks:  
There is an extremely rare chance the ETT cuff could rupture. There has been a recent documented 
incidence however, involving a patient who received an unknown amount of lidocaine in their ETT 
during a non-study, off-label use of lidocaine.  The patient did have a negative outcome regarding vocal 
cord injury, although it should be known that this could have occurred due to a variety of reasons 
ranging from improper ETT placement, coughing, cuff/tube migration, pain/light anesthetic agent, etc.   
In case of ETT cuff rupture, and to avoid potential systemic toxicity, we will be using a dose which is 
well under the toxic level, as documented by previous literature.  Other potential risks are none 
greater that would otherwise normally occur to a typical cardiac surgery ICU patient.   
 
In addition, the potential risks that have been investigated in the literature for this topic are comprised 
of: two meta-analyses, many randomized-controlled trials, and one retrospective case-control study. 
The majority of this evidence is level II, with two level I meta-analysis on the Ackley level of evidence 
scoring tool, indicating a high level of quality, reliability, and generalizability, with a low risk of bias 
among the evidence.1  For over 20 years, researchers have been experimenting with lidocaine to help 
patients overcome the various side effects and complications of being intubated. There have been a 
few studies conducted to determine the safety and efficacy of lidocaine diffusion across the 
polyurethane cuff of the endotracheal tube.2,3 Both Estebe et al.4 and Huang et al.3 determined that 
alkalinization of lidocaine is safe to use, without compromising the integrity of the cuff and improves 
the diffusion when compared to lidocaine alone. Since these studies, most researchers have utilized 
alkalinized lidocaine in intracuff studies, and there have even been a few studies that have compared 
different concentrations of lidocaine.4,5 This high level of evidence will guide a protocol for the 

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anesthesia and intensive care staff at Mayo Clinic caring for rapid recovery cardiac surgery patients. 
This study will improve and elaborate on the science behind intracuff lidocaine and the positive impact 
on lowering patient sedation requirements, as well as, bridge the gap between current studies with 
endotracheal lidocaine and decreased sedation in the intensive care setting. While reviewing the 
literature, there were no reported cases of sentinel events or tube rupture.  
            With the scientific evidence, our team has also consulted with multidisciplinary groups across 
the campus to ensure safety and efficacy of this study. The critical care respiratory therapists group has 
been educated on the science behind this study, and their role in protecting the patient's airway. The 
respiratory therapists will continue to do all of their normal safety assessments, in addition to 
monitoring how much lidocaine is in the cuff upon arrival to the ICU and at extubation to ensure there 
is not over or under inflation. The team has also obtained approval from the Critical Care Service 
consultant group. This group of highly experienced physicians was briefed on the exact procedures that 
will take place throughout this study, including the benefits and potential risks. 
 
 
1. Melnyk BF-O, E. Evidence-Based Practice in Nursing & Healthcare. 3rd ed. Philadelphia, PA: 
Wolters Kluwer Health; 2011. 
2. Estebe JP, Treggiari M, Richebe P, Joffe A, Chevanne F, Le Corre P. In vitro evaluation of 
diffusion of lidocaine and alkalinized lidocaine through the polyurethane membrane of the 
endotracheal tube. Ann Fr Anesth Reanim. 2014;33(4):e73-77. 
3. Huang CJ, Tsai MC, Chen CT, Cheng CR, Wu KH, Wei TT. In vitro diffusion of lidocaine across 
endotracheal tube cuffs. Canadian journal of anaesthesia = Journal canadien d'anesthesie. 
1999;46(1):82-86. 
4. Estebe J-P, Dollo G, Le Corre P, et al. Alkalinization of intracuff lidocaine improves endotracheal 
tube-induced emergence phenomena. Anesthesia & Analgesia. 2002;94(1):227-230. 
5. Soares SMF, Arantes VM, Módolo MP, et al. The effects of tracheal tube cuffs filled with air, 
saline or alkalinised lidocaine on haemodynamic changes and laryngotracheal morbidity in 
children: a randomised, controlled trial. Anaesthesia. 2017;72(4):496-503. 
 
 
Benefits: 
Direct benefits of this study are the potential to decrease the need for sedation and analgesia 
medication in the mechanically ventilated post-op patients.  This would decrease cost, as well as the 
morbidities that go alone with sedation and analgesia medication usage.  Another benefit is the 
decrease in EP symptoms; sore throat, cough, dysphagia, dysphonia, and restlessness.  A decrease in 
these symptoms would make a more comfortable recovery for patients, as well as potential to 

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decrease any hindrance in their recovery, as many of these symptoms can disrupt healing in their 
respective surgical sites.  These outcomes would add to the body of literature.   
Gender/Minority Mix 
Subjects will be eligible for enrollment, regardless of race or gender with distribution reflecting the 
practice at Mayo Rochester.