\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,english]{babel}
\usepackage{CJKutf8}



\usepackage{float}








\begin{document}

\title{Perioperative management of a patient with von Recklinghausen's disease
who was expected to have difficulty in airway management: A case report}



\author[1]{Aiji Sato (Boku)}%
\author[1]{Izumi  Kuroda}%
\author[1]{Hideto Imura}%
\author[1]{Mayumi Hashimoto}%
\author[1]{Yoko Okumura}%
\author[1]{Naoko Tachi}%
\author[1]{Nagato Natsume}%
\author[1]{Masahiro Okuda}%
\affil[1]{Aichi Gakuin University School of Dentistry}%


\vspace{-1em}



  
  \date{May 28, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Von Recklinghausen's disease is characterized by skin pigmentation,
multiple neurofibromatosis, and osseous changes. In the management of
anesthesia, a variety of pathologies need to be taken into account. This
case describes the perioperative management of a patient with
Recklinghausen's disease suspected difficulty in airway management.%
\end{abstract}%



\sloppy


\textbf{Title:} Perioperative management of a patient with von
Recklinghausen's disease who was expected to have difficulty in airway
management: A case report

\textbf{Authors:} Aiji Sato (Boku) D.D.S., Ph.D.\textsuperscript{1},
Izumi Kuroda D.D.S. \textsuperscript{1}, Hideto Imura D.D.S.,
Ph.D.\textsuperscript{2}, Mayumi Hashimoto D.D.S.\textsuperscript{1},
Naoko Tachi D.D.S., Ph.D.\textsuperscript{1}, Yoko Okumura
D.D.S.\textsuperscript{1}, Nagato Natsume D.D.S.,
Ph.D.\textsuperscript{2}, Masahiro Okuda M.D., Ph.D.\textsuperscript{1}

\textbf{Institutional affiliations and address for each author}

\textsuperscript{1}Department of Anesthesiology, Aichi Gakuin University
School of Dentistry

\textsuperscript{2} Cleft lip and palate center, Aichi Gakuin University
Dental Hospital

\textbf{Corresponding author}

Aiji Sato (Boku), Department of Anesthesiology, Aichi Gakuin University
School of Dentistry 2-11 Suemori-dori, Chikusaku, Nagoya 464-8651, Japan

Tel: +81-52-759-2102, Fax; +81-52-759-2102, Email:
bokuaiji@dpc.aichi-gakuin.ac.jp

\textbf{Key Clinical Message}

In the anesthetic management of patients with von Willebrand's disease,
it is important to provide appropriate airway management, taking into
account the cutaneous laxity caused by neurofibromatosis of
Recklinghausen's disease.

\textbf{ABSTRACT}

Von Recklinghausen's disease is characterized by skin pigmentation,
multiple neurofibromatosis, and osseous changes. In the management of
anesthesia, a variety of pathologies need to be taken into account. This
case describes the perioperative management of a patient with
Recklinghausen's disease suspected difficulty in airway management.

\textbf{Keywords:} Von Recklinghausen's disease, Awake intubation,
Airway management

\textbf{Introduction}

Von Recklinghausen's disease, which was first reported by Friedrich
Daniel von Recklinghausen in 1882, is characterized by skin
pigmentation, multiple neurofibromatosis, and osseous
changes.\textsuperscript{1} The disease occurs in 1 out of 3000--4000
individuals.\textsuperscript{2} Problems in anesthesia management
include hypertension caused by renal artery stenosis and circulation
instability and major bleeding caused by
pheochromocytoma\textsuperscript{3--5}; airway obstruction caused by a
tumor in the mouth, pharynx, or airways \textsuperscript{6}; and an
aberrant response to muscle relaxants.\textsuperscript{7,8} Here, we
report the perioperative management of a patient with suspected
difficulty in airway management because of cutaneous laxity caused by
neurofibromatosis of Recklinghausen's disease and trismus resulting from
pathological fractures associated with mandibular osteomyelitis. The
patient provided written informed consent.

\textbf{Case Report}

A 74-year-old woman (height, 151 cm; weight, 58 kg) was scheduled for
tooth extraction and anti-inflammatory surgery under general anesthesia
for right mandibular osteomyelitis. She had been diagnosed with von
Recklinghausen's disease; her mother also had the same disease. Her past
medical history included surgery for appendicitis when she was 50 years
of age. Her preoperative examination findings, including blood tests,
chest radiography, electrocardiogram, and vital signs, were uneventful,
except for mild hypertension noted by an internist. In addition, airway
management was predicted to be difficult based on the following
preoperative airway findings: cutaneous laxity (Figure 1, left) and
mandibular micrognathia (Figure 1, right) caused by neurofibromatosis of
von Recklinghausen's disease and trismus resulting from pathological
fractures associated with mandibular osteomyelitis (Figure 2).

