- Email: [email protected]
Epinephrine-Induced Takotsubo Cardiomyopathy During Laparoscopic Myomectomy: Case Report and Review of the Literature
Accepted Manuscript Epinephrine-induced Takotsubo Cardiomyopathy During Laparoscopic Myomectomy: Case Report and Review of the Literature Joseph Nassif, MD, MBA, Hasan Nahouli, BS, Ali Khali, MD, Elie Mikhael, MD, Walid Gharzeddine, MD, Ghina Ghaziri, MD, TC PII:
S1553-4650(17)30290-X
DOI:
10.1016/j.jmig.2017.04.024
Reference:
JMIG 3134
To appear in:
The Journal of Minimally Invasive Gynecology
Received Date: 19 January 2017 Revised Date:
27 April 2017
Accepted Date: 30 April 2017
Please cite this article as: Nassif J, Nahouli H, Khali A, Mikhael E, Gharzeddine W, Ghaziri G, Epinephrine-induced Takotsubo Cardiomyopathy During Laparoscopic Myomectomy: Case Report and Review of the Literature, The Journal of Minimally Invasive Gynecology (2017), doi: 10.1016/ j.jmig.2017.04.024. 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.
Nassif et al.
ACCEPTED MANUSCRIPT Title Page:
Epinephrine-induced Takotsubo Cardiomyopathy During Laparoscopic Myomectomy: Case Report and Review of the Literature Joseph Nassif, MD, MBA, Hasan Nahouli, BS, Ali Khalil, MD, Elie Mikhael, MD,
RI PT
Walid Gharzeddine, MD, Ghina Ghaziri, MD, TC.
SC
Department of Obstetrics and Gynecology (Drs. Nassif, Khalil, Mikhael and Ghaziri), Department of Internal Medicine (Dr. Gharzeddine), Faculty of Medicine (Nahouli), American University of Beirut Medical Center, Riad El-Solh, Beirut, 1107 2020, Lebanon.
M AN U
Precis: We report a unique case of stress-induced cardiomyopathy induced by intramyomal injection of epinephrine during laparoscopic myomectomy.
TE D
Corresponding author contact information:
AC C
EP
Joseph Nassif, MD, MBA Department of Obstetrics and Gynecology Laparoscopy and Minimally Invasive Gynecological Surgery American University of Beirut Medical Center, 7th floor Phone: +961 1 350000 Ext. office: 5636 Ext. clinic: 5840 Pager: 0417 Fax: 00961 1 370 829 Email: [email protected] Keywords: Epinephrine, Laparoscopic Myomectomy, Takotsubo Cardiomyopathy, Myoma.
Declaration of Interest: The authors declare no conflicts of interest. Funding: None.
1
Nassif et al.
ACCEPTED MANUSCRIPT Abstract:
Laparoscopic myomectomy, a minimally invasive procedure performed for the
2
management of uterine leiomyomas involves a challenging aspect: excessive local
3
bleeding. Hemorrhage control during laparoscopic myomectomy could be reached
4
through the use of a wide range of vasoconstrictors including epinephrine.
5
Epinephrine is frequently used for the control of local bleeding during surgery;
6
however, it has been associated with several complications. In this case report, we
7
present a rare and unique case of stress-induced cardiomyopathy, also known as
8
Takotsubo cardiomyopathy (TC), caused by intra-myomal injection of epinephrine
9
during laparoscopic myomectomy. TC is a transient type of cardiomyopathy
M AN U
SC
RI PT
1
associated with a reversible regional systolic and diastolic dysfunction of the left
11
ventricle as well as various abnormal wall motions, and is often indistinguishable
12
from myocardial infarction. TC is more prevalent in women than men and has been
13
linked to supra-physiologic levels of plasma catecholamine. Although epinephrine is
14
an effective vasoconstrictor used to control bleeding, it is potentially associated with
15
adverse events that should be thoroughly investigated within the field of gynecology
16
and its application to laparoscopic myomectomy.
18
EP
AC C
17
TE D
10
2
Nassif et al.
ACCEPTED MANUSCRIPT Case Report Text:
20
Introduction
21
Takotsubo cardiomyopathy (TC) also known as stress-induced cardiomyopathy is an
22
acute yet transient type of cardiomyopathy associated with a reversible regional
23
systolic dysfunction of the left ventricle (1). This stress-induced cardiomyopathy
24
syndrome is reported in the literature as a result of excessive sympathetic stimulation
25
(2). Although this stimulation is commonly reported as endogenous through induction
26
by physical or mental stress, exogenous stimulation through administration of high
27
levels of catecholamine is possible as well (3).
28
In this report, we present a rare case of TC induced by intra-myomal injection of
29
epinephrine during laparoscopic myomectomy, a minimally invasive procedure
30
performed for the management of uterine leiomyomas. The report goes further to
31
discuss the case in light of relevant literature.
