Efficacy of Intercostal CryoAnalgesia in Patients Undergoing Robot Assisted Anatomic Lung Resection
Phase: PHASE4
Conditions: Pain, Postoperative, Lung Diseases
Sponsor: Medical College of Wisconsin

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Efficacy of Intercostal CryoAnalgesia in Patients Undergoing Robot Assisted 
Anatomic Lung Resection 
 
PROTOCOL SUMMARY 
Synopsis 
Title: 
Efficacy of Intercostal CryoAnalgesia in Patients Undergoing Robot 
Assisted Anatomic Lung Resection 
Short Title: 
CryoNB in Robotic Lung Resection 
Study Design: 
Prospective randomized study 
Study Objectives: 
The objectives are to determine if the addition of Cryo Nerve Block at the 
time of robot assisted thoracoscopic lung resection surgery will: 
• 
Allow for improved postoperative analgesia as measured using 
Visual Analogue Scale (VAS) pain scores 
• 
Allow for decreased post-operative pain medication (opioid) use 
• 
Allow for accelerated recovery as measured by patient reported 
M.D. Anderson Symptom Inventory (MDASI) Questionnaire 
• 
Increases the risk for development of neurogenic pain as 
measured by the Leeds Assessment of Neuropathic Symptoms 
and Signs (LANSS) pain scale 
Number of Subjects: 
40 (20 in each group) 
Sites: 
Single site – Froedtert Hospital/Medical College of Wisconsin 
Single surgeon – Mario Gasparri, MD 
Study Population: 
Patients undergoing robot assisted thoracoscopic anatomic lung 
resection (pneumonectomy, bilobectomy, lobectomy or segmentectomy) 
Inclusion Criteria: 
• 
Age 18 - 85 years male or female 
• 
Acceptable surgical candidate 
• 
Willing and able to return for scheduled follow-up visits 
Exclusion Criteria: 
• 
Patients undergoing or requiring conversion to thoracotomy 
• 
Patients with chronic pain syndromes requiring treatment within 
the last year 
• 
Patients with a history of illicit drug use 
• 
Patients with a history of heavy alcohol use in the last five years 
as determined by the principal investigator 
• 
Patients currently using opioids 
Participant Duration: 
Six months 
Study Endpoints: 
Primary endpoints 
• 
Visual Analogue Scale (VAS) Pain score on post-operative days 
1-14, Day 30, Day 60, Day 90, Day 120, Day 150, Day 180 (or 
until a score of 0). 
• 
Pain medication use daily for 21 days post-operatively 
Secondary endpoints 
• 
M.D. Anderson Symptom Inventory Questionnaire on post-
operative Day 1, Day 7, Day 14, Day 21, Day 30, Day 35, and 
Day 42 
• 
Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) 
score at Post-Operative Day 30, Day 90, and Day 180 
 
 
 
 

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Schema 
 
 
 
 
 
Exclusion 
• 
Chronic pain syndrome requiring 
treatment in the last year 
• 
History of illicit drug use 
• 
History of heavy alcohol use 
within the last five years 
• 
Currently on opioids 
PreOp measures 
• 
Demographics 
• 
Ht/Wt/PFTs… 
• 
Baseline VAS Score 
• 
Baseline MDASI Questionnaire 
• 
Baseline LANSS Score 
To OR 
Intraoperative Nerve Block nerves 4-9 
• 
0.5% Marcaine with Epinephrine 
• 
CryoNb nerves 4-9 
Intraoperative Nerve Block nerves 4-9 
• 
0.5% Marcaine with Epinephrine 
Standard postoperative pain med regimen 
• 
Tylenol 650 mg orally every 6 hours 
• 
Robaxin 500 mg every 6 hours 
• 
Ultram 25-50 mg  every 6 hours as 
needed (prn) 
• 
Oxycodone 5-10 mg every 6 hours 
as needed (prn) 
Outcome measures 
• 
VAS pain scores daily x 14 days then monthly x 6 months (or until 
score of 0) 
• 
Pain medication (opioid) usage daily x 21 days 
• 
MDASI questionnaire on POD 1 then weekly x 6 weeks 
• 
LANSS score at 1 month, 3 months, 6 months 
PostOp measures 
• 
Length of stay (LOS), Chest tube 
duration 
• 
Complications 
IntraOp measures 
• 
Procedure 
• 
Duration of OR time 
• 
Port Placement 
• 
Estimated blood loss (EBL) 
All patients undergoing robotic anatomic lung resection 
(pneumonectomy, bilobectomy, lobectomy, segmentectomy) 

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HYPOTHESIS 
The addition of Cryo Nerve Block to a standard postoperative pain regimen will improve 
analgesia and facilitate recovery following robot assisted thoracoscopic anatomic lung resection 
 
