Effect of Cryoanalgesia on Post-Thoracotomy Pain

Abstract

We prepared this study to determine the effect of cryoanalgesia on post-thoracotomy pain. In this double-blinded randomized clinical trial, 60 patients who underwent thoracotomy were divided into two groups (control and cryoanalgesia). Visual Analogue Scale (VAS, 0-10) was used for the measurement of severity of post-thoracotomy pain. It was classified into three categories: 0-1 (mild), 2-3 (moderate), and 4-10 (severe). Pethidine (0.5-1 mg/kg) was administered in case of need for both groups. Patients were visited at the hospital a week later, and were contacted by phone at the first, second, and third months post-operatively. Intensity of pain in the control group was higher than the cryoanalgesia group in all visits the follow-up period. On the second day, the frequencies of severe pain (4-10) were 33.3% and 0 in the control and cryoanalgesia groups, respectively. The mild pain on the seventh day was 13.3% and 83.3% in the control and cryoanalgesia groups, respectively (P < 0.01). Pethidine consumption was 151.6 ± 27 mg in the control group and 87.5 ±48 mg in the cryoanalgesia group on the first day post-operation (P < 0.001). Cryoanalgesia is a useful technique with not serious side effects in order to alleviate post-thoracotomy pain and reduce the need for opiate consumption.

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ORIGINAL REPORT
Corresponding Author: Hossein Mohammadinasab
Research Center of Anesthesiology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Tel: +98 912 3615382, +98 912 1767087, Fax: +98 21 444056051, E-mail: mohammadinasab@alumnus.tums.ac.ir
Effect of Cryoanalgesia on Post-Thoracotomy Pain
Sirous Momenzadeh1, Hedayatollah Elyasi2, Naser Valaie3, Badiozaman Radpey4,
Azizollah Abbasi5, Fatemeh Nematollahi1, and Hossein Mohammadinasab2
1 Department of Anesthesiology & Pain, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Research Center of Anesthesiology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Anesthesiology, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Department of Thoracocic Surgery, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6 Department of Obstetrics & Gynecology, Mothers Hospital, Tehran, Iran
Received: 14 Dec. 2009; Received in revised form: 28 Jan. 2010; Accepted: 12 Mar. 2010
Abstract- We prepared this study to determine the effect of cryoanalgesia on post-thoracotomy pain. In this
double-blinded randomized clinical trial, 60 patients who underwent thoracotomy were divided into two
groups (control and cryoanalgesia). Visual Analogue Scale (VAS, 0-10) was used for the measurement of
severity of post-thoracotomy pain. It was classified into three categories: 0-1 (mild), 2-3 (moderate), and 4-10
(severe). Pethidine (0.5-1 mg/kg) was administered in case of need for both groups. Patients were visited at
the hospital a week later, and were contacted by phone at the first, second, and third months post-operatively.
Intensity of pain in the control group was higher than the cryoanalgesia group in all visits the follow-up
period. On the second day, the frequencies of severe pain (4-10) were 33.3% and 0 in the control and
cryoanalgesia groups, respectively. The mild pain on the seventh day was 13.3% and 83.3% in the control and
cryoanalgesia groups, respectively (P < 0.01). Pethidine consumption was 151.6 ± 27 mg in the control group
and 87.5 ±48 mg in the cryoanalgesia group on the first day post-operation (P < 0.001). Cryoanalgesia is a
useful technique with not serious side effects in order to alleviate post-thoracotomy pain and reduce the need
for opiate consumption.
© 2011 Tehran University of Medical Sciences. All rights reserved.
Acta Medica Iranica 2011; 49(4): 241-245.
Keywords: Cryoanalgesia; Pain; Thoracotomy
Introduction
In spite of recent progressive achievements in
anesthesiology, postoperative pain management and
treatment in patients is still one of the most complicated
problems among anesthesiologists. Thoracotomy is one
of the most painful surgical incisions currently used (1-
2). Inadequate control of post-thoracotomy pain is
associated with increased postoperative morbidity (3).
