Accepted Manuscript Effects of Peritoneal Ropivacaine Nebulization for Pain Control After Laparoscopic Gynecologic Surgery Marta Somaini, MD Pietro Brambillasca, MD Pablo M. Ingelmo, MD Federica Lovisari, MD Stefano Scalia Catenacci, MD Valeria Rossini, MD Mario Bucciero, MD Emre Sahillioglu, MD Alessandro Buda, MD Mauro Signorelli, MD Mauro Gili, MD Girish P. Joshi, FFARCSI Roberto Fumagalli, MD Catherine E. Ferland, PhD Pierre Diemunsch, PhD PII:
S1553-4650(14)00239-8
DOI:
10.1016/j.jmig.2014.03.021
Reference:
JMIG 2287
To appear in:
The Journal of Minimally Invasive Gynecology
Received Date: 24 February 2014 Revised Date:
24 March 2014
Accepted Date: 25 March 2014
Please cite this article as: Somaini M, Brambillasca P, Ingelmo PM, Lovisari F, Catenacci SS, Rossini V, Bucciero M, Sahillioglu E, Buda A, Signorelli M, Gili M, Joshi GP, Fumagalli R, Ferland CE, Diemunsch P, Effects of Peritoneal Ropivacaine Nebulization for Pain Control After Laparoscopic Gynecologic Surgery, The Journal of Minimally Invasive Gynecology (2014), doi: 10.1016/j.jmig.2014.03.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Somaini 1 1
Effects of Peritoneal Ropivacaine Nebulization for Pain Control After
2
Laparoscopic Gynecologic Surgery
3 Marta SOMAINI1 MD, Pietro BRAMBILLASCA2 MD, Pablo M. INGELMO3 MD, Federica
5
LOVISARI4 MD, Stefano Scalia CATENACCI4 MD, Valeria ROSSINI5 MD, Mario
6
BUCCIERO6 MD, Emre SAHILLIOGLU7 MD, Alessandro BUDA8 MD, Mauro SIGNORELLI8
7
MD, Mauro GILI4 MD, Girish P. JOSHI9 FFARCSI, Roberto FUMAGALLI1,5 MD, Catherine E.
8
FERLAND3 PhD, Pierre DIEMUNSCH10 PhD.
SC
9
RI PT
4
10 11
1. U.O. Anestesia e Rianimazione 1 Ospedale Niguarda Ca' Granda
12
2. U.O. Anestesia e Rianimazione I, Ospedale Riuniti di Bergamo, Italy.
13
3. McGill University Health Centre, Montreal Children’s Hospital. Montreal, Canada.
14
4. U.O. Anestesia e Rianimazione. Ospedale San Gerardo di Monza. Italy.
15
5. Università degli studi Milano Bicocca. Italy.
16
6. Service d'Anesthésie Réanimation. Hôpital Lariboisière. Paris, France.
17
7. Department of Anesthesia and Intensive Care, Kozyatağı Acıbadem Hospital, İstanbul, Turkey.
18
8. U.O. Ginecologia e Ostetricia. Ospedale San Gerardo Monza, Italy.
19
9. Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical
20
Center, Dallas, Texas. USA.
21
10. Service d’Anesthésiologie–Réanimation Chirurgicale, CHU de Hautepierre, and EA 3072, Faculté de
22
Médecine, Strasbourg, France.
M AN U
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23 24 25
Milan, Italy.
26
Corresponding Author:
27
Pablo M. Ingelmo
28
Department of Anesthesia. Montreal Children’s Hospital.
29
2300 Tupper Street, Room C-1115. Montreal (Quebec), Canada H3H 1P3
30
Phone: +1-514-412-4400 Ext 23486 FAX: +1-514-412-4341
31
Email: [email protected]
32
ACCEPTED MANUSCRIPT Somaini 2 33
Precis: Peritoneal administration of ropivacaine produced superior pain relief than placebo after
34
gynecologic laparoscopy. Ropivacaine nebulization reduced morphine consumption and time to
35
unassisted walking after surgery.
RI PT
36 37
Key words: acute pain, regional techniques; anesthetic techniques, insufflation; anesthetic
38
techniques, regional; analgesics, postoperative; local anesthetics, ropivacaine
SC
39 40
M AN U
41 42 43 Declaration of interests
45
None of the authors declared a conflict of interest.
