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\begin{document}

\title{Negative pressure pulmonary edema due to upper airway obstruction after
general anesthesia in a patient with Parkinson's disease: a case report}



\author[1]{Ayaka Hasegawa}%
\author[1]{Naoko Niimi}%
\author[1]{Chieko Mitaka}%
\author[1]{Masakazu Hayashida}%
\affil[1]{Juntendo University}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\selectlanguage{english}
\begin{abstract}
A 65-year-old man with Parkinson's disease (PD) underwent spine surgery
under general anesthesia, 13 hours after the last medication for PD.
Postoperatively, negative pressure pulmonary edema developed following
upper airway obstruction, a possible complication of PD. Oxygenation
improved with high-flow nasal cannula therapy. Continued medication
might have prevented such complications.%
\end{abstract}%



\sloppy


Negative pressure pulmonary edema due to upper airway obstruction after
general anesthesia in a patient with Parkinson's disease: a case report

Ayaka Hasegawa\textsuperscript{1*}, Naoko Niimi\textsuperscript{1},
Chieko Mitaka\textsuperscript{1}, Masakazu Hayashida\textsuperscript{1}

\textsuperscript{1}Department of Anesthesiology and Pain Medicine,
Juntendo University Faculty of Medicine

*Corresponding author: Ayaka Hasegawa

E-mail address: a.hasegawa.if@juntendo.ac.jp

Department of Anesthesiology and Pain Medicine, Juntendo University
Faculty of Medicine,

3-1-3, Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan

Phone: +81-3-3813-3111

Fax: +81-3-3811-7285

Coauthor e-mail addresses

Naoko Niimi:\emph{n-niimi@juntendo.ac.jp}

Chieko Mitaka: c-mitaka@juntendo.ac.jp

Masakazu Hayashida:\emph{mhaya@juntendo.ac.jp}

\textbf{Abstract}

A 65-year-old man with Parkinson's disease (PD) underwent spine surgery
under general anesthesia, 13 hours after the last medication for PD.
Postoperatively, negative pressure pulmonary edema developed following
upper airway obstruction, a possible complication of PD. Oxygenation
improved with high-flow nasal cannula therapy. Continued medication
might have prevented such complications.

\textbf{Keywords}

negative pressure pulmonary edema, Parkinson's disease, upper airway
obstruction



\textbf{Background}

Parkinson's disease (PD) is a common disorder that is complicated by
multiple respiratory abnormalities, including upper airway obstruction
(UAO).\textsuperscript{1} To our knowledge, negative pressure pulmonary
edema (NPPE), a noncardiogenic pulmonary edema induced by the generation
of high negative intrathoracic pressure needed to overcome
UAO,\textsuperscript{2} has not been reported in patients with PD. We
report the first case of NPPE after general anesthesia in a patient with
PD.

\textbf{Case presentation}

A 65-year-old man (175.0 cm, 65.0 kg) with a 23-year history of PD was
scheduled to undergo C3-C7 cervical laminectomy with C3/C4 posterior
fixation for cervical spondylosis. The patient was taking antiparkinson
drugs, including levodopa-carbidopa taken four times a day. Symptoms of
PD were well-controlled with drugs so that he was able to live
independently. He was admitted to the hospital the day before surgery.
The patient took the last medication the night before surgery, 13 hours
before anesthesia. Considering the well-controlled PD status, oral
anitparkinson drugs on the morning of surgery were neither administrated
nor replaced by intravenous levodopa.

General anesthesia was induced and maintained with continuous infusions
of propofol and remifentanil. Rocuronium (40 mg) was given to facilitate
tracheal intubation. After the patient was placed in the prone position,
neuromuscular relaxation was antagonized with sugammadex (150 mg) for
monitoring of motor-evoked potentials, which remained unsuppressed
throughout surgery. Arterial oxygen saturation (SpO\textsubscript{2})
was maintained between 97\% and 99\%, and arterial oxygen tension
(PaO\textsubscript{2}) was 201 mmHg with inspired oxygen fraction
(F\textsubscript{I}O\textsubscript{2}) of 0.5. Fentanyl (150 \selectlanguage{greek}μ\selectlanguage{english}g) and
acetaminophen (1,000 mg) were intravenously administrated for immediate
postoperative analgesia. Durations of surgery and anesthesia were 161
and 254 minutes, respectively. Intraoperative fluid infusion, blood
loss, and urine output were 1,410 mL, 60 mL, and 400 mL, respectively.