This association causes a significant relationship
between effective postoperative analgesia and the rate of
postoperative pulmonary complications such as
atelectasis, infections, etc after thoracotomies (4). The
true incidence of post-thoracotomy pain is difficult to
determine, with a reported range from 5% to 80% (5-8).
Chronic post-thoracotomy pain consists of different
types of pain, both myofascial and neuropathic pain
(6,9).
Along with persistent characteristic, post-
thoracotomy pain has cardiopulmonary complications as
well as psychological adverse effects. Based on previous
studies, pain relief in patients undergoing thoracotomy
operation is a debatable issue among anesthesiologists
(10-11). There are different methods of pain
management in these patients (1,12). It has been
reported that the local analgesia is one of the most
efficient ways of pain relief (13). Of these, the
cryoanalgesia is a local pain controlling method that is
progressively applied because of the ease of handling,
low cost and accessibility. Cryoanalgesia (the use of
cold to provide anesthesia or analgesia) is an old
analgesic method but still is in current clinical use (14).
Its intraoperative use in providing postoperative
analgesia for acute thoracic pain problems via an open
thoracotomy is well described (15). However, there are
controversies about the use of this method in post-

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Effect of cryoanalgesia on post-thoracotomy pain
242 Acta Medica Iranica, Vol. 49, No. 4 (2011)
thoracotomy pain (13,16). As a result, we decided to
determine the effect of cryoanalgesia on post-
thoracotomy pain.
Materials and Methods
This double blind randomized clinical trial included 60
patients with the age range of 19-51 years and ASA
(American Society of Anesthesiologists) classes I-III for
whom thoracotomy via posterolateral incisions were
required. The exclusion criteria were consisted of:
opioids or any other illegal drug addicts and diabetics
who were suffering from the disease for more than 10
years. Midazolam (2 mg/kg BW) and fentanyl (3 mg/kg
BW) were administered, as pre-medications for patients
in the operation room. The monitoring was performed
by pulse oximeter, ECG (Electrocardiography), end tidal
carbon dioxide (CO2), arterial blood gas analysis (ABG),
and invasive blood pressure. The patients were
preoxygenated using 100% oxygen for three minutes.
Anesthesia was induced by thiopental (5 mg/kg BW)
and atracurium (0.5 mg/kg BW) with a bolus dose which
continued in 20-minute intervals. Three minutes later,
intubation was done and then thoracotomy by postero-
lateral incision was performed. The techniques of
thoracotomy and suture materials were the same in all
patients.
Before the operation, the patients were randomly
divided by simple randomization by random table into
two groups: control and cryoanalgesia. In cryoanalgesia
group, before closure of the thorax, the intercostal
nerves (one at the level of the incision, one cranial, and
one caudal) were identified and exposed to peeling off
the parietal pleura. The Kooland cryoanalgesiaprobe
(administering CO2 as the cooling agent, JP- 1, Kooland,
China) was placed on each nerve, under direct vision.
Each nerve received a 90-second application of cold (-
70o C). Patients received halothane 1 minimum alveolar
concentration (MAC), oxygen and nitrous oxide (N2O),
50% of each, and atracurium (0.2 mg/kg) as
maintenance drugs. Anesthesia was maintained with
fentanyl (2 µg/kg; every half an hour) during the
operation. Neuromuscular blockade was reversed by
atropine (1.25 mg) and neostigmine (2.5 mg). Pethidine
(0.5-1 mg/kg) was administered by a nurse in the case of
need in both the control and cryoanalgesia groups.
A visual analogue scale (VAS, on a scale of 0-10)
was used in order to measure pain after thoracotomy.
The VAS was classified into three groups as follows: 0-
1 (no pain to mild), 2-3 (moderate), 4-10 (severe) (18).
