Journal of Pediatric Surgery 52 (2017) 920–924

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Journal of Pediatric Surgery

journal homepage: www.elsevier.com/locate/jpedsurg

Intraoperative cryoanalgesia for managing pain after the Nuss procedure

Claire Graves a, Olajire Idowu a, Sang Lee b, Benjamin Padilla a, Sunghoon Kim a,⁎
a
Division of Pediatric Surgery, UCSF Benioff Children's Hospitals, Oakland and San Francisco, CA
b
Department of Cardiothoracic Surgery, Regional Medical Center, San Jose, CA

a r t i c l e i n f o a b s t r a c t

Article history: Background: Cryoanalgesia prevents pain by freezing the affected peripheral nerve. We report the use of intraop-
Received 21 February 2017 erative cryoanalgesia during the Nuss procedure for pectus excavatum and describe our initial experience, mod-
Accepted 9 March 2017 ifications of technique, and lessons learned.
Materials and methods: We retrospectively reviewed the medical records of patients who received cryoanalgesia
Key words: during the Nuss procedure between June 1, 2015, and April 30, 2016, at our institutions and analyzed modifica-
Pectus excavatum
tions in surgical technique during this early adoption period.
Cryoanalgesia
Epidural analgesia
Results: Eight male and two female patients underwent the Nuss procedure with cryoanalgesia. The mean post-
Nuss procedure operative length of stay (LOS) was 2 days (range 1–3). Average inpatient pain scores were 3.4, 3.2, and 4.6 on
Cryoprobe postoperative days 1–3, respectively (N = 10, 7, and 2). At a 1-week postoperative visit, mean pain score was
1.1 (N = 6). Compared to the preceding 15 Nuss patients at our institution, who were treated with a thoracic epi-
dural, postoperative LOS was significantly shorter with cryoanalgesia (2.0 ± 0.82 vs. 6.3 ± 1.3 days, P b 0.001).
We modified our technique for patient habitus and adopted single-lung ventilation for improved visualization.
Conclusions: Cryoanalgesia may be the ideal pain management strategy for Nuss patients because it is effective
and long lasting. Intraoperative application is easily integrated into the Nuss procedure.
Study type: Treatment study: case series; Evidence level IV.
© 2017 Elsevier Inc. All rights reserved.

The Nuss procedure has become a common thoracoscopic corrective
operation for pectus excavatum since it was introduced in 1997. The
benefits compared to open repair include smaller incisions, no cartilage
resection or osteotomy, and reduced operative time [1]. However, the
procedure causes significant and lengthy postoperative pain, which
may last for weeks, causing distress for patients, families, and clinicians
[2,3]. There is no standardized optimal pain management following this
procedure. Epidural analgesia and patient controlled analgesia (PCA)
are the two most commonly used techniques, employed either inde-
pendently or together [2–5]. Thoracic epidural analgesia has been
shown to be more effective than PCA alone in the early postoperative
period, but it carries significant risks, including nerve damage leading
to paralysis, infection, and respiratory depression [3,6]. Moreover, the
use of epidural analgesia is limited to the first two to three postopera-
tive days; thereafter, the patient is usually transitioned to oral regimens
[7]. The ability to adequately control postoperative pain is the primary
determinant of hospital stay following the Nuss procedure and often ne-
cessitates a prolonged hospitalization [4].
We recently began performing intraoperative cryoanalgesia during
the Nuss procedure as a new pain control strategy and published the
method of this technique [8]. In this retrospective review, we further
⁎ Corresponding author at: UCSF Benioff Children's Hospitals, 744 52nd Street, Suite
4100, Oakland, CA 94609. Tel.: +1 925 813 4743.
E-mail address: skim@mail.cho.org (S. Kim).
describe the thoracoscopic intrathoracic cryoanalgesia technique, re-
port our experience from treating our first 10 patients, and discuss les-
sons learned thus far.
1. Materials and methods
With approval from institutional review boards at two UCSF Benioff
Children's Hospital campuses (IRB #16-19217 and IRB #150914), we
conducted a retrospective chart review of patients who underwent
the Nuss procedure with cryoanalgesia between June 1, 2015 and
April 30, 2016 at our institutions. All procedures were performed by
one of two attending pediatric surgeons. The first six cases were
performed with single lumen endotracheal intubation, and the remain-
ing four cases were performed with double lumen endotracheal tubes.
All skin incisions made on the chest during the course of the operations
were injected with 0.25% bupivacaine prior to incision. The technical
details of the Nuss procedure we utilized have been described previous-
ly [9].
1.1. Cryoanalgesia application
Cryoanalgesia of the intercostal nerves was performed prior to Nuss
bar placement through a thoracoscopic approach under direct visualiza-
tion with a cryoprobe (cryoICE: AtriCure, Inc., West Chester, OH, USA) in
all patients. After bilateral thoracoscopic port placements, the patient's