TE D
44
46 Funding
48
This work was supported by the Department of Experimental Medicine Milan Bicocca
49
University and the Service d’Anesthésiologie – Réanimation Chirurgicale, EA 3072, CHU de
50
Hautepierre 67000 Strasbourg, France
AC C
51
EP
47
52
Data were presented as a poster presentation at Euroanaesthesia 2010 (European Society of
53
Anaesthesiology congress); June 12−15 2010; Helsinki, Finland.
54
ACCEPTED MANUSCRIPT Somaini 3 Abstract
56
Study Objective: This trial evaluated the effects of peritoneal cold nebulization of ropivacaine on
57
pain control after gynecologic laparoscopy.
58
Design: Evidence obtained from a properly designed, randomized, double-blind, placebo-
59
controlled trial (Canadian Task Force classification I).
60
Setting: San Gerardo Hospital of Monza, Italy, a tertiary care center.
61
Patients: One hundred and thirty five adult women, ASA I-III, scheduled for operative
62
laparoscopy.
63
Intervention: patients were randomized to receive either nebulization of ropivacaine 30 mg
64
before surgery (PREOPERATIVE); nebulization of ropivacaine 30 mg after surgery
65
(POSTOPERATIVE); instillation of ropivacaine 100 mg before surgery (INSTILLATION) or
66
saline (CONTROL). Nebulization was performed using the Aeroneb Pro device (Aerogen,
67
Galway, Ireland).
68
Measurement and Main Results: Pain scores, morphine consumption, and ambulation time were
69
collected in post anesthesia care unit and at 4, 6 and 24 hours, postoperatively. 118 patients
70
completed the study. Patients in the PREOPERATIVE group referred lower pain Numeric
71
Ranking Scale values compared with those in the CONTROL group (net difference 2 points,
72
95%CI 0.3 to 3.1 at 4 hours, 1 to 3 at 6 hours; and 0.7 to 3 at 24 hours, p=0.01) Patients in the
73
PREOPERATIVE group consumed significantly less morphine than those in the CONTROL
74
group (net difference 7 mg, 95%CI 0.7 to 13, p=0.02). Greater number of patients receiving
75
nebulization walked without assistance within 12 hours after awakening than those in the
76
INSTILLATION and CONTROL groups (net difference 15%, 95%CI 6 to 24%, p=0.001).
AC C
EP
TE D
M AN U
SC
RI PT
55
ACCEPTED MANUSCRIPT Somaini 4 77
Conclusions: Cold nebulization of ropivacaine before surgery reduced postoperative pain,
78
morphine consumption, and was associated with earlier walking without assistance.
AC C
EP
TE D
M AN U
SC
RI PT
79
ACCEPTED MANUSCRIPT Somaini 5 Introduction
81
Visceral pain after laparoscopic procedures can be as intense as the incisional pain. Its
82
pathophysiology is multifactorial including inflammation and injury associated to the insufflated
83
gas and manipulation of abdominal structures.1-2 The effectiveness of peritoneal instillation of
84
long-acting local anesthetics has been controverted. The place of local anesthetic instillation, the
85
timing of administration, the differences in local anesthetic doses, and the non-homogenous
86
delivery of analgesic solutions within the abdominal cavity may all contribute to inconsistent
87
results.3-6
88
Intraperitoneal nebulization of local anesthetic allows a uniform dispersion of the solution
89
throughout the peritoneum and combines the analgesic benefits of gas conditioning and local
90
anesthetic instillation.7 Microvibration-based aerosol humidification devices (i.e. cold
91
nebulization) deliver significant amounts of local anesthetics in the abdominal cavity.8
92
Several studies have reported that cold nebulization of local anesthetics in the abdominal cavity
93
significantly reduced the intensity of pain, the opioid consumption and time to unassisted
94
walking after laparoscopic cholecystectomy.7
95
find a significant advantage on pain control in patients undergoing gynecologic laparoscopic
96
procedures. Thus, controversy exists regarding the benefits of local anesthetic nebulization for
97
pain control after gynecologic laparoscopic surgery.
98
In an attempt to fully understand the potential use of peritoneal cold nebulization of ropivacaine,
99
we designed a double-blind randomized controlled trial to evaluate its effects on the
100
postoperative pain control after gynecologic laparoscopic surgery. We hypothesized that cold
101
nebulization of ropivacaine would provide better pain relief than ropivacaine instillation or
102
nebulization of saline.