The VAS recording was done at different postoperative
times: 0 (start of the recovery period), 0-24 hr (every
two hours), 24-48 hr (every four hours) and the third to
7th day (every morning and evening) following surgery
by a trained nurse. Both the nurse and the patients were
unaware of patient group assignments.
Patients were visited at the hospital one week after
discharge and were contacted by telephone at the first,
second, and third month post-operatively. Information
about the side effects including dysesthesia, allodynia
and hypoesthesia were recorded as well.
Descriptive indices including frequency, percentage,
mean ± SD were used to express data. The Chi-Square
or Fischer’s exact tests were used to compare qualitative
variables between the control and cryoanalgesia groups.
All analyses were performed using SPSS software
for Windows (Ver. 13.0) (SPSS Inc., Chicago, IL).
Results
Sixty patients were randomized into two equal groups
(n=30 each of them). There was no significant difference
between the two groups in terms of age, ASA class, and
the operation site (Table 1). As shown in Table 1, the
male population in the cryoanalgesia group (83.3%) was
significantly higher than the control group (50%), P <
0.01.
Table 1. Comparison of basic characteristics between the two studied groups
Control (N = 30) Cryoanalgesia (N = 30) P value
Age, mean ± SD 41.3 ± 15 41.9 ± 16 NS
Gender
Male
Female
15 (50.0%)
15 (50.0%)
25 (83.3%)
5 (16.7%)
<0.01
Weight, mean ± SD 64.7 ±10.6 64.1 ± 12.1 NS
Site of thoracotomy
Right
Left
22 (73.3%)
8 (26.7%)
19 (63.3%)
11 (36.7%)
NS
ASA class
I
II
III
4 (13.3%)
25 (83.4%)
1 (3.3%)
3 (10.0%)
27 (90.0%)
0
NS
Abbreviations: SD = standard deviation; NS = not significant; ASA = American Society of Anesthesiologists

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S. Momenzadeh, et al.
Acta Medica Iranica, Vol. 49, No. 4 (2011) 243
0
1
2
3
4
5
6
7
8
9
10
first day
second day
third day
fourth day
fifth day
sixth day
seventh day
fallow up days
pain score
Control
Cryoanalgesia
Figure 1. Mean score of patient pain in both groups during the follow-up period
Postoperative pain scores, in both control and
cryoanalgesia groups, are presented in Figure 1. As
depicted, the intensity of pain in the control group was
higher than the cryoanalgesia group throughout the
follow-up period. On the second day after the operation,
the frequencies of severe pain score were 33.3% and 0 in
the control and cryoanalgesia groups, respectively.
Subsequently, the "no to mild pain" category on the
seventh day was observed in 13.3% and 83.3% of the
control and cryoanalgesia groups, respectively. In
general, the pain intensity was significantly higher in the
control group compared to the cryoanalgesia group (P<
0.001). Table 2 presents the severity of pain according to
VAS categories between the two studied groups from
days one to six.
Mean amount of pethidine administration during the
study period is presented in Figure 2. Mean ± SD
administration of pethidine was significantly higher in
the control group than the cryoanalgesia patients on day
one post-operatively (151.6 ± 27 mg vs. 87 ± 48 mg; P <
0.001). The usage of pethidine in the cryoanalgesia
group was ended on the forth day after operation;
however the control group subjects required pethidine
until the seventh day post-operatively.
The percentage of sensory dysfunction in the patients
who underwent cryoanalgesia surgery showed that the
hypoesthesia occurrence was in the following pattern:
90% at the end of the first postoperative week, 76.7% at
the end of the first month, and 16.6% at the end of the
second month. No hypoesthesia was recorded at the end
of the third month. In addition, both allodynia and
dysesthesia were diminished to 10% at the end of the
first month and no further one was observed at the end
of the second month.