http://dx.doi.org/10.1016/j.jpedsurg.2017.03.006
0022-3468/© 2017 Elsevier Inc. All rights reserved.
 C. Graves et al. / Journal of Pediatric Surgery 52 (2017) 920–924 921

Table 1
Characteristics of Patients who Received Intraoperative Cryoanalgesia During the Nuss
Procedure for Pectus Excavatum.

Age Haller Postoperative. Length Length of follow-up

Patient (years) Sex Index of Stay (days) (months)

1 18 M 4 2 12
2 23 F 5.2 3 9
3 31 M 3.3 2 8
4 14 M 5 2 8
5 13 M 3.4 1 8
6 16 M 8 2 8
7 13 M 4.1 2 8
8 16 F 4.3 3 5
9 9 M 6.2 1 6
10 15 M 4 1 4

Fig. 1. Cryoprobe Application: The cryoprobe is placed at 90 degrees to the intercostal
nerve under direct thoracoscopic vision.
anterior sunken chest wall was elevated using the T-fastener suture
technique [9]. The retrosternal space was dissected under direct camera
visualization from the left chest toward the right chest to create a com-
municating channel between the two sides. Once this retrosternal chan-
nel was created, the cryoprobe was placed through the skin incision that
had already been made for inserting the Nuss bar. Next, a rigid 30°
thoracoscope and the cryoprobe were passed together across the ante-
rior mediastinum to gain access to the contralateral chest wall [8]. The
mediastinal tissue is protected from injury by the insulating plastic
sheath, which covers the shaft of the probe. In the few cases where
the patient's chest was too wide for the cryoprobe to reach the contra-
lateral chest wall, the cryoprobe was passed through the ipsilateral
Nuss bar incision site and angled posteriorly in order to access the inter-
costal nerves.
In all patients, 4–5 nerves on each side were treated, proximal (pos-
terior–lateral) to the chest incision site: the intercostal nerve at the level
of the bar insertion, the 2 nerves above, and 2 nerves below. At each
level, the probe was placed in direct contact with the nerve at each rib
space and continuously treated at −60 °C for 2 min (Fig. 1). After the
freeze cycle, the probe was thawed and allowed to fall off the pleural lin-
ing without traction; the thaw cycle was completed within a few
seconds.
1.2. Postoperative care
2. Results
Patient information is summarized in Table 1. Eight male and two fe-
male patients underwent the Nuss procedure with cryoanalgesia. The
mean age was 16.8 years (range 9–31 years). The mean Haller Index
was 4.39 (range 3.2–8). The mean postoperative length of stay (LOS)
was 2 days (range 1–3). Compared to the preceding 15 Nuss patients
at our institution, who were treated with a thoracic epidural, mean
LOS was significantly shorter with cryoanalgesia, 2.0 ± 0.82 vs. 6.3 ±
1.3 days, P b 0.001 (Fig. 2).
Using a verbal pain scale of 0–10, average pain score on postopera-
tive day (POD) 1 was 3.4 (range 1–7). Three patients were discharged
on POD 1. Average pain score of the remaining 7 patients on POD 2
was 3.2 (range 1–5), and of the two patients who stayed until POD 3,
the average pain score was 4.6 (4 and 5.2). Numerical pain scores
were collected for 6 patients at their 1-week postoperative visit, and
mean pain score was 1.1 (range 0–2) (Fig. 3). Length of follow-up
ranged from 4 to 12 months (average 8 months). At the 2-week postop-
erative visit, patient 2, a 23 year-old female, was found to have symp-
tomatic pleural effusions, which required bilateral pigtail placement
for drainage. She also reported a stinging sensation in the anterior
chest one month following the Nuss procedure, which resolved with
gabapentin medication. There were no other immediate postoperative
complications.
Sensation returned gradually in all patients, progressing from lateral
to medial. Normal sensation returned to 5 patients by 2 months after
surgery, 1 patient by 3 months, and 2 patients by 4 months. Two pa-
tients had some persistent numbness at 8 and 9 months, respectively —