M AN U
SC
RI PT
19
TE D
32
Ethical Approval
34
The Institutional Review Board (IRB) committee ruled that approval was not required
35
for this study."
AC C
36
EP
33
37
Case Presentation
38
Medical condition
39
Having experienced the symptom of heavy menstrual bleeding for one complete year
40
while having regular menstrual cycles, a 35-year-old nulligravid patient with BMI of
41
19.3 presented to the clinic. Ultrasound examination revealed the presence of 2 intra-
42
mural fundal uterine leiomyomas of FIGO type 2-5 measuring 3 and 10 cm,
43
respectively. The patient was counseled and consented for laparoscopic myomectomy.
3
Nassif et al.
ACCEPTED MANUSCRIPT 44
The medical history of the patient, who was subjected to appendectomy 24 years ago,
45
revealed no other significant past medical conditions.
46
Laparoscopic myomectomy procedure
48
Having been admitted to the operating room, the patient was ready to undergo the
49
laparoscopic myomectomy. Intra-myomal epinephrine injection is regularly
50
performed during laparoscopic myomectomy procedures at our medical center. The
51
intra-myomal epinephrine injection is used to decrease blood loss during laparoscopic
52
myomectomy procedure. The injection is constituted of 1 mg of epinephrine diluted in
53
60 ml of normal saline and usually injected directly inside each leiomyoma under
54
vision using a Veress needle. The injection is usually preceded by an aspiration test to
55
check the appropriate insertion location of the needle that should not be inserted
56
inside any vessel.
57
Intraoperatively, 0.1 mg of epinephrine was injected first inside the 3 cm fundal
58
anterior leiomyoma after performing an aspiration test. This injection was
59
immediately followed by an increase in blood pressure reaching values as high as
60
200/120 mmHg, accompanied by tachycardia reaching 130 beats per minute.
61
Additionally, oxygen saturation dropped to 90% necessitating the application of
62
positive end expiratory pressure (12 cm of water) that eventually succeeded in
63
restoring a saturation of 100%. After the removal of the first leiomyoma, 0.2 mg of
64
epinephrine was injected inside the 10 cm posterior fundal leiomyoma. The operation
65
was otherwise uncomplicated and no blood loss was worth noting.
AC C
EP
TE D
M AN U
SC
RI PT
47
66 67
Post-laparoscopic myomectomy complications
4
Nassif et al.
ACCEPTED MANUSCRIPT
Shortly after being transferred from the operating room to the recovery room, the
69
patient reported shortness of breath, cough and fatigue, yet she denied chest pain.
70
Vital measures indicated a blood pressure of 96/50 mmHg, pulse of 60 bpm and
71
oxygen saturation of 85%. The electrocardiogram (EKG) showed normal sinus
72
rhythm with no ST segment changes. The patient developed bilateral decreased air
73
entry and fine expiratory crackles on lung exam, while heart sounds were normal with
74
no murmurs.
75
The patient was immediately placed on bi-level positive airway pressure; chest x-ray
76
was done revealing mild lung congestion that was treated with 40 mg of intra-venous
77
furosemide. After taking these immediate measures, the saturation improved
78
gradually and was restored to 95% within a few minutes. An urgent echocardiogram
79
was subsequently performed and revealed severe left ventricular hypokinesia of mid-
80
septum, mid-lateral, mid-anteroseptal and mid-posterior walls. The left ventricular
81
ejection fraction was estimated as 40-44%. Laboratory tests performed showed a
82
positive troponin T level of 0.271 ng/mL with an elevated CK-MB and CPK reaching
83
7.4 µg/L and 201 IU/L, respectively. The pro-BNP was detected as 156 pg/mL.
84
Accordingly, the working diagnosis was agreed to be stress-induced cardiomyopathy,
85
also known as Takotsubo syndrome. The patient was consequently transferred to the
86
cardiac care unit (CCU) for continuous monitoring, and the he symptoms related to
87
the diagnosis started to subside within a few hours after admission to the CCU. The
88
patient, whose troponin T level dropped to 0.146 ng/mL, became asymptomatic 12
89
hours later without the use of any supplemental oxygen.
90
A subsequent follow-up echocardiogram done 24 hours after the episode, showed a
91
marked improvement of the wall motion anomalies; however, a localized area of
AC C
EP
TE D
M AN U
SC
RI PT
68
5
Nassif et al.
ACCEPTED MANUSCRIPT 92
hypokinesia in the mid-posterior wall remained persistent with an estimated left
93
ventricular ejection fraction of 55-59%.
94
Comment
RI PT
95 96
One of the most challenging problems faced when performing myomectomy is
98
hemorrhage control. The literature reports extensively on hemorrhage control during
99
myomectomy describing several interventions that have potential ability to limit intra-
100
operative blood loss (4-6). For example, the injection of diluted epinephrine during
101
laparoscopic myomectomy has been shown to significantly decrease blood loss (6),
102
through the induction of vasoconstriction of the uterine tissue (7). Similarly, in a
103
systematic review of randomized controlled trials examining the reduction of
104
hemorrhage during myomectomy for uterine fibroids by Kongnyuy et al., the mix of
105
bupivacaine plus epinephrine and vasopressin was documented as a local
106
vasoconstrictor that plays a significant role in reducing excessive local bleeding when
107
injected around the myoma during a myomectomy (4).