After emergence from anesthesia, a sufficient tidal volume and
respiratory rate were confirmed. The patient could take a deep breath
and move extremities voluntarily, as requested by anesthesiologists.
Immediately after tracheal extubation, however, the patient presented
with labored breathing. Inspiratory stridor was heard. Systolic blood
pressure increased to 200 mmHg. SpO\textsubscript{2} dropped to 78\%.
PaO\textsubscript{2} was 61 mmHg during administration of oxygen at
8L/min via face mask. The patient's UAO was immediately treated with a
jaw thrust maneuver and tightly fitted face mask. An immediate chest
X-ray showed diffuse bilateral pulmonary consolidation without an
increased cardiothoracic ratio, consistent with negative pressure
pulmonary edema (NPPE) (Figure 1). Thus, 10-cm H\textsubscript{2}O
positive end-expiratory pressure (PEEP) was applied to the spontaneously
breathing patient using an anesthesia circuit.
PaO\textsubscript{2}increased to 105 mmHg.

The patient was transferred to the intensive care unit. High-flow nasal
cannula therapy (HFNC) was initiated with
F\textsubscript{I}O\textsubscript{2} of 0.6 and a flow rate of 50 L/min.
NPPE improved by the morning of postoperative day (POD) 1;
PaO\textsubscript{2} increased to 204 mmHg with FiO\textsubscript{2}0.6.
Administration of antiparkinson drugs was resumed. On POD 2, the patient
was weaned from HFNC, and returned to the ward without any oxygen
supply.

\textbf{Discussion}

Although UAO can develop as a manifestation of PD,\textsuperscript{1} it
seemed necessary to rule out other causes of UAO in this patient. First,
anesthesia- or opioid-related respiratory depression or UAO was unlikely
because the patient showed adequate respiration, alertness, and
responsiveness before extubation. Second, UAO due to alterations in the
upper airway anatomy caused by cervical spine surgery\textsuperscript{3}
was unlikely because of no finding of upper airway stenosis on cervical
spine X-rays taken before extuabation. Therefore, it was likely that UAO
developed as a manifestation of PD.\textsuperscript{1}

The patient had taken the last antiparkinson drugs 13 hours before
anesthesia. The withdrawal of drugs might be long enough to diminish
their effects, thereby causing UAO. Reportedly, duration of action of
levodopa-carbidopa to reduce motor disability lasts as short as 3 to 6
hours.\textsuperscript{4, 5} After a 12-hour withdrawal of antiparkinson
drugs, a significant change in the spirometry indicative of UAO occurs
in a substantial number of PD patients,\textsuperscript{6, 7} which is
reversed by levodopa.\textsuperscript{6} Especially, PD patients
exhibiting laryngopharyngeal motor dysfunction, indicated mainly by
hypophonia, after a 12-hour drug withdrawal have a threefold greater
chance of presenting with obstructive sleep apnea (OSA) unrelated to
obesity, neck circumference, or the Mallampati score, compared with
those without such dysfunction.\textsuperscript{7} Episodes of severe
UAO that were successfully reversed by antiparkinson drugs, including
levodopa, have been reported.\textsuperscript{8-10} These data suggest
that in our patient, daily antiparkinson drugs should have been
continued perioperatively or replaced by intravenous levodopa to
minimize the risk of developing UAO and subsequent NPPE.

In our patient, UAO and NPPE improved with HFNC without a resumption of
antiparkinson drugs. HFNC is able to deliver a consistent oxygen supply
to the alveoli by constantly applying positive pressure, enabling the
patient to maintain a high level of oxygen
supply.\textsuperscript{11}Further, generation of PEEP helps in
reduction of anatomical dead space, carbon dioxide washout, recruitment
of collapsed alveoli, and ultimate improvement in
oxygenation.\textsuperscript{11} Through such effects, HFNC improves
pulmonary edema.\textsuperscript{11} In addition, HFNC improves UAO in
patients with OSA.\textsuperscript{12} Therefore, our experience also
suggests that HFNC is effective in improving UAO and subsequent NPPE in
patients with PD.

\textbf{Conclusion}

We experienced upper airway obstruction and negative pressure pulmonary
edema that developed immediately after anesthesia and extubation in a
patient with Parkinson's disease. Our experience suggests that in
patients with Parkinson's disease, antiparkinson drugs should be
continued perioperatively to minimize risks of such complications, and
high-flow nasal cannula therapy improves upper airway obstruction and
negative pressure pulmonary edema.

