Copyright ©ERS Journals Ltd 1998
European Respiratory Journal
ISSN 0903 - 1936

Eur Respir J 1998; 12: 235–237
DOI: 10.1183/09031936.98.12010235
Printed in UK - all rights reserved

CASE STUDY

Cerebral air embolism complicating bilevel positive airway
pressure therapy
S-C. Hung*, H-C. Hsu**, S-C. Chang+
aa

Cerebral air embolism complicating bilevel positive airway pressure therapy. S-C. Hung,
H-C. Hsu, S-C. Chang. ERS Journals Ltd 1998.
ABSTRACT: A 13 yr old male with acute lymphoblastic leukaemia who received
bilevel positive airway pressure ventilation via a face mask for post-transplant pneumonitis developed subcutaneous emphysema, radiographic evidence of pulmonary
interstitial emphysema, pneumomediastinum and 6 h later, right hemiparesis and
focal livedo reticularis. This case illustrates that severe barotrauma may complicate
noninvasive bilevel positive airway pressure ventilation.
Eur Respir J 1998; 12: 235–237.

Most forms of barotrauma including pulmonary interstitial emphysema, pneumomediastinum, pneumothorax,
pneumoperitonium and subcutaneous emphysema commonly occur in both adult and paediatric patients placed
on mechanical ventilation. However, barotrauma is considered to be rare in patients receiving noninvasive positive pressure ventilation (NPPV) as bilevel positive airway
pressure (BiPAP) ventilation. In this report, an unusual
case is presented of pulmonary barotrauma in a 13 yr old
leukaemic patient with post-transplant pneumonitis who
developed pulmonary barotrauma and possibly cerebral air
embolism while being noninvasively ventilated with BiPAP.
Case report
A previously well 13 yr old male was admitted to our
hospital in February 1997 because of a one-month history
of pallor, fatigue and febrile episodes. Physical examinations showed splenomegaly and purpura over the lower
limbs. The blood biochemistries were within normal ranges.
The complete blood count revealed a haematocrit of 16.0%,
a white blood count of 21.9×109 cells·L-1 with 74% lymphoblasts and a platelet count of 29×109 cells·L-1. Haematological malignancies were highly suspected and a bone
marrow aspiration was performed. Microscopic examination of the bone marrow aspirate revealed >90% of lymphoblasts. A diagnosis of acute lymphoblastic leukaemia
was established.
Chemotherapy with vincristine, prednisolone, daunorubicin, and asparaginase was started. The patient's postchemotherapy course was complicated by acute pancreatitis
and hyperglycaemia. Because complete remission was not
achieved after induction chemotherapy, the regimen was
switched to cytosine arabinoside for 7 days and daunorubicin for 3 days (A7D3) and additional cytosine arabinoside for 5 days and idarubicin for 2 days (A512). Repeated
bone marrow examination, however, still showed excessive lymphoblasts. On April 15, cytosine arabinoside and

*Dept of Medicine, **Division of Hematology, and +Chest Dept, Veterans General
Hospital, Taipei, Taiwan, ROC. School of
Medicine, National Yang-Ming University,
Taipei, Taiwan, ROC.
Correspondence: S-C. Chang, Chest Dept,
Veterans General Hospital, 201 Sec 2, ShihPai Road, Taipei, Taiwan 11217, ROC, Fax:
886 2 28752380
Keywords: Barotrauma, bilevel positive airway pressure, cerebral air embolism, pulmonary interstitial emphysema
Received: December 10 1997
Accepted after revision March 16 1998

novantrone were administered. High-dose methotrexate chemotherapy was performed on April 29 because of refractory leukaemia. On May 5, he began to receive buffy coat
transfusion from his father, but the response was poor. He
then agreed to have an allogeneic transplantation.
The patient underwent allogeneic peripheral blood stem
cell transplantation (PBSCT) on May 22 following conditioning with cyclophosphamide and total body irradiation.
On day 10 after transplantation, a grade III acute graft versus host disease developed but resolved after immunosuppressive therapy. He was treated with broad-spectrum
antibiotics and frequent blood transfusions for his prolonged pancytopenia and fever. Prophylactic gancyclovir
against cytomegalovirus (CMV) was also given. His condition stabilized. On July 20, 58 days post-transplant, progressive dyspnoea developed. A chest radiograph showed
diffuse interstitial pulmonary infiltrates. Sputum cultures
yielded normal mixed flora and multiple blood cultures
grew no micro-organisms. Further invasive studies were
not performed because of the patient's reluctance. Combinations of high-dose steroids, i.v. trimethoprim (TMP)/
sulphamethoxazole (SMX) and gancyclovir were administered for the interstitial pneumonitis. In addition, BiPAP
therapy via a nasal mask was applied with an inspiratory
positive airway pressure (IPAP) of 16 cmH2O, an expiratory positive airway pressure (EPAP) of 5 cmH2O and an
oxygen flow of 12 L·min-1 to maintain the arterial oxygen
saturation (Sa,O2) above 90%. The patient suffered from
severe diarrhoea for the next week. The CMV immunoglobulin (Ig)M became positive at the same time. His clinical
features were thought to be related to CMV pneumonitis
and enteritis.
On August 3, after 2 weeks of BiPAP therapy, he was
found to have subcutaneous emphysema over the right
anterior chest accompanied by localized skin marbling.
A chest radiograph was taken immediately and revealed
pneumomediastinum (fig. 1). Six hours later, the patient

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S-C. HUNG ET AL.

