Download Severe status asthmaticus

Severe status asthmaticus: Management with permissive
hypercapnia and inhalation anesthesia
Gökhan M. Mutlu, MD; Phillip Factor, DO, FCCP; David E. Schwartz, MD, FCCP;
Jacob I. Sznajder, MD, FCCP
Objective: To describe the difficulties that can be encountered
during mechanical ventilation of severe status asthmaticus and to
discuss the safety of permissive hypercapnia as a ventilatory
strategy and the role and limitations of inhalation anesthesia in
the treatment of refractory cases.
Design: Case series and review of literature.
Setting: Intensive care unit of a tertiary care hospital.
Patients: Two patients with severe status asthmaticus.
Interventions: Administration of inhalational anesthetics.
Measurements and Main Results: Both patients had respiratory
failure secondary to status asthmaticus requiring mechanical
ventilation and permissive hypercapnia. They also received inhalational anesthetics because of refractory bronchoconstriction.
Levels of PaCO2 in each case were among the highest and most
prolonged elevations (>150 mm Hg for several hours) reported to
M
anagement of status asthmaticus includes the administration of bronchodilators, corticosteroids, and,
in very severe, refractory cases, mechanical ventilation. Concerns that the risks
of high end-inspiratory pressures and attendant barotrauma and volutrauma exceed the benefits of normalization of arterial blood gases have shifted the aim of
therapy from normalizing arterial blood
gases to protecting the lungs and tolerating elevated levels of arterial CO2. This
“permissive hypercapnia” has increasingly been accepted as a strategy to prevent complications associated with severely elevated lung volumes and
From Pulmonary and Critical Care Medicine, Evanston Northwestern Healthcare, Evanston, IL (GMM, PF);
Pulmonary and Critical Care Medicine, Northwestern
University Medical School, Chicago, IL (GMM, PF, JIS);
and the Department of Anesthesiology, University of
Illinois at Chicago, and Michael Reese Hospital, Chicago, IL (DES).
Address request for reprints to: Jacob I. Sznajder, MD, Division of Pulmonary and Critical Care
Medicine, Northwestern University, 300 East Superior, Tarry 14-707, Chicago, IL 60611. E-mail:
[email protected]
Copyright © 2002 by Lippincott Williams & Wilkins
Crit Care Med 2002 Vol. 30, No. 2
date. In one case, life-threatening difficulties with ventilation
were encountered related to the use of an anesthesia ventilator.
Although they had complications related to the severity of their
illnesses, both were treated to recovery.
Conclusions: Mechanical ventilation in severe status asthmaticus
can be challenging. Permissive hypercapnia is a relatively safe strategy in the ventilatory management of asthma. High levels of hypercapnia and associated severe acidosis are well tolerated in the
absence of contraindications (i.e., preexisting intracranial hypertension). Inhalation anesthesia may be useful in the treatment of refractory cases of asthma but should be used carefully because it may be
hazardous owing to poor flow capabilities of most anesthesia ventilators. (Crit Care Med 2002; 30:477–480)
KEY WORDS: status asthmaticus; mechanical ventilation; complications; inhalational anesthetics; permissive hypercapnia
dynamic hyperinflation (1). Although it is
widely practiced, there is no consensus
on the level of hypercapnia that is considered safe. “How permissive can we be?”
remains an unanswered question.
We report two patients with severe
status asthmaticus treated with mechanical ventilation and permissive hypercapnia, who also received inhalational anesthetics. Each case is among the highest
and most prolonged elevations in PaCO2
in the literature. Both patients had significant complications but were treated
to complete recovery. Difficulties during
mechanical ventilation, permissive hypercapnia, and the use of anesthesia ventilators to deliver inhalational anesthetics
can be a challenge to the treatment of
very severe asthma.