TE D
M AN U
SC
RI PT
80
However, Kaufman and colleagues11 did not
AC C
EP
9 10
ACCEPTED MANUSCRIPT Somaini 6 Methods
104
This single-centre, randomized, double blind, placebo-controlled study was approved by the San
105
Gerardo Hospital ethical committee (Ref 272, N° 1732 of 24/04/2008), an academic institution in
106
Northern Italy, and it was registered www.clinicaltrial.gov on 2012/01/18 with the number
107
NCT01512914.
108
All patients provided written informed consent. Eligible participants were adult women (> 18
109
years of age), American Society of Anesthesiologist (ASA) physical status I-III scheduled for
110
elective gynecologic laparoscopic surgery. Patients were excluded if they received non-steroidal
111
anti-inflammatory drugs and/or opioids during the previous two weeks or chronic pain treatment
112
(including any analgesic therapy for more than four weeks in the last six months), and
113
antiepileptic therapy. Patients with history of alcohol or drug addiction, severe hepatic or renal
114
impairment, acute abdominal infectious disease or inflammatory chronic disease, allergy to the
115
study drugs, cognitive impairment or were pregnant or lactating were also excluded. Eligibility
116
criteria and written informed consent were collected during the preoperative anesthesia
117
evaluation and confirmed on the day of surgery by a research assistant.
118
A standardized surgical technique including placement of a 12-mm port via a subumbilical
119
incision, as well as placement of three to four 5-mm ports in the epigastric area and on both sides
120
of the lower abdomen were performed in all cases. Pneumoperitoneum was achieved using non-
121
humidified, non-heated carbon dioxide (CO2) at a pressure of 12 to 14 mmHg. A standardized
122
general anesthetic technique was used for all subjects. Patients received oral diazepam 5-7 mg as
123
premedication. Induction was performed with propofol 3-4 mg kg-1 IV and tracheal intubation
124
was facilitated with cisatracurium 0.15 mg kg-1 IV. Anesthesia was maintained with sevoflurane
125
1.5-2.5% end-tidal concentration titrated to maintain state entropy values between 45 and 60
AC C
EP
TE D
M AN U
SC
RI PT
103
ACCEPTED MANUSCRIPT Somaini 7 (Entropy sensor™, M-Entropy™ module, GE Healthcare). Fentanyl 1-2 mcg kg-1 was
127
administered to maintain mean arterial blood pressure and heart rate within ± 20 % of baseline
128
values. Cisatracurium 0.03 mg kg-1 was administered to maintain a train of four counts (TOF)
129
response of 1-2, as well as according to clinical needs. Ventilation was controlled to maintain
130
end-tidal CO2 values between 35 and 40 mmHg. Operating room temperature was set at 20°C
131
and patients were kept warm using forced warm-air device and warmed intravenous solutions. At
132
the end of surgery, residual muscle paralysis was reversed, and tracheal extubation was
133
performed once clinical, and TOF criteria were achieved.
134
Prophylaxis for postoperative nausea and vomiting (PONV) included dexamethasone 4 mg and
135
ondansetron 4 mg. Prevention of postoperative pain included paracetamol 15 mg kg-1 IV during
136
surgery and then every 6 h for 48 hours, and infiltration of each abdominal incision with 3 ml of
137
ropivacaine 0.3%, just prior to wound closure. Upon arrival in the post anesthesia care unit
138
(PACU) patients received morphine 3 mg IV boluses to achieve a dynamic pain Numeric
139
Ranking Scale (NRS) score ≤ 3, followed by intravenous patient-controlled analgesia (IV-PCA)
140
with morphine 1 mg bolus, lockout time of 5 minutes. Patients were encouraged to ambulate as
141
soon as possible.
142
Patients received one of the following treatments: instillation of saline 20 ml and nebulization of
143
ropivacaine 1% 3 ml (30 mg) before surgery, and nebulization of saline 3 ml after surgery
144
(PREOPERATIVE nebulization group); instillation of saline 20 ml and nebulization of saline 3
145
ml before surgery, and nebulization of ropivacaine 1% 3 ml (30 mg) after surgery
146
(POSTOPERATIVE nebulization group); instillation of ropivacaine 0.5% 20 ml (100 mg) and
147
nebulization of saline 3 ml before surgery, and nebulization of saline 3 ml after surgery
AC C
EP
TE D
M AN U
SC
RI PT
126
ACCEPTED MANUSCRIPT Somaini 8 (INSTILLATION group); instillation of saline 20 ml before surgery, and nebulization of saline 3
149
ml before and after surgery (CONTROL group).