Postoperatively, patients were admitted to the postanalgesia care

unit, then to a regular hospital room. No epidurals were placed. Patients
were allowed to have intravenous morphine or oral narcotic (acetamin-
ophen/hydrocodone) as needed. Verbal pain scores were collected by
nurses and physicians and recorded in the electronic medical record.
After hospital discharge, patients presented for postoperative clinic
visits 1–2 weeks after surgery, then 2–3 months after surgery, according
to patient and physician preference. Further in-person follow-up
depended on patient need; otherwise patients were contacted via
phone or e-mail at time of manuscript preparation.

1.3. Data analysis

All data were recorded using Microsoft Excel for Mac 2011
(Microsoft Corporation, Redmond, WA) and analyzed with GraphPad
Prism 7 (GraphPad Software, La Jolla, CA). Basic patient characteristics
were summarized and described. Postoperative length of hospital stay
of the 10 patients who had cryoanalgesia was compared to the length
of stay of the cohort of previous 15 Nuss procedure patients at our insti-
Fig. 2. Postoperative Length of Stay: Mean postoperative length of stay was significantly
tution using the unpaired t test. Verbal pain scores were summarized shorter in patients with cryoanalgesia (N = 10) than in a previous cohort treated with
and described. When more than one pain score was collected from a pa- thoracic epidural (N = 15), 2.0 ± 0.82 vs. 6.3 ± 1.3 days, P b 0.001 (unpaired t test;
tient over a single hospital day, that day's scores were averaged. error bars indicate standard deviation).
922 C. Graves et al. / Journal of Pediatric Surgery 52 (2017) 920–924
Fig. 3. Pain Scores: Numerical pain scores based on a verbal pain score (0–10) on each in-
hospital postoperative day. Pain scores were also collected from six patients seen in
follow-up 1 week after surgery. Horizontal lines indicate mean and standard deviation.
in one patient, of nipples and sternum, and in the other, central sternum
only. Neither patient was bothered by the lack of sensation. Two pa-
tients reported some mild hypersensitivity as their sensation returned,
which was self-limited.
3. Discussion
The use of cold to lessen pain is one of the oldest forms of analgesia,
dating back as far as Hippocrates (460–377 BC), who described the use
of ice and snow packs for relieving surgical pain [10]. Today, the term
“cryoanalgesia” refers to the localized freezing of peripheral nerves.
Treatment occurs through application of a “cryoprobe,” which achieves
freezing temperature by the Joule–Thomson effect of rapidly expanding
gases that are contained within the chambers of the probe and
cryomachine. Common gases for medical use are carbon dioxide or ni-
trous oxide. When the nerve axon is frozen, the transmission of electri-
cal signal along the axon is prevented, providing analgesia. Thereafter,
Wallerian degeneration of axons occurs, starting at the point of injury
and moving toward the nerve endings. The fibrous neural structures in-
cluding the perineurium and epineurium, remain intact, facilitating ax-
onal regeneration. In addition, intercostal vessels remain intact owing to
the flowing blood acting as a heat sink [10–13]. The rate of this axonal
regeneration is approximately 1–3 mm/day. Animal cryoanalgesia stud-
ies have demonstrated that repair and regeneration of the axon and my-
elin sheath following cryoanalgesia is complete by approximately
4–6 weeks [11,14].
Cryoanalgesia has been used in adult patients since the 1970s, both
for acute and chronic pain control following thoracotomy, as well as
for treatment of postherpetic neuralgia [7,11,15–25]. We have now
adopted this technique for thoracoscopic application during the Nuss
procedure. As we gained more experience with the cryoanalgesia appli-
cation, we developed modifications that were unique to the technique
and its procedure-specific application.
First, we adapted our freezing technique based on patient size and
habitus. Our preference in all Nuss procedures is to elevate the sternum
and bluntly dissect the retrosternal space before introducing the Nuss
bar. We found that introducing the cryoanalgesia probe and thoracoscope
on the contralateral side after dissection and reaching across the
retrosternal space gives an excellent view of the intercostal nerves
and allows the surgeon to apply the probe directly perpendicular to
the nerves. However, the Atricure cryoprobe has a maximum probe
length of 27.5 cm, and is not long enough to reach the contralateral
chest wall in larger patients. Therefore, in these larger patients, we
gently curve the cryoprobe and apply it on the ipsilateral side, through
the skin incision created for the Nuss bar. The scope is either passed
from the contralateral chest across the anterior mediastinum or
through an ipsilateral port site. A longer probe is expected to become