CASE 1
A 24-yr-old woman with a history of
mild, persistent asthma came to the
emergency department with complaints
of shortness of breath and wheezing of 1
day’s duration. She had never been hospitalized for asthma and had been treated
only with albuterol. In the emergency
department, she was noted to be in severe
respiratory distress and was orotracheally
intubated. She subsequently received intravenous corticosteroids and albuterol
via continuous nebulization. Because of
severe bronchoconstriction and high
peak airway pressures, she was sedated
with midazolam, paralyzed with vecuronium, and admitted to the intensive care
unit (ICU). Physical exam upon arrival to
the ICU revealed limited air movement
and subcutaneous emphysema around
the neck and upper chest. Initial ventilator settings on a Puritan-Bennett 7200
ventilator (Mallinckrodt, Hazelwood, MO)
were assist-control, rate of 12/minute,
tidal volume of 500 mL (8 mL/kg of total
body weight), and positive end-expiratory
pressure (PEEP) of 5 cm H2O. The peak
inspiratory flow was 80 L/min, FIO2 was
1.0, and peak (Ppeak) and plateau pressures (Pplat) were 94 and 40 cm H2O
respectively. Intrinsic PEEP (PEEPi) was
20 cm H2O. An arterial blood gas (ABG)
showed pH 7.21, PaCO2 54 mm Hg, and
PaO2 442 mm Hg. Laboratory data including chemistry and complete blood count
were all within normal limits. Urine
drug-of-abuse screen was negative. Chest
radiography demonstrated bilateral hyperinflated lungs, subcutaneous emphy477
sema, and pneumomediastinum. To decrease the inspiratory:expiratory ratio,
the inspiratory flow rate was gradually
increased to 120 L/min and tidal volume
was decreased to 400 mL, which resulted
in a Ppeak 100 cm H2O, and Pplat 34 cm
H2O. Subsequent ABGs demonstrated
worsening of acute respiratory acidosis
(pH 6.99, PaCO2 120 mm Hg, and PaO2 93
mm Hg with an FIO2 of 0.6). Aminophylline and sodium bicarbonate infusions
were started. High PEEPi (20 cm H2O)
induced transient mild hypotension and
prompted decreasing the respiratory rate
to 7 breaths/min, which reduced PEEPi
to 14 cm H2O and increased systolic
blood pressure to 100 –110 mm Hg. Repeated ABGs following these changes
showed PaCO2 oscillating between 180
and 185 mm Hg for 4 hrs, as demonstrated in Figure 1. Lack of improvement
in PaCO2 and worsening hypoxemia (PaO2/
FIO2 140 mm Hg) after the initial 6 hrs of
treatment prompted the start of isoflurane by inhalation delivered via an Ohmeda 7000 anesthesia ventilator (DatexOhmeda, Madison, WI). Initial manual
bag ventilation before the patient was
placed on the anesthesia ventilator resulted in the development of bilateral
pneumothoraces that were decompressed
by tube thoracostomies. An ABG obtained
after the patient had been on the anes-
thesia ventilator for 2 hrs demonstrated a
pH of 6.68, a PaCO2 of 202 mm Hg, and a
PaO2 of 162 mm Hg. Because of lack of
improvement in clinical status, worsening hypercapnia and low exhaled tidal
volumes (~100 mL), the patient was disconnected from the anesthesia ventilator.
Three hours after the resumption of ventilation using a Puritan-Bennet ventilator, an ABG revealed a PaCO2 of 180 mm
Hg and peak and plateau pressures were
94 and 32 cm H2O, respectively. Over the
next 8 hrs, her airway pressures and
ABGs improved such that the patient’s
PaCO2 was 80 mm Hg 36 hrs after admission to ICU and sodium bicarbonate and
neuromuscular blockade infusions were
discontinued. At 48 hrs, the patient continued to improve with near normalization of PaCO2 and peak airway pressures.
The chest tubes were subsequently removed and the patient was extubated on
the fourth and fifth hospital days, respectively. The patient developed generalized
weakness, presumably secondary to neuromuscular blockers and corticosteroids.