150
Ropivacaine and saline were nebulized using the Aeroneb Pro® system (Aerogen, Galway,
151
Ireland) through a 12-mm port inserted via the umbilical wound. The Aeroneb Pro® device is a
152
high frequency vibrating membrane nebulizer, allowing simultaneous humidification and
153
delivery of local anesthetic, providing cold nebulization by microvibration with more than 80%
154
fine particles with a diameter
S1553-4650(14)00239-8
DOI:
10.1016/j.jmig.2014.03.021
Reference:
JMIG 2287
To appear in:
The Journal of Minimally Invasive Gynecology
Received Date: 24 February 2014 Revised Date:
24 March 2014
Accepted Date: 25 March 2014
Please cite this article as: Somaini M, Brambillasca P, Ingelmo PM, Lovisari F, Catenacci SS, Rossini V, Bucciero M, Sahillioglu E, Buda A, Signorelli M, Gili M, Joshi GP, Fumagalli R, Ferland CE, Diemunsch P, Effects of Peritoneal Ropivacaine Nebulization for Pain Control After Laparoscopic Gynecologic Surgery, The Journal of Minimally Invasive Gynecology (2014), doi: 10.1016/j.jmig.2014.03.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Somaini 1 1
Effects of Peritoneal Ropivacaine Nebulization for Pain Control After
2
Laparoscopic Gynecologic Surgery
3 Marta SOMAINI1 MD, Pietro BRAMBILLASCA2 MD, Pablo M. INGELMO3 MD, Federica
5
LOVISARI4 MD, Stefano Scalia CATENACCI4 MD, Valeria ROSSINI5 MD, Mario
6
BUCCIERO6 MD, Emre SAHILLIOGLU7 MD, Alessandro BUDA8 MD, Mauro SIGNORELLI8
7
MD, Mauro GILI4 MD, Girish P. JOSHI9 FFARCSI, Roberto FUMAGALLI1,5 MD, Catherine E.
8
FERLAND3 PhD, Pierre DIEMUNSCH10 PhD.
SC
9
RI PT
4
10 11
1. U.O. Anestesia e Rianimazione 1 Ospedale Niguarda Ca' Granda
12
2. U.O. Anestesia e Rianimazione I, Ospedale Riuniti di Bergamo, Italy.
13
3. McGill University Health Centre, Montreal Children’s Hospital. Montreal, Canada.
14
4. U.O. Anestesia e Rianimazione. Ospedale San Gerardo di Monza. Italy.
15
5. Università degli studi Milano Bicocca. Italy.
16
6. Service d'Anesthésie Réanimation. Hôpital Lariboisière. Paris, France.
17
7. Department of Anesthesia and Intensive Care, Kozyatağı Acıbadem Hospital, İstanbul, Turkey.
18
8. U.O. Ginecologia e Ostetricia. Ospedale San Gerardo Monza, Italy.
19
9. Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical
20
Center, Dallas, Texas. USA.
21
10. Service d’Anesthésiologie–Réanimation Chirurgicale, CHU de Hautepierre, and EA 3072, Faculté de
22
Médecine, Strasbourg, France.
M AN U
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EP
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23 24 25
Milan, Italy.
26
Corresponding Author:
27
Pablo M. Ingelmo
28
Department of Anesthesia. Montreal Children’s Hospital.
29
2300 Tupper Street, Room C-1115. Montreal (Quebec), Canada H3H 1P3
30
Phone: +1-514-412-4400 Ext 23486 FAX: +1-514-412-4341
31
Email: [email protected]
32
ACCEPTED MANUSCRIPT Somaini 2 33
Precis: Peritoneal administration of ropivacaine produced superior pain relief than placebo after
34
gynecologic laparoscopy. Ropivacaine nebulization reduced morphine consumption and time to
35
unassisted walking after surgery.
RI PT
36 37
Key words: acute pain, regional techniques; anesthetic techniques, insufflation; anesthetic
38
techniques, regional; analgesics, postoperative; local anesthetics, ropivacaine
SC
39 40
M AN U
41 42 43 Declaration of interests
45
None of the authors declared a conflict of interest.
TE D
44
46 Funding
48
This work was supported by the Department of Experimental Medicine Milan Bicocca
49
University and the Service d’Anesthésiologie – Réanimation Chirurgicale, EA 3072, CHU de
50
Hautepierre 67000 Strasbourg, France
AC C
51
EP
47
52
Data were presented as a poster presentation at Euroanaesthesia 2010 (European Society of
53
Anaesthesiology congress); June 12−15 2010; Helsinki, Finland.