108
Few studies designed to assess the safety and efficacy of epinephrine in reducing
109
operative blood loss in laparoscopic myomectomies exist in the literature. In a
110
randomized trial designed by Song et al. to compare the use of vasopressin versus
111
epinephrine in reducing hemorrhage during myomectomy, adverse events associated
112
with the use of intra-myometrial epinephrine were described (Table 1) (8). The study
113
reported that the most prevalent adverse events associated with the use of intra-
114
myometrial epinephrine were transient and insignificant such as an increase in
115
systolic and diastolic blood pressure and heart rate in 13% of the patients, with similar
116
efficacy between both medications regarding operative blood loss, operative time,
AC C
EP
TE D
M AN U
SC
97
6
Nassif et al.
ACCEPTED MANUSCRIPT
subjective surgical difficulty, postoperative pain and complications (8). Another
118
randomized controlled trial by Zullo et al. showed that the injection of both
119
bupivacaine and epinephrine in laparoscopic myomectomy significantly reduced
120
blood loss, total operative and enucleation time, degree of surgical difficulty, and
121
postoperative pain (Table 1) (6). On the other hand, Litta et al. compared the use of
122
the harmonic device alone versus the use of electrosurgery and epinephrine during
123
laparoscopic myomectomy to find that the harmonic device was associated with
124
significantly less operative and total blood loss, shorter operative time, and lower
125
degree of pain intensity, without any cardiovascular adverse events (9).
SC
RI PT
117
NOTE TO EDITOR: INSERT TABLE 1 HERE
127
Focusing particularly on reported cardiac adverse event cases related to the use of
128
vasoconstrictors during myomectomy, few case reports documented adverse events
129
such as bradycardia, severe vasospasm, or cardiac arrest caused by the use of intra-
130
myometrial injection of vasopressin during myomectomy (10, 11). Based on the
131
literature and to the best of our knowledge, only one case report highlighted cardiac
132
adverse events associated with the use of local epinephrine in surgery (12). The report
133
documented a case of stress-induced cardiomyopathy upon local use of epinephrine,
134
and suggested a potential association of epinephrine with various complications such
135
as pulmonary edema, reversible cardiomyopathy, and cardiac arrest (12). A few other
136
cases of TC have been reported in patients who received intravenous epinephrine for
137
the treatment of anaphylaxis or severe allergy (13, 14). Nevertheless, there is a dearth
138
of evidence about complications related to the use of epinephrine in gynecology, more
139
specifically during laparoscopic myomectomy.
140
Our patient experienced TC upon intra-myomal injection of epinephrine during
141
laparoscopic myomectomy, a case rarely documented in the literature. TC also known
AC C
EP
TE D
M AN U
126
7
Nassif et al.
ACCEPTED MANUSCRIPT
as stress-induced cardiomyopathy, is a transient cardiomyopathy associated with a
143
reversible regional systolic and diastolic dysfunction of the left ventricle as well as
144
various abnormal wall motions (1, 15). Its clinical presentation, biomarker profiles
145
and electrocardiographic findings are often indistinguishable from myocardial
146
infarction (16). While the exact pathophysiology of TC is still not clearly understood,
147
it has been linked to supra-physiologic levels of plasma catecholamine and potentially
148
presents in patients with neuropsychiatric disorders (2). TC is more prevalent among
149
women than men, and more precisely affects women of older age (15). Although the
150
cause of TC remains unclear, it has been reported that the brain–heart axis plays a
151
central role in the pathogenesis of this disease (15, 17, 18); the symptoms are
152
predominantly preceded by a physical or emotional trigger (19), yet may also occur
153
without any evident trigger (15).
154
M AN U
SC
RI PT
142
Conclusion
156
Although epinephrine has been shown to reduce operative blood loss in laparoscopic
157
myomectomy, attention should be drawn to the potential adverse events associated
158
with its use in gynecologic surgery (12). The incidents of cardiovascular adverse
159
events
160
cardiomyopathy should be further investigated by experts in the field.
as
transient
tachycardia,
AC C
such
EP
TE D
155
8
hypertension,
and
stress-induced
Nassif et al.
ACCEPTED MANUSCRIPT 161
References:
162
1.
163
or takotsubo cardiomyopathy: a systematic review. European Heart Journal. 2006; 27:1523-9.
164
2.
165
Neurohumoral features of myocardial stunning due to sudden emotional stress. New England
166
Journal of Medicine. 2005; 352:539-48.
167
3.
168
cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced
169
acute myocardial stunning. Nature Clinical Practice Cardiovascular Medicine. 2008; 5:22-9.
170
4.
171
to reduce hemorrhage during myomectomy for uterine fibroids. International Journal of
172
Gynecology & Obstetrics. 2008; 100:4-9.
173
5.
174
for fibroids. Cochrane Database of Systematic Reviews. 2014.
175
6.
176
epinephrine for laparoscopic myomectomy: a randomized placebo-controlled trial. Obstetrics &
177
Gynecology. 2004; 104:243-9.
178
7.
179
in vaginal hysterectomies. Obstetrics & Gynecology. 1983; 61:271-4.
180
8.
181
reduce haemorrhage during myomectomy: a randomized controlled trial. European Journal of
182
Obstetrics & Gynecology and Reproductive Biology. 2015; 195:177-81.
183
9.
184
controlled study comparing harmonic versus electrosurgery in laparoscopic myomectomy.
185
Fertility and sterility. 2010; 94:1882-6.
Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome
RI PT
Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al.
SC
Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo)
M AN U
Kongnyuy EJ, Broek N, Wiysonge C. A systematic review of randomized controlled trials
Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy
TE D
Zullo F, Palomba S, Corea D, Pellicano M, Russo T, Falbo A, et al. Bupivacaine plus
EP
England GT, Randall HW, Graves Wl. Impairment of tissue defenses by vasoconstrictors
AC C
Song T, Kim M, Kim M-L, Jung Y, Yun B, Seong S. Use of vasopressin vs epinephrine to
Litta P, Fantinato S, Calonaci F, Cosmi E, Filippeschi M, Zerbetto I, et al. A randomized
9
Nassif et al.
ACCEPTED MANUSCRIPT 186
10.
Butala BP, Shah VR, Parikh BK, Jayaprakash J, Kalo J. Bradycardia and severe vasospasm
187
caused by intramyometrial injection of vasopressin during myomectomy. Saudi Journal of
188
Anaesthesia. 2014; 8:396.
189
11.
190
intramyometrial injection of vasopressin during a laparoscopically assisted myomectomy.
191
Obstetrics & Gynecology. 2009; 113:484-6.
192
12.
193
Epinephrine Use-A case report. Korean Journal of Anesthesiology. 2008; 54:581-4.
194
13.
195
caused by epinephrine-treated bee sting anaphylaxis: a case report. Journal of Medical Case
196
Reports. 2015; 9:1.
197
14.
198
shock. A report of two cases. Annales de Cardiologie et D'angeiologie. 2011; 60:113-7.
199
15.
200
features and outcomes of takotsubo (stress) cardiomyopathy. New England Journal of Medicine.
201
2015; 373:929-38.
202
16.
203
cardiomyopathy): a mimic of acute myocardial infarction. American Heart Journal. 2008;
204
155:408-17.
205
17.
206
18.
207
for brain activation in patients with takotsubo cardiomyopathy. Circulation Journal. 2014; 78:
208
256-8.
209
19.
210
Myocardial Infarction Investigations in Japan. Transient left ventricular apical ballooning
211
without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial
212
infarction. J Am Coll Cardiol. 2001; 38:11-8.
RI PT
Hobo R, Netsu S, Koyasu Y, Tsutsumi O. Bradycardia and cardiac arrest caused by
SC
Cho CK, Jung SM, Kim JY, Kwon HU, Kang PS. Stress Induced Cardiomyopathy after Local
M AN U
Ghanim D, Adler Z, Qarawani D, Kusniec F, Amir O, Carasso S. Takotsubo cardiomyopathy
Verdier F, Petitjeans F, Griffet V, Caignault J, Guerard S. Heart failure and anaphylactic
TE D
Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical
EP
Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress
AC C
Samuels MA. The brain–heart connection. Circulation Journal. 2007; 116: 77-84. Suzuki H, Matsumoto Y, Kaneta T, Sugimura K, Takahashi J, Fukumoto Y, et al. Evidence
Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, et al. Angina Pectoris-
10
Nassif et al.
ACCEPTED MANUSCRIPT Table Legend:
214
Table 1: dose and adverse effects of epinephrine used in different studies.
AC C
EP
TE D
M AN U
SC
RI PT
213
11
ACCEPTED MANUSCRIPT Table 1 : dose and adverse effects of epinephrine used in different studies.
Investigators
Maximal dose per
Dilution
Adverse reactions
patient
epinephrine (1/2 vial of 1 mg/ml concentration) in 50
solution (Litta et al., 2010)
0.5 mg of
TE D
epinephrine (1/2 vial of 1 mg/ml
concentration) in 50
EP
ml of saline
AC C
solution
diastolic
hypertension and
(0.2 mg)
tachycardia
M AN U
ml of saline
diluted solution
13% had transient
RI PT
20 ml of the
0.5 mg of
SC
(Song et al., 2015)
Not available
transient systolic and diastolic hypertension and tachycardia
ACCEPTED MANUSCRIPT Precis: We report a unique case of stress-induced cardiomyopathy induced by intra-
AC C
EP
TE D
M AN U
SC
RI PT
myomal injection of epinephrine during laparoscopic myomectomy.
S1553-4650(17)30290-X
DOI:
10.1016/j.jmig.2017.04.024
Reference:
JMIG 3134
To appear in:
The Journal of Minimally Invasive Gynecology
Received Date: 19 January 2017 Revised Date:
27 April 2017
Accepted Date: 30 April 2017
Please cite this article as: Nassif J, Nahouli H, Khali A, Mikhael E, Gharzeddine W, Ghaziri G, Epinephrine-induced Takotsubo Cardiomyopathy During Laparoscopic Myomectomy: Case Report and Review of the Literature, The Journal of Minimally Invasive Gynecology (2017), doi: 10.1016/ j.jmig.2017.04.024. 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.
Nassif et al.
ACCEPTED MANUSCRIPT Title Page:
Epinephrine-induced Takotsubo Cardiomyopathy During Laparoscopic Myomectomy: Case Report and Review of the Literature Joseph Nassif, MD, MBA, Hasan Nahouli, BS, Ali Khalil, MD, Elie Mikhael, MD,
RI PT
Walid Gharzeddine, MD, Ghina Ghaziri, MD, TC.
SC
Department of Obstetrics and Gynecology (Drs. Nassif, Khalil, Mikhael and Ghaziri), Department of Internal Medicine (Dr. Gharzeddine), Faculty of Medicine (Nahouli), American University of Beirut Medical Center, Riad El-Solh, Beirut, 1107 2020, Lebanon.
M AN U
Precis: We report a unique case of stress-induced cardiomyopathy induced by intramyomal injection of epinephrine during laparoscopic myomectomy.
TE D
Corresponding author contact information:
AC C
EP
Joseph Nassif, MD, MBA Department of Obstetrics and Gynecology Laparoscopy and Minimally Invasive Gynecological Surgery American University of Beirut Medical Center, 7th floor Phone: +961 1 350000 Ext. office: 5636 Ext. clinic: 5840 Pager: 0417 Fax: 00961 1 370 829 Email: [email protected] Keywords: Epinephrine, Laparoscopic Myomectomy, Takotsubo Cardiomyopathy, Myoma.
Declaration of Interest: The authors declare no conflicts of interest. Funding: None.
1
Nassif et al.
ACCEPTED MANUSCRIPT Abstract:
Laparoscopic myomectomy, a minimally invasive procedure performed for the
2
management of uterine leiomyomas involves a challenging aspect: excessive local
3
bleeding. Hemorrhage control during laparoscopic myomectomy could be reached
4
through the use of a wide range of vasoconstrictors including epinephrine.
5
Epinephrine is frequently used for the control of local bleeding during surgery;
6
however, it has been associated with several complications. In this case report, we
7
present a rare and unique case of stress-induced cardiomyopathy, also known as
8
Takotsubo cardiomyopathy (TC), caused by intra-myomal injection of epinephrine
9
during laparoscopic myomectomy. TC is a transient type of cardiomyopathy
M AN U
SC
RI PT
1
associated with a reversible regional systolic and diastolic dysfunction of the left
11
ventricle as well as various abnormal wall motions, and is often indistinguishable
12
from myocardial infarction. TC is more prevalent in women than men and has been
13
linked to supra-physiologic levels of plasma catecholamine. Although epinephrine is
14
an effective vasoconstrictor used to control bleeding, it is potentially associated with
15
adverse events that should be thoroughly investigated within the field of gynecology
16
and its application to laparoscopic myomectomy.
18
EP
AC C
17
TE D
10
2
Nassif et al.
ACCEPTED MANUSCRIPT Case Report Text:
20
Introduction
21
Takotsubo cardiomyopathy (TC) also known as stress-induced cardiomyopathy is an
22
acute yet transient type of cardiomyopathy associated with a reversible regional
23
systolic dysfunction of the left ventricle (1). This stress-induced cardiomyopathy
24
syndrome is reported in the literature as a result of excessive sympathetic stimulation
25
(2). Although this stimulation is commonly reported as endogenous through induction
26
by physical or mental stress, exogenous stimulation through administration of high
27
levels of catecholamine is possible as well (3).
28
In this report, we present a rare case of TC induced by intra-myomal injection of
29
epinephrine during laparoscopic myomectomy, a minimally invasive procedure
30
performed for the management of uterine leiomyomas. The report goes further to
31
discuss the case in light of relevant literature.
M AN U
SC
RI PT
19
TE D
32
Ethical Approval
34
The Institutional Review Board (IRB) committee ruled that approval was not required
35
for this study."
AC C
36
EP
33
37
Case Presentation
38
Medical condition
39
Having experienced the symptom of heavy menstrual bleeding for one complete year
40
while having regular menstrual cycles, a 35-year-old nulligravid patient with BMI of
41
19.3 presented to the clinic. Ultrasound examination revealed the presence of 2 intra-
42
mural fundal uterine leiomyomas of FIGO type 2-5 measuring 3 and 10 cm,
43
respectively. The patient was counseled and consented for laparoscopic myomectomy.
3
Nassif et al.
ACCEPTED MANUSCRIPT 44
The medical history of the patient, who was subjected to appendectomy 24 years ago,
45
revealed no other significant past medical conditions.
46
Laparoscopic myomectomy procedure
48
Having been admitted to the operating room, the patient was ready to undergo the
49
laparoscopic myomectomy. Intra-myomal epinephrine injection is regularly
50
performed during laparoscopic myomectomy procedures at our medical center. The
51
intra-myomal epinephrine injection is used to decrease blood loss during laparoscopic
52
myomectomy procedure. The injection is constituted of 1 mg of epinephrine diluted in
53
60 ml of normal saline and usually injected directly inside each leiomyoma under
54
vision using a Veress needle. The injection is usually preceded by an aspiration test to
55
check the appropriate insertion location of the needle that should not be inserted
56
inside any vessel.
57
Intraoperatively, 0.1 mg of epinephrine was injected first inside the 3 cm fundal
58
anterior leiomyoma after performing an aspiration test. This injection was
59
immediately followed by an increase in blood pressure reaching values as high as
60
200/120 mmHg, accompanied by tachycardia reaching 130 beats per minute.
61
Additionally, oxygen saturation dropped to 90% necessitating the application of
62
positive end expiratory pressure (12 cm of water) that eventually succeeded in
63
restoring a saturation of 100%. After the removal of the first leiomyoma, 0.2 mg of
64
epinephrine was injected inside the 10 cm posterior fundal leiomyoma. The operation
65
was otherwise uncomplicated and no blood loss was worth noting.
AC C
EP
TE D
M AN U
SC
RI PT
47
66 67
Post-laparoscopic myomectomy complications
4
Nassif et al.
ACCEPTED MANUSCRIPT
Shortly after being transferred from the operating room to the recovery room, the
69
patient reported shortness of breath, cough and fatigue, yet she denied chest pain.
70
Vital measures indicated a blood pressure of 96/50 mmHg, pulse of 60 bpm and
71
oxygen saturation of 85%. The electrocardiogram (EKG) showed normal sinus
72
rhythm with no ST segment changes. The patient developed bilateral decreased air
73
entry and fine expiratory crackles on lung exam, while heart sounds were normal with
74
no murmurs.
75
The patient was immediately placed on bi-level positive airway pressure; chest x-ray
76
was done revealing mild lung congestion that was treated with 40 mg of intra-venous
77
furosemide. After taking these immediate measures, the saturation improved
78
gradually and was restored to 95% within a few minutes. An urgent echocardiogram
79
was subsequently performed and revealed severe left ventricular hypokinesia of mid-
80
septum, mid-lateral, mid-anteroseptal and mid-posterior walls. The left ventricular
81
ejection fraction was estimated as 40-44%. Laboratory tests performed showed a
82
positive troponin T level of 0.271 ng/mL with an elevated CK-MB and CPK reaching
83
7.4 µg/L and 201 IU/L, respectively. The pro-BNP was detected as 156 pg/mL.
84
Accordingly, the working diagnosis was agreed to be stress-induced cardiomyopathy,
85
also known as Takotsubo syndrome. The patient was consequently transferred to the
86
cardiac care unit (CCU) for continuous monitoring, and the he symptoms related to
87
the diagnosis started to subside within a few hours after admission to the CCU. The
88
patient, whose troponin T level dropped to 0.146 ng/mL, became asymptomatic 12
89
hours later without the use of any supplemental oxygen.
90
A subsequent follow-up echocardiogram done 24 hours after the episode, showed a
91
marked improvement of the wall motion anomalies; however, a localized area of
AC C
EP
TE D
M AN U
SC
RI PT
68
5
Nassif et al.
ACCEPTED MANUSCRIPT 92
hypokinesia in the mid-posterior wall remained persistent with an estimated left
93
ventricular ejection fraction of 55-59%.
94
Comment
RI PT
95 96
One of the most challenging problems faced when performing myomectomy is
98
hemorrhage control. The literature reports extensively on hemorrhage control during
99
myomectomy describing several interventions that have potential ability to limit intra-
100
operative blood loss (4-6). For example, the injection of diluted epinephrine during
101
laparoscopic myomectomy has been shown to significantly decrease blood loss (6),
102
through the induction of vasoconstriction of the uterine tissue (7). Similarly, in a
103
systematic review of randomized controlled trials examining the reduction of
104
hemorrhage during myomectomy for uterine fibroids by Kongnyuy et al., the mix of
105
bupivacaine plus epinephrine and vasopressin was documented as a local
106
vasoconstrictor that plays a significant role in reducing excessive local bleeding when
107
injected around the myoma during a myomectomy (4).
108
Few studies designed to assess the safety and efficacy of epinephrine in reducing
109
operative blood loss in laparoscopic myomectomies exist in the literature. In a
110
randomized trial designed by Song et al. to compare the use of vasopressin versus
111
epinephrine in reducing hemorrhage during myomectomy, adverse events associated
112
with the use of intra-myometrial epinephrine were described (Table 1) (8). The study
113
reported that the most prevalent adverse events associated with the use of intra-
114
myometrial epinephrine were transient and insignificant such as an increase in
115
systolic and diastolic blood pressure and heart rate in 13% of the patients, with similar
116
efficacy between both medications regarding operative blood loss, operative time,
AC C
EP
TE D
M AN U
SC
97
6
Nassif et al.
ACCEPTED MANUSCRIPT
subjective surgical difficulty, postoperative pain and complications (8). Another
118
randomized controlled trial by Zullo et al. showed that the injection of both
119
bupivacaine and epinephrine in laparoscopic myomectomy significantly reduced
120
blood loss, total operative and enucleation time, degree of surgical difficulty, and
121
postoperative pain (Table 1) (6). On the other hand, Litta et al. compared the use of
122
the harmonic device alone versus the use of electrosurgery and epinephrine during
123
laparoscopic myomectomy to find that the harmonic device was associated with
124
significantly less operative and total blood loss, shorter operative time, and lower
125
degree of pain intensity, without any cardiovascular adverse events (9).
SC
RI PT
117
NOTE TO EDITOR: INSERT TABLE 1 HERE
127
Focusing particularly on reported cardiac adverse event cases related to the use of
128
vasoconstrictors during myomectomy, few case reports documented adverse events
129
such as bradycardia, severe vasospasm, or cardiac arrest caused by the use of intra-
130
myometrial injection of vasopressin during myomectomy (10, 11). Based on the
131
literature and to the best of our knowledge, only one case report highlighted cardiac
132
adverse events associated with the use of local epinephrine in surgery (12). The report
133
documented a case of stress-induced cardiomyopathy upon local use of epinephrine,
134
and suggested a potential association of epinephrine with various complications such
135
as pulmonary edema, reversible cardiomyopathy, and cardiac arrest (12). A few other
136
cases of TC have been reported in patients who received intravenous epinephrine for
137
the treatment of anaphylaxis or severe allergy (13, 14). Nevertheless, there is a dearth
138
of evidence about complications related to the use of epinephrine in gynecology, more
139
specifically during laparoscopic myomectomy.
140
Our patient experienced TC upon intra-myomal injection of epinephrine during
141
laparoscopic myomectomy, a case rarely documented in the literature. TC also known
AC C
EP
TE D
M AN U
126
7
Nassif et al.
ACCEPTED MANUSCRIPT
as stress-induced cardiomyopathy, is a transient cardiomyopathy associated with a
143
reversible regional systolic and diastolic dysfunction of the left ventricle as well as
144
various abnormal wall motions (1, 15). Its clinical presentation, biomarker profiles
145
and electrocardiographic findings are often indistinguishable from myocardial
146
infarction (16). While the exact pathophysiology of TC is still not clearly understood,
147
it has been linked to supra-physiologic levels of plasma catecholamine and potentially
148
presents in patients with neuropsychiatric disorders (2). TC is more prevalent among
149
women than men, and more precisely affects women of older age (15). Although the
150
cause of TC remains unclear, it has been reported that the brain–heart axis plays a
151
central role in the pathogenesis of this disease (15, 17, 18); the symptoms are
152
predominantly preceded by a physical or emotional trigger (19), yet may also occur
153
without any evident trigger (15).
154
M AN U
SC
RI PT
142
Conclusion
156
Although epinephrine has been shown to reduce operative blood loss in laparoscopic
157
myomectomy, attention should be drawn to the potential adverse events associated
158
with its use in gynecologic surgery (12). The incidents of cardiovascular adverse
159
events
160
cardiomyopathy should be further investigated by experts in the field.
as
transient
tachycardia,
AC C
such
EP
TE D
155
8
hypertension,
and
stress-induced
Nassif et al.
ACCEPTED MANUSCRIPT 161
References:
162
1.
163
or takotsubo cardiomyopathy: a systematic review. European Heart Journal. 2006; 27:1523-9.
164
2.
165
Neurohumoral features of myocardial stunning due to sudden emotional stress. New England
166
Journal of Medicine. 2005; 352:539-48.
167
3.
168
cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced
169
acute myocardial stunning. Nature Clinical Practice Cardiovascular Medicine. 2008; 5:22-9.
170
4.
171
to reduce hemorrhage during myomectomy for uterine fibroids. International Journal of
172
Gynecology & Obstetrics. 2008; 100:4-9.
173
5.