\textbf{Anesthetic Course}

Considering the airway findings, mask-to-face ventilation after
anesthesia induction was deemed inapplicable; therefore, we chose
fiberoptic intubation while maintaining spontaneous ventilation under
sedation. When the patient entered the operating room, standard monitors
were attached. No major problems were noted with her vital signs, except
for the systolic blood pressure of between 180 and 190. After
establishing an intravenous line in the left forearm and adequate
oxygenation at 6 L/min, we administered 2 mg of midazolam and 50 \selectlanguage{greek}µ\selectlanguage{english}g of
fentanyl. Once sedated, her systolic blood pressure decreased to
120--130. After confirming sufficient sedation and spontaneous
breathing, we performed cricothyroid cartilage puncture under ultrasound
guidance using 4\% xylocaine. After puncture, awake intubation was
performed using a fiberscope from the right nasal cavity. The intubation
was successful. Thereafter, anesthesia was induced with 50 mg of
propofol and 40 mg of rocuronium. Intraoperatively, anesthesia was
maintained using oxygen, air, desflurane, fentanyl, and remifentanil.
Postoperatively, the patient recovered from the muscle relaxants, as
confirmed by neuromuscular monitoring. Then, 150 mg of sugammadex, a
rocuronium antagonist, was administered. After body movement, eye
opening, adequate spontaneous breathing, and obedience were confirmed,
she was extubated. Subsequently, the systolic blood pressure increased
to 180--190. Other vital signs remained within the normal range. The
operation lasted for 1 hour and 4 minutes, with 2 hours and 12 minutes
of anesthesia. The amount of blood loss was 30 g.

\textbf{Discussion}

As described above, various problems are associated with anesthesia
management in patients with von Recklinghausen's disease. In the present
case, the worst problem in anesthesia management was the difficulty in
establishing an intact airway. Generally, mask-to-face ventilation is
difficult or impossible in patients with upper-airway deformity because
of several factors, including tumor, abscess, radiation history, and
surgery history\textsuperscript{9,10}; thus, awake intubation is often
indicated. Although awake intubation is safe because it is performed
while maintaining the patient's spontaneous breathing, it must be chosen
after careful consideration because it can be painful if the
anestesiologist is not skilled. The procedure cannot be performed
without patient cooperation. In addition, persistent airway injuries
have been reported.\textsuperscript{11} In a previous case report, a
patient with airway difficulty was anesthetized using remimazolam, which
has become clinically available recently in Japan, but was later
awakened because mask-to-face ventilation was
impossible.\textsuperscript{12} In our case, mask-to-face ventilation
was also impossible because of cutaneous laxity caused by
neurofibromatosis, which is a characteristic of von Recklinghausen's
disease. Therefore, we had to choose awake intubation. The use of
midazolam, fentanyl, and a local anesthetic agent to reduce the
patient's pain allowed an uneventful awake intubation. As a
precautionary measure, a tube is inserted from the nasal cavity. The
tube's tip is placed close to the glottis, serving as an airway if
oxygenation is reduced due to insufficient spontaneous ventilation
during tracheostomy under sedation. Fortunately, such a tube was not
needed in the present case. A sedative agent with minimal respiratory
depression, such as dexmedetomidine, may be a better choice when the
impossibility of mask-to-face ventilation is suspected.

Another problem we encountered during anesthesia management was the
increase in systolic blood pressure, which is similar to a previous
report.\textsuperscript{13} Previous reports have documented cases of
massive bleeding caused by blood vessel fragility, which is a
characteristic of von Willebrand disease, in addition to difficulty in
intraoperative blood pressure management.\textsuperscript{13} In our
case, the systolic blood pressure was elevated to 180--190 owing to
tension upon entering the operating room and stimulation during
extubation. Thus, the possibility that the patient had hypertension
concomitantly cannot be ruled out. The patient's blood pressure was
slightly high before the operation, which was noted by an internist.
Therefore, preoperative interventions, such as the administration of
antihypertensive medication, should have been performed. Although no
major circulatory changes were noted intraoperatively, adequate
consideration of the circulatory system may be necessary even if the
patient did not report any problems.