54
ACCEPTED MANUSCRIPT Somaini 3 Abstract
56
Study Objective: This trial evaluated the effects of peritoneal cold nebulization of ropivacaine on
57
pain control after gynecologic laparoscopy.
58
Design: Evidence obtained from a properly designed, randomized, double-blind, placebo-
59
controlled trial (Canadian Task Force classification I).
60
Setting: San Gerardo Hospital of Monza, Italy, a tertiary care center.
61
Patients: One hundred and thirty five adult women, ASA I-III, scheduled for operative
62
laparoscopy.
63
Intervention: patients were randomized to receive either nebulization of ropivacaine 30 mg
64
before surgery (PREOPERATIVE); nebulization of ropivacaine 30 mg after surgery
65
(POSTOPERATIVE); instillation of ropivacaine 100 mg before surgery (INSTILLATION) or
66
saline (CONTROL). Nebulization was performed using the Aeroneb Pro device (Aerogen,
67
Galway, Ireland).
68
Measurement and Main Results: Pain scores, morphine consumption, and ambulation time were
69
collected in post anesthesia care unit and at 4, 6 and 24 hours, postoperatively. 118 patients
70
completed the study. Patients in the PREOPERATIVE group referred lower pain Numeric
71
Ranking Scale values compared with those in the CONTROL group (net difference 2 points,
72
95%CI 0.3 to 3.1 at 4 hours, 1 to 3 at 6 hours; and 0.7 to 3 at 24 hours, p=0.01) Patients in the
73
PREOPERATIVE group consumed significantly less morphine than those in the CONTROL
74
group (net difference 7 mg, 95%CI 0.7 to 13, p=0.02). Greater number of patients receiving
75
nebulization walked without assistance within 12 hours after awakening than those in the
76
INSTILLATION and CONTROL groups (net difference 15%, 95%CI 6 to 24%, p=0.001).
AC C
EP
TE D
M AN U
SC
RI PT
55
ACCEPTED MANUSCRIPT Somaini 4 77
Conclusions: Cold nebulization of ropivacaine before surgery reduced postoperative pain,
78
morphine consumption, and was associated with earlier walking without assistance.
AC C
EP
TE D
M AN U
SC
RI PT
79
ACCEPTED MANUSCRIPT Somaini 5 Introduction
81
Visceral pain after laparoscopic procedures can be as intense as the incisional pain. Its
82
pathophysiology is multifactorial including inflammation and injury associated to the insufflated
83
gas and manipulation of abdominal structures.1-2 The effectiveness of peritoneal instillation of
84
long-acting local anesthetics has been controverted. The place of local anesthetic instillation, the
85
timing of administration, the differences in local anesthetic doses, and the non-homogenous
86
delivery of analgesic solutions within the abdominal cavity may all contribute to inconsistent
87
results.3-6
88
Intraperitoneal nebulization of local anesthetic allows a uniform dispersion of the solution
89
throughout the peritoneum and combines the analgesic benefits of gas conditioning and local
90
anesthetic instillation.7 Microvibration-based aerosol humidification devices (i.e. cold
91
nebulization) deliver significant amounts of local anesthetics in the abdominal cavity.8
92
Several studies have reported that cold nebulization of local anesthetics in the abdominal cavity
93
significantly reduced the intensity of pain, the opioid consumption and time to unassisted
94
walking after laparoscopic cholecystectomy.7
95
find a significant advantage on pain control in patients undergoing gynecologic laparoscopic
96
procedures. Thus, controversy exists regarding the benefits of local anesthetic nebulization for
97
pain control after gynecologic laparoscopic surgery.
98
In an attempt to fully understand the potential use of peritoneal cold nebulization of ropivacaine,
99
we designed a double-blind randomized controlled trial to evaluate its effects on the
100
postoperative pain control after gynecologic laparoscopic surgery. We hypothesized that cold
101
nebulization of ropivacaine would provide better pain relief than ropivacaine instillation or
102
nebulization of saline.
TE D
M AN U
SC
RI PT
80
However, Kaufman and colleagues11 did not
AC C
EP
9 10
ACCEPTED MANUSCRIPT Somaini 6 Methods
104
This single-centre, randomized, double blind, placebo-controlled study was approved by the San
105
Gerardo Hospital ethical committee (Ref 272, N° 1732 of 24/04/2008), an academic institution in
106
Northern Italy, and it was registered www.clinicaltrial.gov on 2012/01/18 with the number
107
NCT01512914.