0
20
40
60
80
100
120
140
160
first day
second day
third day
fourth day
fifth day
sixth day
seven day
fallow up days
Pethidine (mg)
Control
Cryoanalgesia
Figure 2. Mean of patient consumption (mg) in both groups during the follow-up period

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Effect of cryoanalgesia on post-thoracotomy pain
244 Acta Medica Iranica, Vol. 49, No. 4 (2011)
Discussion
This is the first study, as to our knowledge, to evaluate
the clinical efficacy of cryoanalgesia in controlling the
post-operative pain of a group of Iranian patients who
underwent thoracotomy. The present results demonstrate
that the severity of thoracotomy-induced pain was better
controlled using cryoanalgesia method. This finding is
in affirmity with previous reports about the application
of cryoanalgesia in thoracotomy patients. In Maiwand et
al. study (18) the successful effect of cryoanalgesia on
pain management after thoracotomy has been reported.
They also noted that the consumption of opiates was
diminished after using cryoanalgesia. It has been shown
that efficacy of cryoanalgesia on postoperative pain
relief as well as improvement in pulmonary function in
patients underwent the cryoanalgesia was more
prominent in comparison to intravenous opiates received
patients (19, 17). There are some controversial
evidences on effectiveness of cryoanalgesia; in other
words, in some previous investigations (20), the
analgesic efficacy of cryoanalgesia has been reported
with less effect on pain relief and long-term
postoperative side effects. These controversies might be
because of lack of appropriate cryoanalgesia probe and
insufficient nerve freezing, nerve freezing at a point
distal to the branches, long freezing time, and nerve
freezing with a blind technique and with an unsuitable
nerve locator. Although the mechanism of cryoanalgesia
in pain relief is still unknown, it is likely that when
cryoanalgesia probe contacts with peripheral nerves, it
causes a second-grade nerve lesion (Axonotmesis). The
effects of cryoanalgesia are directly related to the
formation of intra- and extracellular ice crystals, which
result in microvascular changes and alteration of cellular
osmolality and permeability, causing cell damage and
disruption of nerve conduction, and consequently cause
analgesia.
The obtained results about the need for pethidine
administration are in agreement with data reported by
Orr et al. (19) and Pastor et al. (17) which showed that
the opiate (pethidine) consumption in the control group
was higher than the patients with cryoanalgesia surgery.
It is likely concerning the disruption of the axonal
function and conduction, the pain perception and
sensation is being reduced in the patients; therefore,
fewer opiates will be demanded. Another considerable
finding of the present study is the significant decrease in
the incidence of dysesthesia, hypoesthesia and allodynia
during the follow-up period in patients who received
cyoanalgesia. Hypoesthesia was gradually disappeared
at the end of the third month as well as dysesthesia and
allodynia which were significantly reduced at the end of
the second month. In case of allodynia and dysesthesia it
could be questioned whether these abnormalities are
related to surgery-induced trauma or to the
cryoanalgesiagenic outcomes? One of the limitations in
the current investigation was that the incidence rate of
these abnormalities was not measured in the control
group. In previous studies, all kinds of abovementioned
side effects have been observed in the thoracotomy
patients without cryoanalgesia. So, we suggest that
comparative analyses of postoperative side effects in
cryoanalgesia-group versus non-cryoanalgesia-group
should not be underestimated in the future hypotheses. It
is suggested that comparative interaction of pain relief
due to narcotic analgesia and cryoanalgesia should be
considered in the upcoming studies. The current findings
propose that the effect of cryoanalgesia on the pain
alleviation of other kinds of surgical operations
collaborating with the moderate to sever neuropathic
pain should be explored.
In conclusion, cryoanalgesia is an advantageous
technique in order to relieve post-thoracotomy pain and
reduce the opiate consumption. Additionally,
cryoanalgesia-induced sensory abnormalities
disappeared during the time. In the current research, the
cryoanalgesia is recommended to thoracic surgeons and
anesthesiologists in order to relieve post-thoracotomy
pain.
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