Electromyographic studies showed small,
short-duration, polyphasic motor unit action potentials and were consistent with a
myopathic process with an increase in
creatine phosphokinase, which peaked at
3500 U/L before returning to normal. Because of persistent generalized weakness,
the patient was discharged to a rehabilitation facility on the eighth hospital day.
Motor strength returned to normal by 8
wks after discharge.
CASE 2
Figure 1. Patient 1. Arterial blood gas analyses
during the initial 36 hrs of admission.
478
A 28-yr-old woman with moderate
persistent asthma presented to the emergency department with 2 days history of
increasing dyspnea and wheezing. Initial
examination revealed a respiratory rate of
30 breaths/min and diffuse wheezing with
a prolonged expiratory phase. She was
treated with nebulized albuterol continuously and intravenous corticosteroids.
Her initial ABG revealed pH 7.27, PaCO2
53 mm Hg, and PaO2 128 mm Hg while
wearing a face mask with high-flow oxygen and continuous albuterol. Shortly
thereafter, the patient complained of
worsening dyspnea, and after 0.5 mL of
epinephrine (1:1000) subcutaneously, the
patient vomited a large quantity of gastric
contents and lost consciousness. After intubation, a large, unmeasured quantity of
gastric contents was suctioned from the
endotracheal tube. Subsequently, the patient was heavily sedated and while being
ventilated manually at 10 breaths/min
with a bag/valve device, had a pH 7.07 and
a PaCO2 of 107 mm Hg. She was given
nebulized albuterol and ipratropium bromide via the endotracheal tube, and intravenous aminophylline, before transfer
to the ICU.
Upon arrival in the ICU the patient,
was ventilated with an Hamilton Veolar
ventilator (Hamilton Medical, Reno, NV)
set to assist control mode at 16 breaths/
minute, tidal volume of 450 mL (7.5 mL/
kg), PEEP of 5 cm H2O, peak inspiratory
flow rate of 130 L/min, and FIO2 of 1.0.
The patient was sedated with lorazepam
and fentanyl and paralyzed with vecuronium. The peak and plateau pressures
were 85 and 36 cm H2O, respectively. A
repeat ABG showed worsening respiratory acidosis, pH 6.99, PaCO2 145 mm Hg,
and PaO2 130 mm Hg. A supine anteroposterior chest radiograph showed bilateral infiltrates, a deep-sulcus sign on the
left, and pneumomediastinum for which
a thoracostomy tube was placed into the
left hemithorax. In addition to continuous nebulized albuterol, the patient received magnesium (4 g intravenously
over 30 mins followed by an infusion of 1
g/hr), and a sodium bicarbonate drip. The
ventilatory rate was reduced to 10
breaths/min because of high PEEPi (18
mm Hg) but a subsequent ABG showed
pH 6.90, PaCO2 218 mm Hg, and PaO2 153
mm Hg. At that point, inhalation anesthesia was begun using isoflurane. High
Ppeak required that inhalation anesthesia
be delivered via continuous manual bagging via the circle system of an anesthesia
ventilator (Ohmeda 7000, Datex-Ohmeda). Isoflurane was initially administered at an inspired concentration of 5%
and then titrated down to 1% to 2% because of systolic blood pressures ⬍90
mm Hg. While on isoflurane therapy,
peak airway pressure decreased from 85
to 62 cm H2O within 1 hr and fell further
to 50 cm H2O after approximately 8 hrs,
which allowed use of the anesthesia ventilator set to produce an exhaled tidal
volume of 400 –500 mL. As shown in Figure 2, inhalational agents were associated
with progressive improvement in ventilation and oxygenation. An ABG obtained
while the patient was receiving isoflurane
showed improved pH (7.07) and diminished PaCO2 (120 mm Hg). The patient
was continued on inhalation anesthesia
for approximately 30 hrs, during which
time her airway pressures and ABGs continued to improve.