108
All patients provided written informed consent. Eligible participants were adult women (> 18
109
years of age), American Society of Anesthesiologist (ASA) physical status I-III scheduled for
110
elective gynecologic laparoscopic surgery. Patients were excluded if they received non-steroidal
111
anti-inflammatory drugs and/or opioids during the previous two weeks or chronic pain treatment
112
(including any analgesic therapy for more than four weeks in the last six months), and
113
antiepileptic therapy. Patients with history of alcohol or drug addiction, severe hepatic or renal
114
impairment, acute abdominal infectious disease or inflammatory chronic disease, allergy to the
115
study drugs, cognitive impairment or were pregnant or lactating were also excluded. Eligibility
116
criteria and written informed consent were collected during the preoperative anesthesia
117
evaluation and confirmed on the day of surgery by a research assistant.
118
A standardized surgical technique including placement of a 12-mm port via a subumbilical
119
incision, as well as placement of three to four 5-mm ports in the epigastric area and on both sides
120
of the lower abdomen were performed in all cases. Pneumoperitoneum was achieved using non-
121
humidified, non-heated carbon dioxide (CO2) at a pressure of 12 to 14 mmHg. A standardized
122
general anesthetic technique was used for all subjects. Patients received oral diazepam 5-7 mg as
123
premedication. Induction was performed with propofol 3-4 mg kg-1 IV and tracheal intubation
124
was facilitated with cisatracurium 0.15 mg kg-1 IV. Anesthesia was maintained with sevoflurane
125
1.5-2.5% end-tidal concentration titrated to maintain state entropy values between 45 and 60
AC C
EP
TE D
M AN U
SC
RI PT
103
ACCEPTED MANUSCRIPT Somaini 7 (Entropy sensor™, M-Entropy™ module, GE Healthcare). Fentanyl 1-2 mcg kg-1 was
127
administered to maintain mean arterial blood pressure and heart rate within ± 20 % of baseline
128
values. Cisatracurium 0.03 mg kg-1 was administered to maintain a train of four counts (TOF)
129
response of 1-2, as well as according to clinical needs. Ventilation was controlled to maintain
130
end-tidal CO2 values between 35 and 40 mmHg. Operating room temperature was set at 20°C
131
and patients were kept warm using forced warm-air device and warmed intravenous solutions. At
132
the end of surgery, residual muscle paralysis was reversed, and tracheal extubation was
133
performed once clinical, and TOF criteria were achieved.
134
Prophylaxis for postoperative nausea and vomiting (PONV) included dexamethasone 4 mg and
135
ondansetron 4 mg. Prevention of postoperative pain included paracetamol 15 mg kg-1 IV during
136
surgery and then every 6 h for 48 hours, and infiltration of each abdominal incision with 3 ml of
137
ropivacaine 0.3%, just prior to wound closure. Upon arrival in the post anesthesia care unit
138
(PACU) patients received morphine 3 mg IV boluses to achieve a dynamic pain Numeric
139
Ranking Scale (NRS) score ≤ 3, followed by intravenous patient-controlled analgesia (IV-PCA)
140
with morphine 1 mg bolus, lockout time of 5 minutes. Patients were encouraged to ambulate as
141
soon as possible.
142
Patients received one of the following treatments: instillation of saline 20 ml and nebulization of
143
ropivacaine 1% 3 ml (30 mg) before surgery, and nebulization of saline 3 ml after surgery
144
(PREOPERATIVE nebulization group); instillation of saline 20 ml and nebulization of saline 3
145
ml before surgery, and nebulization of ropivacaine 1% 3 ml (30 mg) after surgery
146
(POSTOPERATIVE nebulization group); instillation of ropivacaine 0.5% 20 ml (100 mg) and
147
nebulization of saline 3 ml before surgery, and nebulization of saline 3 ml after surgery
AC C
EP
TE D
M AN U
SC
RI PT
126
ACCEPTED MANUSCRIPT Somaini 8 (INSTILLATION group); instillation of saline 20 ml before surgery, and nebulization of saline 3
149
ml before and after surgery (CONTROL group).
150
Ropivacaine and saline were nebulized using the Aeroneb Pro® system (Aerogen, Galway,
151
Ireland) through a 12-mm port inserted via the umbilical wound. The Aeroneb Pro® device is a
152
high frequency vibrating membrane nebulizer, allowing simultaneous humidification and
153
delivery of local anesthetic, providing cold nebulization by microvibration with more than 80%
154
fine particles with a diameter