SPECIFIC AIMS 
This study will determine if the addition of Cryo Nerve Block during robot assisted thoracoscopic 
anatomic lung resection surgery will: 
PRIMARY ENDPOINTS: 
• 
Allow for improved postoperative analgesia as measured using Visual Analogue Scale 
(VAS) pain scores 
• 
Allow for decreased post-operative pain medication (opioid) usage 
SECONDARY ENDPOINTS: 
• 
Allow for accelerated recovery as measured by patient reported M.D. Anderson 
Symptom Inventory (MDASI) Questionnaire 
• 
Increases the risk for development of neurogenic pain as measured by the Leeds 
Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale 
 
RATIONALE FOR THE PROJECT 
Thoracic surgical procedures are consistently reported to be among the most painful surgical 
incisions currently used.1  Trauma to the skin, muscle, intercostal nerves, bones and pleura all 
contribute and lead to activation of various pain pathways including somatic, visceral, 
neurogenic and phrenic.1  In the short term, this pain leads to ineffective cough and pulmonary 
hygiene resulting in respiratory complications and prolonged hospital stays while in the longer 
term it leads to prolonged recovery, delayed return to work and in some instances, chronic post 
thoracotomy pain syndromes.2  Minimally invasive approaches such as standard thoracoscopy 
or robotic assisted thoracoscopy have certainly decreased some of this trauma as evidenced by 
decreased length of stays and decreased complication rates however even with these minimally 
invasive techniques, recovery to 80% of baseline is 25 days3 and 9.4% of patients are still using 
narcotics after 90-180 days.4   
 
Several options are available in the management of pain following thoracic surgery with a 
multimodal pain medicine approach being most common.  Opioids, unfortunately, are a 
relatively large part of this approach and are often relied upon despite their relatively 
unfavorable adverse event profile and risk for addiction. Many of the other pain adjuncts often 
used with thoracotomies such as epidural catheters or intraoperatively placed pain catheters are 
not really reasonable when using minimally invasive approaches as the hospital length of stay is 
1-2 days. Intercostal cryoanalgesia has been shown to be a safe and effective strategy for post-
operative pain management in patients undergoing thoracotomy.5,6  Recent studies have 
demonstrated the beneficial effect of cryoanalgesia for post-thoracotomy pain in reduction of 
opioid requirement, reduction in post-operative pain scores, and superior pulmonary function 
(higher FEV1 and FVC values)5 and that it can produce temporary neurolysis for up to two 
months without long-term histological nerve damage.6  To date it has not been studied when 
using minimally invasive techniques whether it be standard thoracoscopy or robotic assisted 
thoracoscopy but it would stand to reason that it would be equally or maybe more effective in 
this patient population and truly maximize the benefits of a minimally invasive approach . 
 
We therefore propose to assess whether intra-operative intercostal cryoanalgesia using the 
cryoICE® probe provides superior post-operative analgesia as compared to our current 
standard pain management strategy in patients undergoing robotic assisted thoracoscopic 
anatomic lung resection and allows for decreased opioid use and more rapid recovery. 

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PROJECT DESIGN AND PROTOCOL 
DESIGN 
This is a single center, single surgeon, prospective, randomized trial examining the addition of 
Cryo Nerve Block during robot assisted thoracoscopic anatomic lung resection surgery 
 
SUBJECTS IN THE STUDY 
40 total subjects will be enrolled in the study – 20 in each group 
Inclusion Criteria 
• 
Patients undergoing robot assisted thoracoscopic anatomic lung resection surgery 
• 
Male or female age 18 or older 
• 
Acceptable surgical candidate 
• 
Willing and able to return for scheduled follow-up visits 
Exclusion Criteria 
• 
Patients undergoing or requiring conversion to thoracotomy 
• 
Patients with chronic pain syndromes requiring treatment in the last year 
• 
Patients with a history of illicit drug use 
• 
Patients with a history of heavy alcohol use in the last five years as determined by the 
principal investigator 
• 
Patients currently using opioids 
 
CONSENT 
All patients eligible for this study will be approached for consent to enter the study in compliance 
with Human Research Review Committee (HRRC) standards.  Consent will be obtained by the 
principal investigator or authorized delegate. 
 
RANDOMIZATION PROCESS 
Following the attainment of consent to enter the study, patients will be randomized to either the 
standard postoperative pain regimen or the standard postoperative pain regimen plus cryo 
nerve block by a blinded procedure where a card indicating either group will be drawn in a 
witnessed setting by a noninvestigator. 
  
PROCEDURE 
All patients will be assessed at baseline and then taken to the operating room for robot assisted 
thoracoscopic anatomic lung resection surgery.  Each operation will be performed by the same 
surgeon and port placement will be identical (aside from laterality) in each patient.  All patients 
will have the first two ports placed at which time an intercostal nerve block of nerves 4-9 will be 
performed using 0.5% Marcaine with Epinephrine.  Additionally, in the study group, Cryo Nerve 
Block of nerves 4-9 will also be performed.  To perform the cryo nerve block the 18 inch 
Atricure® cryoSPHERE Probe will be used in each case.  The remaining ports will then be 
placed, the robot docked, and the procedure performed.  Following the procedure, a chest tube 
will be placed through the camera port.  Postoperatively, all patients will receive the standard 
post-operative pain regimen currently used by the Thoracic Surgery Service at Froedtert 
Hospital/Medical College of Wisconsin which consists of Tylenol and Robaxin around the clock 
and Ultram as first line analgesia for breakthrough pain and Oxycodone as the second line 
agent if necessary. 
 
