CORRESPONDENCE
volume of ,110 ml to identify patients at greatest risk of PES.
Methodological differences in the performance of a CLT include what
predetermined cutoff value is used to define test failure and whether an
absolute or relative (to the VT) value is used. Although significant
variation exists, an absolute volume of ,110 ml has been used most
consistently in the literature (1) and thus was chosen here. Furthermore,
as acknowledged by Girard and colleagues, performing a CLT on all
patients before extubation has not been shown to improve clinical
outcomes, and significantly delays liberation (2). For this reason, the
proposed protocol targets high-risk patients.
Historically, studies that used corticosteroids for PES
indicated a lack of efficacy; however, most used a single dose of the
study drug administered just 1 hour before extubation (3). Likely,
these studies were limited by the pharmacodynamic profile of
corticosteroids, resulting in a delayed onset of action. More
recent literature suggests that multiple doses of corticosteroid
administered 4–48 hours before extubation are effective in
decreasing the rate of PES and the need for reintubation (4, 5).
Because of the high specificity and variable sensitivity of the CLT,
pharmacoprophylaxis to prevent PES was incorporated into the
protocol for patients who fail the CLT, but CLT failure does
not preclude extubation (1). After notification of the attending
physician, 20 mg of methylprednisolone is administered
intravenously every 4 hours for four doses, with extubation
attempted immediately after the last dose. This regimen was
chosen because of its use in a vastly larger study population compared
with other corticosteroid regimens (4).
Treatment of PES is regrettably omitted from the recent
guidelines, likely owing to the dearth of clinical literature, but it may
provide a benefit in preventing reintubation. We propose treatment of
PES with methylprednisolone and racemic epinephrine. Wittekamp
and colleagues previously used 0.5 mg/kg of prednisolone
once (approximately 0.4 mg/kg methylprednisolone) and have since
recommended 20–40 mg of methylprednisolone continued for
24–48 hours (1, 6). We chose to use 40 mg of methylprednisolone
administered intravenously once to avoid weight-based dosing and
as an escalation in therapy from the prophylaxis dose.
Post-extubation laryngeal edema and PES pose relatively
common obstacles to ventilator liberation, but they are also
highly manageable. Clinical practice guidelines have provided
important recommendations for preventing PES. We propose the
optimization of these recommendations through institution-based
protocolization. n
Author disclosures are available with the text of this letter at
www.atsjournals.org.
Susan E. Smith, Pharm.D.
University of Georgia College of Pharmacy
Athens, Georgia
and
Piedmont Athens Regional Medical Center
Athens, Georgia
Andrea S. Newsome, Pharm.D.
University of Georgia College of Pharmacy
Augusta, Georgia
and
Augusta University Medical Center
Augusta, Georgia
Correspondence
W. Anthony Hawkins, Pharm.D.
University of Georgia College of Pharmacy
Albany, Georgia
and
Medical College of Georgia at Augusta University
Albany, Georgia
ORCID ID: 0000-0002-5171-8405 (S.E.S.).
References
1. Pluijms WA, van Mook WN, Wittekamp BH, Bergmans DC.
Postextubation laryngeal edema and stridor resulting in respiratory
failure in critically ill adult patients: updated review. Crit Care 2015;19:
295.
2. Girard TD, Alhazzani W, Kress JP, Ouellette DR, Schmidt GA,
Truwit JD, et al.; ATS/CHEST Ad Hoc Committee on Liberation from
Mechanical Ventilation in Adults. An Official American Thoracic
Society/American College of Chest Physicians clinical practice
guideline. Liberation from mechanical ventilation in critically ill
adults: rehabilitation protocols, ventilator liberation protocols,
and cuff leak tests. Am J Respir Crit Care Med 2017;195:
120–133.
3. Darmon JY, Rauss A, Dreyfuss D, Bleichner G, Elkharrat D, Schlemmer B,
et al. Evaluation of risk factors for laryngeal edema after tracheal
extubation in adults and its prevention by dexamethasone. A placebo-
controlled, double-blind, multicenter study. Anesthesiology 1992;77:
245–251.