available in 2017.
Next, we adopted single lung ventilation to improve visualization
during probe application. When we used single lumen endotracheal
tubes, we applied carbon dioxide insufflation at 5 mmHg pressure to fa-
cilitate the view of the posterolateral chest wall during cryoprobe appli-
cation, and patients were ventilated at smaller tidal volumes so that
lung would not obstruct the posterolateral chest wall view. However,
the use of double lumen endotracheal tubes allowed for selective lung
isolation during cryoprobe application. This modification dramatically
improved visualization of the chest wall and was more effective than
the use of carbon dioxide insufflation to suppress the lung volume.
The greatest advantage of cryoanalgesia over other methods of pain
control following the Nuss procedure is its long period of efficacy. Unlike
injectable regional blocks, which typically last less than 24 h [26], the
cryoanalgesia effect lasted at least 2 months in all 10 of our patients,
providing pain coverage throughout the entire postoperative period.
Moreover, the return of sensation is gradual, as opposed to short-
acting blocks or epidurals, which can cause a difficult transition period
after they wear off or are removed, and often leave patients struggling
to “catch up” with oral or intravenous narcotics [4].
One of the concerns about the use of cryoanalgesia is neuralgia,
which may occur during the axonal regeneration phase. Generally, our
patients experienced a natural transition from numbness to normal sen-
sation. One of our patients did develop a stinging pain consistent with
neuralgia 1 month after surgery, but this was transitory. Two additional
patients had some mild hypersensitivity along the anterior chest, which
was also self-limited. The exact cause of neuralgia postcryoanalgesia is
not known. Our conjecture is that there is incomplete cold thermal inju-
ry to the axon, which causes some portions of axon to be incompletely
inactivated. This creates a situation where axonal regeneration occurs
within a field of partially disrupted axons causing electrical signal er-
rors. We recommend exact application of the cryoprobe to the intercos-
tal nerves to achieve complete cryoablation.
4. Conclusion
In patients undergoing the Nuss procedure for pectus excavatum, in-
traoperative cryoanalgesia is easily performed under direct thoracoscopic
visualization. In our first 10 cryoanalgesia patients, pain was well con-
trolled, and the LOS was significantly shorter than for a previous cohort
of patients treated with thoracic epidurals. There appear to be no
long-term negative effects from cryoanalgesia, though we are continu-
ing to monitor two patients with prolonged numbness and further
long-term outcome studies are needed. Cryoanalgesia may be the
ideal pain management strategy for Nuss patients, because it is effec-
tive, long lasting, and has minimal risk.
Funding
This research did not receive any specific grant from funding agen-
cies in the public, commercial, or not-for-profit sectors.
Author contribution
Study conception and design: Sunghoon Kim.
Data acquisition: Olajire Idowu.
Analysis and data interpretation: Benjamin Padilla.
Drafting of the manuscript: Claire Graves.
Critical revision: Sang Lee.
Appendix A. Discussions
Claire E. Graves, MD.
 C. Graves et al. / Journal of Pediatric Surgery 52 (2017) 920–924
DR. CLAIRE GRAVES: Thank you for the opportunity to present. We
have no disclosures. The Nuss procedure is associated with
significant postoperative pain and there's no standardized ap-
proach to pain control. Most centers use epidural, drops of
epidural, and/or PCA, but epidural comes with significant
risks and without epidural, patients use high doses of nar-
cotics in a postop period.
Cryoanalgesia is a long-term, local and nerve blockage
achieved by direct freezing of the nerve. In our study, it was
directly applied to the intercostal nerve under thoracoscoptic
visualization. The freezing causes mullerian degeneration of
the acnon causing analgesia, but leaves the perineum and
upinerium intact which allows for the regrowth of the acnons
within their sheath.
The report, a retrospective review, of our early adoption peri-
od with the technique. We looked at the medical records of
the first ten patients who received cryoanalgesia during the
Nuss procedure. All had direct thoracoscopic application of
the cryo. Four to five nerves were treated on each side with
a negative 60-degree Celsius probe for 2 min at the level of
the incision, two rib spaces above and two spaces below. No
epidurals were used, only IV morphine or oral narcotics need-
ed and verbal pain scores were collected in the postop period.
Patient information is summarized here. Mean age was
16.8 years and mean Holler index was 4.4. The mean postop-
erative length of stay was 2 days, ranging from 1 to 3 days.
Compared to the 15 previous Nuss applications at our institu-