Crit Care Med 2002 Vol. 30, No. 2
Figure 2. Patient 2. Arterial blood gas analyses
during the initial 36 hrs of admission.
The patient was later noted to have a
peak serum creatine phosphokinase level
of 37,830 U/L, with a rising creatinine of
2.0 mg/dL from an admission value of 1.1
mg/dL. General anesthesia and paralysis
were discontinued toward the end of day
2. Over the next 2 days, the patient improved, which allowed for extubation on
the fifth hospital day. She was transferred
to an intermediate care unit the following
day where she continued to improve with
normalization of creatine phosphokinase.
Electromyographic studies obtained on
the eighth hospital day were consistent
with a myopathic process (small, shortduration, polyphasic motor unit action
potentials). She was discharged on the
11th hospital day with physical therapy at
home. Two months later, she was doing
well and her asthma was clinically stable.
DISCUSSION
These two cases illustrate important
issues in the treatment of severe status
asthmaticus with extreme hypercapnia.
First, they support current understanding regarding the safety of permissive hypercapnia, even at very high levels of
PaCO2, for prolonged periods as encountered in these patients. The evolution of
hypercapnia, acidosis, and PaO2/FIO2 for
each patient is presented in Figures 1 and
2. PaCO2 ⬎150 mm Hg and pH ⬍7.0 persisted for 16 hrs in the first patient and
Crit Care Med 2002 Vol. 30, No. 2
for 9 hrs in the second one. Second, both
cases address the limitations of anesthesia ventilators in the setting of very high
airway resistance.
Permissive Hypercapnia. The vast majority of patients with asthma exacerbations
are successfully managed with conventional therapy including corticosteroids, inhaled ␤2-adrenergic agonists, and oxygen,
without the need for assisted ventilation.
Additional adjunctive therapies, including
helium-oxygen mixture, magnesium, and
aminophylline, are also sometimes helpful
in patients who do not respond promptly
(2). Approximately 2% of patients hospitalized for acute asthma require ventilatory
assistance (3, 4). Permissive hypercapnia or
controlled hypoventilation has become a
commonplace strategy to limit complications of mechanical ventilation (e.g., volutrauma) that may result from extreme
dynamic hyperinflation (1, 2, 5). Permissive
hypercapnia is defined as limitation of alveolar ventilation with acceptance of elevated arterial CO2 concentrations to protect
the lungs against large tidal volume ventilation (volutrauma) and hemodynamic
consequences of increased intrathoracic
pressures (5, 6). Several studies that incorporated permissive hypercapnia into the
ventilatory management of acute respiratory failure suggest that moderate levels of
hypercapnia are well tolerated and carry
few deleterious effects, thus outweighing
the potential adverse affects of hypercapnia.
Furthermore, it has been suggested that in
the setting of acute organ injury, hypercapnia may be protective whereas hypocapnia
may worsen the underlying organ dysfunction (7). The beneficial effects of hypercapnia may be attributable to acidosis-related
attenuation of reactive oxygen species formation and apoptosis (8, 9).
Although there is no consensus on the
level of hypercapnia that is safe, most
physicians avoid PaCO2 levels ⬎100 mm
Hg. A major concern regarding permissive hypercapnia is the development of
intracellular acidosis. Acute hypercapnia
causes a decrease in intracellular and extracellular pH. Intracellular pH returns
to 90% of normal within 3 hrs as a result
of effective intracellular buffers (e.g., proteins and phosphates), reduced proton
generation, and changes in transmembrane ion exchange (1, 10). Thus, in normoxic environments acute hypercapnia
has limited potential for inducing severe
intracellular acidosis and related cytotoxicity (11–13). The major contraindication
for permissive hypercapnia is related to
the vasodilatory effects of CO2 on cerebral
T
his report illustrates the challenges of mechan-
ical ventilation in severe
status asthmaticus, supports
the notion that permissive
hypercapnia is relatively
safe, and highlights the need
for careful forethought in
the use of inhalational anesthetics for the treatment of
status asthmaticus.