4. François B, Bellissant E, Gissot V, Desachy A, Normand S, Boulain T,
et al.; Association des Réanimateurs du Centre-Ouest (ARCO). 12-h
pretreatment with methylprednisolone versus placebo for prevention
of postextubation laryngeal oedema: a randomised double-blind trial.
Lancet 2007;369:1083–1089.
5. Cheng KC, Chen CM, Tan CK, Chen HM, Lu CL, Zhang H.
Methylprednisolone reduces the rates of postextubation
stridor and reintubation associated with attenuated cytokine
responses in critically ill patients. Minerva Anestesiol 2011;77:
503–509.
6. Wittekamp BH, van Mook WN, Tjan DH, Zwaveling JH, Bergmans DC.
Clinical review: post-extubation laryngeal edema and extubation
failure in critically ill adult patients. Crit Care 2009;13:233.
Copyright © 2018 by the American Thoracic Society
Reply to Smith et al.
From the Authors:
We appreciate the letter from Smith and colleagues regarding
treatment recommendations for post-extubation stridor (PES).
When we determined the scope and topics of this guideline, we
focused on six pertinent clinical questions regarding liberation from
mechanical ventilation. Whether to use the cuff leak test to identify
patients at high risk for PES was one of these questions, but how
to treat PES when it occurs, although important, was not a question
we addressed in this guideline (1). With the exception of post-
extubation preventive noninvasive ventilation, our guideline
focused on pre-extubation interventions that may speed liberation
from mechanical ventilation. Our focus on the cuff leak test,
however, led us to also discuss prevention of PES with corticosteroids,
Originally Published in Press as DOI: 10.1164/rccm.201712-2600LE on
January 16, 2018
1505

and we recognize that clinicians are eager for guidance regarding
treatment when extubation is followed by stridor.
Based on the existing literature on this topic, including the
articles cited in the letter, we would not have been able to make
a recommendation on treatment of PES (2, 3). Although it is
commonly used in practice, and with a seemingly sound basis,
treatment with corticosteroids or nebulized epinephrine has
not been proven to be effective, and the optimal dosing (if it is
effective) has not been determined. In pediatric subjects,
neither the extent nor the time to development of post-
extubation upper-airway obstruction was altered in a 2 3 2
factorial design study of intravenous corticosteroids/isotonic
saline every 6 hours 3 4 doses and nebulized epinephrine/isotonic
saline every 4 hours 3 6 doses (4). Of note, nebulized epinephrine
has been shown to be effective in children with viral croup, but
even for that indication, the optimal dosing has not been
established (5).
In addition to a PES treatment regimen, the authors also
suggest a corticosteroid dose and frequency for patients with an
inadequate cuff leak. Because the studies that addressed prevention
of PES applied different doses and dosing schedules (6–9), and it is
unclear whether one is superior to another, we chose to be silent on
the dosing regimens.
We agree with Smith and colleagues that the risk involved
in administering inhaled epinephrine and a single dose of
corticosteroids is probably low. However, sufficient evidence
regarding both the effectiveness and optimal dosing for corticosteroids
and inhaled epinephrine is lacking. High-quality evidence
from clinical trials is needed to inform future clinical practice
guidelines. n
Author disclosures are available with the text of this letter at
www.atsjournals.org.
Jonathon D. Truwit, M.D.
Froedtert and Medical College of Wisconsin
Milwaukee, Wisconsin
Timothy D. Girard, M.D.
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
Waleed Alhazzani, M.B. B.S., M.Sc.
McMaster University
Hamilton, Ontario, Canada
John P. Kress, M.D.
University of Chicago
Chicago, Illinois
Daniel R. Ouellette, M.D.
Henry Ford Hospital
Detroit, Michigan
Gregory A. Schmidt, M.D.
University of Iowa
Iowa City, Iowa
Peter E. Morris, M.D.