tion who were treated thoracic epidurals, mean length of stay
of significantly shorter with cryoanalgesia: 2 days compared
to 6.3 days and this was specifically significant.
Pain was well controlled in the postop period. Average pain
score on postop day 1 was 3.4. That went down to 3.2 on
postop day 2. There were only 2 patients remaining on postop
day 3 and they're scores are a little higher, as would be ex-
pected from patients who stayed a little longer. By one
postop, pain was very well controlled in all patients.
The average follow up was 8 months. We had 1 adverse event
in a 23-year-old female with bilateral plural efusion postop
which required percutaneous drainage. This same patient
also complained of some hypersensitivity and stinging
1 month postop which resolved with oral Gabapentin.
Eight of the ten patients had complete return of normal sensa-
tion by 2 to 4 months postoperatively. Two patients had some
persistent numbness at 8 and 9 months over the central ster-
num and overall, 2 patients had some mild hypersensitivity
as the sensation returned, including the one previously
discussed.
We learned some lessons in this early adoption period that
we'd like to share. First, we needed to adapt probe application
based on patient habitus. Our preference is to insert the probe
and scope through the contralateral chest wall, but the probe
is a little short for this to work in all patients. So, for larger pa-
tients, we had to insert the probe through the ipsilateral
chest. I'll have images describing this in just a second.
The second lesson is that single lung ventilation was ex-
tremely helpful for visualization of the posttrilateral chest
wall. And we've started to routinely place double - - and ET
tubes in our patients.
So, here is our preferred method when we elevate the ster-
num with a - - technique, divect out the retrosternal face
and pass both the probe and a 30-degree scope across the
chest. This is an external view and this is what you see what
the scope. Here's our adaptation for larger patients. The
probe is passed through the incision already made for the
Nuss bar and we look through a more inferior port site.
923
Here's a quick video of what that looks like through scope, if
that will play. There we go. This is our most superior - -
under the third rib. There's a pre-set 2-min pre-cycle followed
by an automatic active thaw cycle. And you can see that the
probe follows right - -. After the thaw, we simply marched
down to the next rib.
So, in conclusion, cryoanalgesia may be the optimal pain con-
trol strategy in the Nuss procedure. It's easily integrated into
the procedure and we've described some simple modifica-
tions for larger body habitus and to improve visualization. It
effectively controls pain at least 2 months if the chest wall re-
models. And we've seen significantly shorter hospital stays so
these kids can get back to school faster. Thank you.
MALE VOICE: open for discussion.
MALE VOICE: from Toronto. This sounds fantastic because, you
know, pain management is the biggest problem with these
Nuss - -. But I don't understand why just doing one side
would–are you going through both sides?
DR. GRAVES: Both sides, correct, I'm sorry if that wasn't clear in the
presentation.
MALE VOICE: Okay, and the other question is do you know what
this does to the intercostal vessels because they're sitting
right beside the nerve?
DR. GRAVES: Thank you for your question. The vessels serve as a
heat sink so the amount of blood that's following through
the vessels to seminate that freezing and the vessels are not
affected and that's been shown in animal studies going back
to the 1970s.
MALE VOICE: from Houston. It usually takes about 24 h for the
cryoanalgesia to really work. Have you found that you had
to bridge the patients in that first day of acute pain? Has
that actually been less than when you guys were doing non-
cryoanalgesia?
DR. GRAVES: Thank you for your question. So, we didn't look at that
specifically in this retrospective study, but we are currently
doing a prospective study where we're actively tracking
pain immediately postoperatively and through the hospital
stay. We have seen those patients wake up from surgery,
sometimes there is some acute pain there and they required
some extra fentanyl boluses in the PACU, for example.
MALE VOICE: from - -. Nice talk. Have you guys tried passing the
probe subcutaneously or below the muscles so you can actu-
ally get to the nerves from the outside? That's the way we do
it at UC-Davis, passing it actually under the muscles, but doing
a probe from the outside of the chest so you don't have to
cross the mediastinum.
DR. GRAVES: We have not done it that way and I've seen Dr. - - pre-
viously. We prefer to enter the thoracic application, just a
preference.
MALE VOICE: Okay, thank you.
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