Furthermore, the effects of muscle relaxants persist in some cases. In
our case, the muscle relaxant effect subsided although it was monitored
continuously by neuromuscular monitoring during the operation. To ensure
safety, we reversed the muscle relaxant before awakening the patient
from anesthesia. In the case we experienced, there was no residual
muscle relaxant, but since the tracheal intubation was performed under
conscious intubation without muscle relaxants, it may not have been
necessary to use muscle relaxants intraoperatively and risk their
prolongation.

\textbf{Conclusion}

We experienced the perioperative management of a patient with suspected
difficulty in airway management because of cutaneous laxity caused by
neurofibromatosis of Recklinghausen's disease and trismus resulting from
pathological fractures associated with mandibular osteomyelitis.
Although we were able to secure the airway by conscious intubation
without any problems, there were some points to be considered regarding
intercirculatory management and the use of muscle relaxants.

\textbf{Acknowledgements}

Not applicable

\textbf{Funding}

None

\textbf{Conflict of interest}

The authors declare that we have no conflict of interest.

\textbf{Data availability statement}

Not applicable due to patient privacy concerns.

\textbf{Author's contributions}

All authors contributed to the case. Preoperative management and
anesthetic planning were performed by AS, IK, YO, MH and NT. Anesthetic
Management was performed by AS and IK. The Operation was performed by
HI. The first draft of the manuscript was written by AS and all authors
commented on previous versions of the manuscript. NN and MO helped with
the supervision of the manuscript and development of the overall
periopertative plan. All authors read and approved the final manscript.

\textbf{Ethical approval}

Not applicable.

\textbf{Consent for publication}

The authors obtained written consent for publication from the patient.

\textbf{ORCID} Aiji Sato (Boku) 0000-0003-0182-2543

\textbf{References}

Von Recklinghausen FD. Ueber die multiplen Fibrome der Haut und ihre
Beziehung zu den multiple Neuromen. Berlin: Hirschwald; 1882.

Niimura M. Overview and clinical aspects of neurofibromatosis 1. Gann
Monograph on Cancer Reserch. 1999; 46: 115-126.

3)\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}Cho T, Fukushige T, Taze C, et al. An experience of anesthesia of
Recklinghausen disease leading to massive hemorrhage. J Clin Anes
(Japan). 1987; 11:62-64. (Article in Japanese)

4) Steen TR. Hypertension during operation due to unsuspected
pheochromocytoma associated with neurofibromatosis. Anaesthesia. 1957;
2: 80.

5) Nishiyama T, Odaka Y, Akao M, et al. Experience in anesthesia of
mediastinal tumor excision in a patient with Recklinghausen disease. J
Clin Anes (Japan). 1990; 14: 427-428. (Article in Japanese)

6) Tominaga S, Shiraishi T, Akiyama Y, et al. A case of general
anesthesia for a patient with von Recklinghausen syndrome and tumors of
the oral cavity. J\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}Jpn Dent\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}Soc\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}Anesthesiol. 1988; 16: 305-308.
(Article in Japanese)

7) Magbagbeola JA. Abnormal responses to muscle relaxants in a patient
with Von Recklinghausen's disease (multiple neurofibromatosis). Br J
Anaesth. 1970; 42: 710.

8) Manser J. Abnormal responses in von Recklinghausen's disease. Br J
Anaesth. 1970;

42: 183.

9) Kheterpal S,~Martin L, Shanks AM, et al. Prediction and outcomes of
impossible mask ventilation: a review of 50,000 anesthetics.
Anesthesiology. 2009; 110: 891-897.

El-Orbany M,~Woehlck HJ. Difficult mask ventilation. Aesth Analg, 2009;
109: 1870-1880.

Maktabi MA, Hoffman H, Funk G, et al. Laryngeal trauma during awake

fiberoptic intubation. Anesth Analg. 2002; 95: 1112-1114.

Sato A, Hashimoto M, Tachi N, et al. Experience with remimazolam in two
cases in which difficult airway management was predicted. J Clin Anes
(Japan). 2021; 45: 1346-1348. (Article in Japanese)

Tanigawa H, Oomizo H, Naito M, et al. Anesthesia experience in a case of
von Reclinghausen\textsuperscript{,}s deisease in when the operation had
to be concluded prematurely. J\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}Jpn Dent\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}Soc\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}Anesthesiol. 1997; 25:
251-255. (Article in Japanese)

\textbf{Figure Legends}

Figure1

Cutaneous laxity (left) and mandibular micrognathia (right) caused by
neurofibromatosis of von Recklinghausen's disease

Figure2

Pathological fractures associated with mandibular osteomyelitis\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure1/Figure1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure2/Figure2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