University of Kentucky
Lexington, Kentucky
ORCID IDs: 0000-0001-7129-9300 (J.D.T.); 0000-0002-9833-4871 (T.D.G.).
1506 American Journal of Respiratory and Critical Care Medicine Volume 197 Number 11 | June 1 2018
CORRESPONDENCE
References
1. Girard TD, Alhazzani W, Kress JP, Ouellette DR, Schmidt GA, Truwit JD,
et al.; ATS/CHEST Ad Hoc Committee on Liberation from Mechanical
Ventilation in Adults. An Official American Thoracic Society/American
College of Chest Physicians clinical practice guideline. Liberation from
mechanical ventilation in critically ill adults: rehabilitation protocols,
ventilator liberation protocols, and cuff leak tests. Am J Respir Crit
Care Med 2017;195:120–133.
2. Pluijms WA, van Mook WN, Wittekamp BH, Bergmans DC. Postextubation
laryngeal edema and stridor resulting in respiratory failure in critically ill
adult patients: updated review. Crit Care 2015;19:295.
3. Wittekamp BH, van Mook WN, Tjan DH, Zwaveling JH, Bergmans DC.
Clinical review: post-extubation laryngeal edema and extubation
failure in critically ill adult patients. Crit Care 2009;13:233.
4. Cesar RG, de Carvalho WB. L-epinephrine and dexamethasone in
postextubation airway obstruction: a prospective, randomized, double-blind
placebo-controlled study. Int J Pediatr Otorhinolaryngol 2009;73:1639–1643.
5. Bjornson C, Russell K, Vandermeer B, Klassen TP, Johnson DW.
Nebulized epinephrine for croup in children. Cochrane Database Syst
Rev 2013;(10):CD006619.
6. Cheng KC, Chen CM, Tan CK, Chen HM, Lu CL, Zhang H. Methylprednisolone
reduces the rates of postextubation stridor and reintubation
associated with attenuated cytokine responses in critically ill patients.
Minerva Anestesiol 2011;77:503–509.
7. Cheng KC, Hou CC, Huang HC, Lin SC, Zhang H. Intravenous injection
of methylprednisolone reduces the incidence of postextubation stridor
in intensive care unit patients. Crit Care Med 2006;34:1345–1350.
8. Lee CH, Peng MJ, Wu CL. Dexamethasone to prevent postextubation
airway obstruction in adults: a prospective, randomized, double-blind,
placebo-controlled study. Crit Care 2007;11:R72.
9. Wang CL, Tsai YH, Huang CC, Wu YK, Ye MZ, Chou HM, et al. The role
of the cuff leak test in predicting the effects of corticosteroid treatment
on postextubation stridor. Chang Gung Med J 2007;30:53–61.
Copyright © 2018 by the American Thoracic Society
Treatment of Pulmonary Lymphangioleiomyomatosis
during Pregnancy
To the Editor:
We read the clinical practice guidelines for lymphangioleiomyomatosis
(LAM) with great interest, and we appreciate the useful messages for
the diagnosis and management of the disease (1, 2). These messages
seemed reasonable, with great care taken in treating premenopausal
women of childbearing age. Therefore, I will comment on the
question, How on earth should we treat patients with LAM who
still long for pregnancy? Pregnant women with LAM are known
to have an increased risk for complications, such as pneumothorax,
chylous effusion, and possible bleeding from renal angiomyolipomas
(3). In the past, the risk for such complications during the pregnancy
has been overrepresented because of the potential risk resulting from
estrogens in the pathogenesis of LAM. However, a recent retrospective
study has suggested that pregnancy might not significantly contribute
to the acceleration of the disease (4). Therefore, some women with
LAM might tolerate pregnancy only if the disease is mild and lung
function is relatively preserved and does not decline progressively. In
such cases, the use of drugs during the pregnancy and the perinatal
period is an important consideration. Rapamycin (an inhibitor of
Originally Published in Press as DOI: 10.1164/rccm.201712-2566LE on
January 22, 2018