\textbf{List of abbreviations}

FiO\textsubscript{2}, inspired oxygen fraction; HFNC, high-flow nasal
cannula therapy; NPPE, negative pressure pulmonary edema; OSA,
obstructive sleep apnea; PaO\textsubscript{2}, arterial oxygen tension;
PD, Parkinson's disease; PEEP, positive end-expiratory pressure;
SpO\textsubscript{2}, arterial oxygen saturation; UAO, upper airway
obstruction

\textbf{Consent for publication}

Written informed consent was obtained from the patients for publication
of this case report and any accompanying images. A copy of the written
consent is available for review by the Editor-in-Chief of this journal.

\textbf{Competing interests}

The authors declare that they have no competing interests.

\textbf{Funding}

None

\textbf{Authors' contributions}

AH was a major contributor to manuscript writing. AH and NN were
responsible for patient care and data collection. CM and MH contributed
to data interpretation.

All authors read and approved the final manuscript.

\textbf{Figure legend}

Figure 1.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Brown LK. Respiratory dysfunction in Parkinson's disease. Clin Chest
  Med.~1994;15:715-27.
\item
  Lemyze M, Mallat J. Understanding negative pressure pulmonary edema.
  Intensive Care Med 2014;40:1140-1143. doi 10.1007//s00134-014-3307-7.
\item
  Tagaya T, Akeda K, Asanuma Y, Miyabe M, Arisaka H, Furuya, H, Yoshida
  K, Sakuraba S. Upper airway obstruction associated with flexed
  cervical position after posterior occipitocervical fusion. J
  Anesth.~2011;25:120-2. doi: 10.1007/s00540-010-1069-0.
\item
  Senek M, Aquilonius S, Askmark H, Bergquist F, Constantinescu R,
  Ericsson A, Lycke S, Medvedev A, Memedi M, Ohlsson F, Spira J, Westin
  J, Nyholm D. Levodopa/carbidopa microtablets in Parkinson's disease: a
  study of pharmacokinetics and blinded motor assessment. Eur J Clin
  Pharmacol.~2017;73:563-571.~doi: 10.1007/s00228-017-2196-4.
\item
  Hauser RA, Ellenbogen A, Khanna S, Gupta S, Modi NB. Onset and
  duration of effect of extended-release carbidopa-levodopa in advanced
  Parkinson's disease. Neuropsychiatr Dis Treat.~2018;14:839-845.~doi:
  10.2147/NDT.S153321.
\item
  Herer B, Arnulf I, Housset B. Effects of levodopa on pulmonary
  function in Parkinson's disease. Chest.~2001;119:387-93.~doi:
  10.1378/chest.119.2.387.
\item
  Bahia CMCS, Pereira JS, Lopes AJ. Laryngopharyngeal motor dysfunction
  and obstructive sleep apnea in Parkinson's disease. Sleep Breath.
  2019;23:543-550. doi: 10.1007/s11325-018-1729-0.
\item
  Vincken WG, Darauay CM, Cosio MG. Reversibility of upper airway
  obstruction after levodopa therapy in Parkinson's disease. Chest.
  1989; 96(1):210-2. doi: 10.1378/chest.96.1.210.
\item
  Lydon AM, Boylan JF. Reversibility of parkinsonism-induced acute upper
  airway obstruction by benztropine therapy. Anesth Analg. 1998;
  87:975-6. doi: 10.1097/00000539-199810000-00043.
\item
  Tsai CC, Wu MN, Wu MN, Liou LM, Chang YP. Levodopa reverse stridor and
  prevent subsequent endotracheal intubation in Parkinson disease
  patients with bilateral vocal cord palsy: A case report. Medicine
  (Baltimore).~2016;95:e5559.~doi: 10.1097/MD.0000000000005559.
\item
  Adhikari P, Bhattarai S, Gupta A, Ali E, Ali M, Riad M, Mostafa JA.
  Physiological Effects of High-Flow Nasal Cannula Therapy and Its Use
  in Acute Cardiogenic Pulmonary Edema. Cureus.~2021;13:e13372.~doi:
  10.7759/cureus.13372.
\item
  Yan H, Qinghua L, Mengyuan P, Yaoyu C, Long Z, Mengjie L, Xiaosong D,
  Fang H. High flow nasal cannula therapy for obstructive sleep apnea in
  adults. Sleep Breath.~2022 Jun;26(2):783-791.~doi:
  10.1007/s11325-021-02453-6.
\end{enumerate}\selectlanguage{english}
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