vessels. Cerebral blood flow reaches its
maximum at PaCO2 levels of ~120 mm Hg
(14), which may increase intracranial
pressure and aggravate preexisting intracranial hypertension (e.g., space-occupying lesion, head trauma, and severe hypertension) (1). Whereas hypercapnia in
the absence of hypoxemia has not been
associated with cerebral edema in experimental models (15), permissive hypercapnia can cause subarachnoid hemorrhage and cerebral edema in humans
(16 –18). Clinical reports of hypercapniainduced intracranial hypertension and resulting cerebral edema include fixed, dilated pupils (17, 18), quadriparesis,
hyperreflexia, and extensor plantar reflexes (19). Most of these neurologic findings are reversible and resolve with improvement in hypercapnia and intracranial
pressure. In the absence of a preexisting
cerebral disease, hypercapnia-associated intracranial hypertension appears to be well
tolerated (20). Hypovolemia is also a contraindication, as acute hypercapnia can
cause a transient fall in cardiac contractile
force (by interfering with the response of
myofilaments to calcium) and precipitate
cardiovascular collapse, particularly during
low inotropic states (21, 22).
Inhalational Anesthetics. Inhalational
anesthetics are potent bronchodilators
and have been successfully used in the
management of status asthmaticus refractory to conventional therapy. However, they are generally reserved for the
most refractory cases. Inhalational anes479
thetics have been shown to decrease airway resistance, dynamic hyperinflation,
and intrinsic positive end-expiratory
pressure (23). They result in rapid bronchodilatory response as a result of relaxation of airway smooth muscle (23), and
their use has been associated with early
liberation from mechanical ventilation
(24). Several case reports describe the
successful use of inhalational anesthetics
in the management of refractory asthma
(24 –27). A limitation is that even though
readily available, internists as well as intensivists not trained in anesthesia may
not be familiar with the anesthesia ventilators and the inability of these ventilators to ventilate against increased airway
resistance. These ventilators differ from
the commonly used ICU ventilators in
their flow and pressure capabilities. Specifically, these ventilators are not capable
of generating inspiratory pressures sufficient to ventilate patients with severely
elevated airway resistance. The decrease
in inspiratory flow that occurs with increasing airway pressure limits the tidal
volume delivered and therefore maximal
minute ventilation of anesthesia ventilators (28). In fact, mean inspiratory flow
decreases to only 40 L/min when Ppeak
reaches 60 cm H2O and continues to decrease further with increasing airway
pressure. Because of these limitations, as
in the first case presented, inhalation anesthesia may be more hazardous than
beneficial. New anesthesia ventilators
(e.g., Ohmeda 7810, Datex-Ohmeda) have
increased flow capabilities and anesthetic
agents can be administered via modified
Siemens Servo 900D ventilators (Siemens Medical Systems, Iselin, NJ) (29). If
neither is available, the alternative is
manual bagging until the airway pressure
is low enough to allow the use of an
anesthesia ventilator.
Although many physicians feel uncomfortable with PaCO2 levels above 80 –
100 mm Hg, several case reports indicate
that short durations of extreme hypercapnia (⬎150 mm Hg) are well tolerated (13,
30, 31). A recent report described the case
of an asthmatic patient who had a maximum PaCO2 of ~200 mm Hg for 10 hrs
with no immediate or late consequences
(32). The patients we report had PaCO2
levels that are among the highest reported in the medical literature. This extreme hypercapnia was the result, in part,
of the limited ability of commonly available anesthesia ventilators to deliver inhalational agents. Importantly, both pa480
tients recovered fully despite prolonged,
extreme hypercapnia. Both patients had
complications related to very high airway
pressures and difficulties associated with
the use of inhalational anesthetics, however, both recovered with no major consequences attributable to prolonged hypercapnia.
16.
17.
18.
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