RISKS AND PRECAUTIONS 
The pain management strategy outlined above, whether with or without cryo nerve block, is the 
current standard pain management strategy following robot assisted thoracoscopic lung 

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resection surgery at Froedtert Hospital/Medical College of Wisconsin. Both are routinely 
employed and it must be stressed that neither arm is experimental in any way with both 
modalities currently in use and being used successfully.  What is unclear at present is which 
approach offers greater advantage to the patient in terms of improved analgesia and facilitation 
of recovery. 
 
Risks inherent to this study are those associated with the operative procedure of robot assisted 
thoracoscopic lung resection surgery.  To date there have been no reports of acute adverse 
events with cryo nerve block. 
 
DATA COLLECTED 
As shown in the schema, the following data will be collected 
 
Preoperatively – within 30 days of surgery 
• 
Characteristics (Age, gender, race, marital status, ECOG function, height, weight, BMI, 
tobacco use, major comorbidities) 
• 
Baseline VAS Score 
• 
Baseline MDASI 
• 
Baseline LANSS 
 
Intraoperatively – at time of surgery 
• 
Procedure 
• 
Procedure duration 
• 
Port placement 
• 
Intraoperative complications 
• 
Estimated blood loss (EBL) 
 
Postoperatively – at designated time points 
• 
Length of stay 
• 
Chest tube duration 
• 
Complications 
• 
VAS pain scores daily on post-operative Days 1-14, Day 30, Day 60, Day 90, Day 120, 
Day 150, Day 180 (or until score of 0). 
• 
Pain med usage daily for post-operative Days 1-21 
• 
MDASI questionnaire on post-operative Day 1, Day 7, Day 14, Day 21, Day 30, Day 35, 
and Day 42 
• 
LANSS score at at Day 30, Day 90 and Day 180 
 
A time frame of data collection points is shown below and the VAS scale, MDASI Questionnaire, 
and LANSS pain scale are included in the appendix. 
 
Day 
Characteristics VAS MDASI LANSS Pain meds 
Baseline 
X 
X 
X 
X 
X 
0 
1 
X 
X 
X 
2 
X 
X 
3 
X 
X 
4 
X 
X 

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5 
X 
X 
6 
X 
X 
7 
X 
X 
X 
8 
X 
X 
9 
X 
X 
10 
X 
X 
11 
X 
X 
12 
X 
X 
13 
X 
X 
14 
X 
X 
X 
15 
X 
16 
X 
17 
X 
18 
 
 
 
 
X 
19 
X 
20 
X 
21 
X 
X 
22 
 
 
 
 
X 
30   (+/- 2 days) 
X 
X 
X 
35   (+/- 2 days) 
X 
42   (+/- 2 days) 
X 
60   (+/- 5 days) 
X 
90   (+/- 5 days) 
X 
X 
120 (+/- 5 days) 
X 
150 (+/- 5 days) 
X 
180 (+/- 5 days) 
X 
X 
 
 
REFERENCES 
 
1. 
Marshall K, McLaughlin K.  Pain Management in Thoracic Surgery.  Thorac Surg Clin 
2020;30(3):339-346 
 
2. 
Niraj G, Kelkar A, Kaushik V, et al.  Audit of postoperative pain management after open 
thoracotomy and the incidence of chronic postthoracotomy pain in more than 500 patients at a 
tertiary center.  J Clin Anes 2017;36:174-177 
 
3. 
Fagundes CP, Shi Q, Vaporciyan AA, et al.  Symptom recovery after thoracic surgery: 
Measuring patient-reported outcomes with the MD Anderson Symptom Inventory.  J Thorac 
Cardiovasc Surg 2015;150:613-9 
 
4. 
Brescia AA, Harrington CA, Mazurek AA, et al.  Factors associated with new persistent 
opioid usage after lung resection.  Ann Thorac Surg 2019;107(2):363–868 
 
 

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5. 
Sepsas E, Misthos P, Anagnostopulu M, et al.  The role of intercostal cryoanalgesia in 
post-thoracotomy analgesia. Interact Cardiovasc Thorac Surg 2013;16:814-818 
 
6. 
Moorjani N, Zhao F, Tian Y, et al.  Effects of cryoanalgesia on post-thoracotomy pain 
and on the structure of intercostal nerves: a human prospective randomized trial and a 
histological study.  Eur J Cardiothorac Surg 2001;20:502-507. 
 
 

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APPENDIX I - Eastern Cooperative Oncology Group (ECOG) Performance Status 
 
 
GRADE 
ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities; up and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or 
chair 
5 
Dead 
 
 
 

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APPENDIX II – Visual Analogue Scale Pain Score 
 
 
 
 
 
 
 
 

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Appendix III – MD Anderson Symptom Inventory (MDASI) Questionnaire 
 
 
 

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Appendix IV – Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale