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\begin{document}

\title{Anesthesia using remimazolam during coronary artery bypass surgery in a
patient with decreased left ventricular function}



\author[1]{Shingo Narumi}%
\author[2]{Yusuke Ishida}%
\author[1]{Sae Igarashi}%
\author[1]{Shunya Sekiguchi}%
\author[1]{AYA KAWACHI}%
\author[1]{Mikiko Tomino}%
\affil[1]{Tokyo Medical University Hospital}%
\affil[2]{Tokyo Medical University}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\textbf{Anesthesia using remimazolam during coronary artery bypass
surgery in a patient with decreased left ventricular function}

Shingo Narumi, Yusuke Ishida, Sae Igarashi, Shunya Sekiguchi, Aya
Kawachi, and Mikiko Tomino

Department of Anesthesiology, Tokyo Medical University, 6-7-1
Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

\textbf{Corresponding author:} Yusuke Ishida

Department of Anesthesiology

Tokyo Medical University

6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

Tel.: +81-03-3342-6111; Fax: +81-03-5381-6650

Email: yishida14anes@gmail.com



\textbf{ABSTRACT}

Some patients who undergo cardiac surgery have reduced cardiac function,
which can often make anesthesia management difficult owing to severe
hypotension at the time of anesthesia induction. Therefore, it is
important to select drugs that cause minimal circulatory depression. On
the other hand, in 2020, the use of remimazolam, a short-acting
benzodiazepine sedative, was approved in Japan, and reports of its use
in various patients have been increasing. This drug has the
characteristic of causing minimal effects on circulation. We here report
the safe use of remimazolam in the anesthesia management of a patient
with decreased cardiac function who was diagnosed as having angina
pectoris. The patient was a 73-year-old man scheduled for coronary
artery bypass graft (CABG) surgery. Remimazolam was used for sedation
purposes during anesthesia induction. During surgery, there were no
significant hemodynamic changes and the patient remained in stable
cardiovascular condition. Our present case indicates that remimazolam
can be considered as an option for anesthesia management in CABG for
patients with decreased cardiac function.

\textbf{Keywords}

angina, coronary artery bypass graft (CABG), cardiac output, ejection
fraction, remimazolam



\textbf{Key clinical message}

Remimazolam is a new benzodiazepine sedative and has the characteristic
of causing minimal effects on circulation. This case indicates that it
can be considered as an option for anesthesia management of patients
with decreased cardiac function.

\textbf{Background}

In the management of anesthesia during cardiac surgery, it is important
to stably maintain the patient's cardiovascular function throughout the
operation. Therefore, it is necessary to carefully evaluate the
patient's cardiovascular function before surgery, monitor their general
condition, and choose sedatives and analgesics carefully during
anesthesia management. On the other hand, remimazolam, an
ultra-short-acting benzodiazepine, has been available for use in Japan
since 2020 {[}1{]}. This drug has a short half-life and causes minimal
circulatory depression {[}2{]}, making it a suitable sedative for
patients with decreased cardiac function. In this report, we used
remimazolam safely in the anesthesia management of coronary artery
bypass graft (CABG) surgery, and present our findings. Written informed
consent was obtained from the patient to publish this case report.

\textbf{Case presentation}

The patient was a 73-year-old man with a height of 170 cm and weight of
58 kg. He had a history of diabetes and chronic kidney disease and was
being followed up by the nephrology department of our hospital. This
time, he was admitted to the coronary care unit for fluid control owing
to acute exacerbation of chronic kidney disease and a diagnosis of
congestive heart failure. Electrocardiography displayed flat T-waves in
the inferior leads (II, III, and aVF leads), and negative T-waves were
observed in the precordial leads (V1--V4 leads). Additionally,
echocardiography demonstrated a reduced left ventricular ejection
fraction of about 30\% and diffuse wall-motion abnormalities. On stress
myocardial scintigraphy, suspected ischemic findings were observed in
the distal region of the left anterior descending artery and the right
coronary artery, and coronary angiography (CAG) was performed. The
patient was found to have triple vessel disease on the CAG and was
scheduled for a CABG. Owing to the patient's low cardiac function, the
strategy of on-pump beating CABG was adopted. In addition, anesthesia
management of the patient was considered carefully, and it was decided
that drugs that cause minimal circulatory depression should be used as
much as possible.

Anesthesia was induced with remimazolam at 12 mg/kg/hr, remifentanil at
0.3 \selectlanguage{greek}µ\selectlanguage{english}g/kg/min, and rocuronium at 50 mg. Anesthesia maintenance was
performed with remimazolam at 1 mg/kg/hr, remifentanil at 0.25
\selectlanguage{greek}µ\selectlanguage{english}g/kg/min, and rocuronium at 20 mg/hr. An 8 mm-endotracheal tube was
used for intubation. Phenylephrine (0.05 mg) was administered as needed
for hypotension. During the surgery, monitoring was performed with
invasive arterial pressure, peripheral blood oxygen saturation, central
venous pressure, Patient State Index (PSI), regional oxygen saturation,
and transesophageal echocardiography. Continuous monitoring of cardiac
output was also performed using the FloTrac Sensor (Edwards
Lifesciences Co., Tokyo, Japan). (Figure.1) From induction to just
before the cardiopulmonary bypass (CPB), the cardiac output and cardiac
index remained at about 3.0 to 4.0 L/min and 1.8 to 2.5
L/min/m\textsuperscript{2}, respectively. Stroke volume variation (SVV)
remained at about 15\%. In addition, administration of the coronary
vasodilator nicorandil was started at a rate of 3 mg/hr, and isosorbide
dinitrate at a rate of 1 mg/hr from the time of induction. The patient
underwent on-pump beating CABG without any significant hemodynamic
instability during the CPB. The grafts used were the left internal
thoracic artery, left radial artery, and great saphenous vein. Five
branches were anastomosed. During separation from the CPB, a continuous
infusion of dobutamine at a rate of 0.5 \selectlanguage{greek}µ\selectlanguage{english}g/kg/min was administered. The
patient's hemodynamic status remained stable without any significant
problems even after weaning off from the CPB, and anesthesia was
successfully maintained. After separation from the CPB, remimazolam was
continuously administered at a rate of 0.7 to 0.8 mg/kg/hr. We were
using the PSI as an indicator of sedation, and PSI values remained at
about 30 to 40. Anesthesia time was 8 hours and 32 minutes, surgical
time was 7 hours and 20 minutes, and CPB time was 3 hours and 43
minutes. The total amount of fluid administered was 1,550 mL, and the
amount of bleeding was 1,090 mL. The patient received a transfusion of 4
units of red blood cell concentrate and 1,000 mL of 5\% albumin
products. Upon admission to the intensive care unit, the patient was
weaned off mechanical ventilation, extubated on postoperative day (POD)
1, and was transferred to a general ward on POD 3. The subsequent course
was uneventful, and the patient was discharged on POD 15.

\textbf{Discussion}

In our present case, the patient showed decreased cardiac function that
was thought to be caused by coronary artery stenosis, and hence great
attention was paid to the patient's hemodynamics during anesthesia
induction. Thus, it was necessary to select sedatives with minimal
circulatory depression during anesthesia induction to avoid circulatory
collapse. Careful determination of the dosage of the sedatives was also
required. The same applied to the administration of analgesics.
Recently, a short-acting benzodiazepine called remimazolam was approved
for use in Japan {[}1{]}. This drug has a shorter half-life than
midazolam, which is also a benzodiazepine, but has the advantage of a
faster onset of action and enables the evaluation of the presence or
absence of consciousness using electroencephalography {[}3,4{]}. Another
advantage of this drug is that it does not cause vascular pain, unlike
propofol {[}4{]}. Before the approval of remimazolam, total intravenous
anesthesia with propofol was commonly used for sedation during surgery.
However, propofol has a strong circulatory suppression effect {[}5{]},
which makes it difficult to use in patients with decreased cardiac
function, indicating a disadvantage. On the other hand, it has been
reported that remimazolam causes less circulatory depression, and its
use has enabled the maintenance of stable circulatory dynamics even in
patients with heart failure {[}6-8{]}. In our present case, circulatory
management was carried out using FloTrac to continuously monitor
variables, such as cardiac output and SVV, and both cardiac output and
SVV showed stable values without any events of circulatory failure. Our
present case indicates that the use of remimazolam is effective in the
anesthesia management of patients with decreased cardiac function
undergoing cardiac surgery. Furthermore, recent reports suggest that
compared to propofol, anesthesia management with remimazolam reduces the
surgical stress response and the effects of anesthetics on respiratory
function, and is superior in reducing anesthesia-associated side effects
{[}9{]}. In addition, remimazolam has been shown to potentially decrease
the incidence of postoperative delirium {[}10{]}, and its use is
believed to be effective for patients with respiratory abnormalities and
older patients at high risk of postoperative delirium.

\textbf{Conclusion}

Remimazolam is expected to become an option in the future for general
anesthesia in patients with decreased cardiac function.



\textbf{References}

{[}1{]} Keam SJ. Remimazolam: First Approval. Drugs. 2020
Apr;80(6):625-633. doi: 10.1007/s40265-020-01299-8. PMID: 32274703.

{[}2{]} Tan Y, Ouyang W, Tang Y, Fang N, Fang C, Quan C. Effect of
remimazolam tosilate on early cognitive function in elderly patients
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34907594; PMCID: PMC9303590.

{[}3{]} Shirozu K, Nobukuni K, Tsumura S, Imura K, Nakashima K, Takamori
S, Higashi M, Yamaura K. Neurological sedative indicators during general
anesthesia with remimazolam. J Anesth. 2022 Apr;36(2):194-200. doi:
10.1007/s00540-021-03030-7. Epub 2022 Jan 9. PMID: 34999964.

{[}4{]} Kim KM. Remimazolam: pharmacological characteristics and
clinical applications in anesthesiology. Anesth Pain Med (Seoul). 2022
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35139608; PMCID: PMC8841266.

{[}5{]} Sneyd JR, Absalom AR, Barends CRM, Jones JB. Hypotension during
propofol sedation for colonoscopy: a retrospective exploratory analysis
and meta-analysis. Br J Anaesth. 2022 Apr;128(4):610-622. doi:
10.1016/j.bja.2021.10.044. Epub 2021 Dec 13. PMID: 34916051; PMCID:
PMC9008870.

{[}6{]} Kim YY, Heo HJ, Lee JH, Cho HG, Kim G. Assessing the Safety of
Total Intravenous Anesthesia with Remimazolam in General Anesthesia for
Transcatheter Aortic Valve Implantation of Severe Aortic Valve Stenosis:
A Case Series. Medicina (Kaunas). 2022 Nov 19;58(11):1680. doi:
10.3390/medicina58111680. PMID: 36422219; PMCID: PMC9699221.

{[}7{]} Satoh T, Nishihara N, Sawashita Y, Ohno S, Hirata N, Yamakage M.
Remimazolam Anesthesia for MitraClip Implantation in a Patient with
Advanced Heart Failure. Case Rep Anesthesiol. 2021 May 5;2021:5536442.
doi: 10.1155/2021/5536442. PMID: 34035965; PMCID: PMC8116154.

{[}8{]} Furuta M, Ito H, Yamazaki M. Anaesthetic management using
remimazolam in a patient with severe aortic stenosis: a case report. BMC
Anesthesiol. 2021 Aug 14;21(1):202. doi: 10.1186/s12871-021-01422-6.
PMID: 34391395; PMCID: PMC8364063.

{[}9{]} Tang F, Yi JM, Gong HY, Lu ZY, Chen J, Fang B, Chen C, Liu ZY.
Remimazolam benzenesulfonate anesthesia effectiveness in cardiac surgery
patients under general anesthesia. World J Clin Cases. 2021 Dec
6;9(34):10595-10603. doi: 10.12998/wjcc.v9.i34.10595. PMID: 35004991;
PMCID: PMC8686148.

{[}10{]} Kaneko S, Morimoto T, Ichinomiya T, Murata H, Yoshitomi O, Hara
T. Effect of remimazolam on the incidence of delirium after
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10.1007/s00540-022-03148-2. Epub 2022 Dec 4. PMID: 36463532.

\textbf{List of abbreviations}

CABG: coronary artery bypass graft

CAG: coronary angiography

PSI: Patient State Index

SVV: stroke volume variation

CPB: cardiopulmonary bypass

POD: postoperative day

CHDF: continuous hemodiafiltration

\textbf{Declarations}

\textbf{Ethics approval and consent to participate}

Not applicable

\textbf{Consent for publication}

Written informed consent was obtained from the patient for publication
of this case report and the accompanying images.

\textbf{Availability of data and material}

Not applicable

\textbf{Competing interests}

The authors declare that they have no competing interests associated
with this manuscript.

\textbf{Funding}

None

\textbf{Authors' contributions}

YI and SN contributed to the anesthesia management of the patient,
conceptualization of the case report, and writing of the original draft.
SS contributed to the anesthesia management of the patient. SI and AK
edited the manuscript. MT was the overall supervisor of this case. All
authors read and approved the final manuscript.

\textbf{Acknowledgements}

The authors would like to thank H.A. Popiel for English language
editing.

\textbf{Authors' information}

\textbf{Affiliation}

Department of Anesthesiology

Tokyo Medical University Hospital

6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

Shingo Narumi, Yusuke Ishida, Sae Igarashi, Aya Kawachi, Shunya
Sekiguchi, and Mikiko Tomino



\textbf{Figure legends}

\textbf{Figure 1. Anesthetic record of the patient}

\textbf{Hosted file}

\verb`Figure.pptx`  available at \url{https://authorea.com/users/624673/articles/646928-anesthesia-using-remimazolam-during-coronary-artery-bypass-surgery-in-a-patient-with-decreased-left-ventricular-function}

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