174
for fibroids. Cochrane Database of Systematic Reviews. 2014.
175
6.
176
epinephrine for laparoscopic myomectomy: a randomized placebo-controlled trial. Obstetrics &
177
Gynecology. 2004; 104:243-9.
178
7.
179
in vaginal hysterectomies. Obstetrics & Gynecology. 1983; 61:271-4.
180
8.
181
reduce haemorrhage during myomectomy: a randomized controlled trial. European Journal of
182
Obstetrics & Gynecology and Reproductive Biology. 2015; 195:177-81.
183
9.
184
controlled study comparing harmonic versus electrosurgery in laparoscopic myomectomy.
185
Fertility and sterility. 2010; 94:1882-6.
Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome
RI PT
Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al.
SC
Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (Takotsubo)
M AN U
Kongnyuy EJ, Broek N, Wiysonge C. A systematic review of randomized controlled trials
Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy
TE D
Zullo F, Palomba S, Corea D, Pellicano M, Russo T, Falbo A, et al. Bupivacaine plus
EP
England GT, Randall HW, Graves Wl. Impairment of tissue defenses by vasoconstrictors
AC C
Song T, Kim M, Kim M-L, Jung Y, Yun B, Seong S. Use of vasopressin vs epinephrine to
Litta P, Fantinato S, Calonaci F, Cosmi E, Filippeschi M, Zerbetto I, et al. A randomized
9
Nassif et al.
ACCEPTED MANUSCRIPT 186
10.
Butala BP, Shah VR, Parikh BK, Jayaprakash J, Kalo J. Bradycardia and severe vasospasm
187
caused by intramyometrial injection of vasopressin during myomectomy. Saudi Journal of
188
Anaesthesia. 2014; 8:396.
189
11.
190
intramyometrial injection of vasopressin during a laparoscopically assisted myomectomy.
191
Obstetrics & Gynecology. 2009; 113:484-6.
192
12.
193
Epinephrine Use-A case report. Korean Journal of Anesthesiology. 2008; 54:581-4.
194
13.
195
caused by epinephrine-treated bee sting anaphylaxis: a case report. Journal of Medical Case
196
Reports. 2015; 9:1.
197
14.
198
shock. A report of two cases. Annales de Cardiologie et D'angeiologie. 2011; 60:113-7.
199
15.
200
features and outcomes of takotsubo (stress) cardiomyopathy. New England Journal of Medicine.
201
2015; 373:929-38.
202
16.
203
cardiomyopathy): a mimic of acute myocardial infarction. American Heart Journal. 2008;
204
155:408-17.
205
17.
206
18.
207
for brain activation in patients with takotsubo cardiomyopathy. Circulation Journal. 2014; 78:
208
256-8.
209
19.
210
Myocardial Infarction Investigations in Japan. Transient left ventricular apical ballooning
211
without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial
212
infarction. J Am Coll Cardiol. 2001; 38:11-8.
RI PT
Hobo R, Netsu S, Koyasu Y, Tsutsumi O. Bradycardia and cardiac arrest caused by
SC
Cho CK, Jung SM, Kim JY, Kwon HU, Kang PS. Stress Induced Cardiomyopathy after Local
M AN U
Ghanim D, Adler Z, Qarawani D, Kusniec F, Amir O, Carasso S. Takotsubo cardiomyopathy
Verdier F, Petitjeans F, Griffet V, Caignault J, Guerard S. Heart failure and anaphylactic
TE D
Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical
EP
Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress
AC C
Samuels MA. The brain–heart connection. Circulation Journal. 2007; 116: 77-84. Suzuki H, Matsumoto Y, Kaneta T, Sugimura K, Takahashi J, Fukumoto Y, et al. Evidence
Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, et al. Angina Pectoris-
10
Nassif et al.
ACCEPTED MANUSCRIPT Table Legend:
214
Table 1: dose and adverse effects of epinephrine used in different studies.
AC C
EP
TE D
M AN U
SC
RI PT
213
11
ACCEPTED MANUSCRIPT Table 1 : dose and adverse effects of epinephrine used in different studies.
Investigators
Maximal dose per
Dilution
Adverse reactions
patient
epinephrine (1/2 vial of 1 mg/ml concentration) in 50
solution (Litta et al., 2010)
0.5 mg of
TE D
epinephrine (1/2 vial of 1 mg/ml
concentration) in 50
EP
ml of saline
AC C
solution
diastolic
hypertension and
(0.2 mg)
tachycardia
M AN U
ml of saline
diluted solution
13% had transient
RI PT
20 ml of the
0.5 mg of
SC
(Song et al., 2015)
Not available
transient systolic and diastolic hypertension and tachycardia
ACCEPTED MANUSCRIPT Precis: We report a unique case of stress-induced cardiomyopathy induced by intra-
AC C
EP
TE D
M AN U
SC
RI PT
myomal injection of epinephrine during laparoscopic myomectomy.