Discussion

Fig. 1. – Anteroposterior chest radiograph revealing fine streaks of air
(arrows) within mediastinum, extending upwards to the neck.

suddenly noticed weakness of his right side limbs. Physical examination revealed right hemiparalysis, but no
heart murmur or carotid bruit suggestive of cardiogenic or
thrombotic embolism. A noncontrast computed tomography (CT) scan of the brain showed a low attenuation over
the posterior limb of internal capsule of the left cerebrum
(fig. 2), a finding consistent with cerebral infarction. A
diagnosis of cerebral arterial air emboli was considered.
The inspired oxygen fraction was increased and the headdown position was adopted. However, his neurological
deficit showed only little recovery. Over the next 5 days,
the patient had worsening dyspnoea. The subcutaneous
emphysema extended progressively down to his right forearm. Arterial blood gas analysis (IPAP 14 cmH2O, EPAP 5
cmH2O, O2 15 L·min-1, respiratory frequency 24 breaths·
min-1) showed an arterial oxygen tension (Pa,O2) of 5.5 kPa
(41 mmHg), an arterial carbon dioxide tension (Pa,CO2) of
4.0 kPa (29.5 mmHg) and a pH of 7.446. He was intubated and assisted with mechanical ventilation. However,
the Sa,O2 could not be elevated and the patient died of respiratory failure.

Fig. 2. – Computed tomography scan of the brain showing a low attenuation (arrow) over the posterior limb of the internal capsule of the left
cerebrum.

BiPAP ventilation, a form of NPPV, has been widely
used in both acute and chronic respiratory failure in the
1990's. In selected patients, NPPV can avoid the need for
intubation and reduce the complication and mortality rate
[1]. In general, NPPV is safe and well tolerated. Among
the few side-effects, most are due to interface-related discomforts [2]. Pulmonary barotrauma, though an important
complication of positive pressure ventilation, had seldom
been reported in patients receiving NPPV. Pulmonary barotrauma is related primarily to both the airway pressure
and the associated pulmonary pathology. It is considered
to be a rare event in patients receiving NPPV because of a
relatively low inspiratory pressure and stable pulmonary
condition. With the increasing use of NPPV therapy in the
current critical care, however, barotrauma can be expected
to occur more frequently.
When the airway pressure is elevated by increasing the
IPAP and EPAP, or the pulmonary tissue is destroyed by
the inflammatory process, gas in the alveoli may follow
the path of least resistance and rupture into the interstitium, producing the radiographic manifestations of interstitial emphysema. It then moves centrally within the
bronchovascular sheath and dissects into the mediastinum,
or travels along the fascial planes into the neck or trunk,
resulting in pneumomediastinum and subcutaneous emphysema [3]. Previous studies have indicated that 40 cmH2O
is a clinically important peak airway pressure level above
which barotrauma is likely to occur. Other investigators
believe that positive end-expiratory pressure (PEEP) is the
most significant factor [4]. However, in those patients who
have severe pre-existing lung disease, especially emphysema, necrotizing pneumonia and adult respiratory distress syndrome, even a low airway pressure may cause
damage to the alveolar wall and air leakage.
It is possible for extra-alveolar air to enter the systemic
circulation if there is bronchovenous communication and
an adequate pressure gradient. Gas that has ruptured from
alveoli into the bronchovascular sheath may preferentially
enter the pulmonary venous system if the vascular structures have been disrupted by a necrotizing process [3]. We
suspect that this was the case with our patient. Even if a
small amount of gas enters the systemic circulation from
the pulmonary vein, it can lead to catastrophic embolic
events including stroke and acute myocardial infarction.
Despite of its striking clinical presentations, the presence
of gas in the systemic circulation is difficult to prove
because a very small amount of intravascular gas is able to
produce life-threatening symptoms but is cleared quickly.
Furthermore, the direct demonstration of intravascular gas
often requires computer-enhanced image studies or surgery, which are not always practical or safe for use in critically ill patients [5].
Our patient developed an abrupt onset of right hemiparalysis 2 months after the allogeneic PBSCT. Stroke is
infrequent in patients receiving allogeneic bone marrow
transplant. In a recent review of neurological complications in 425 patients who underwent bone marrow transplantation (310 allogeneic, 115 autologous) for leukaemia,
the most common complications were central nervous
system (CNS) haemorrhage (3.8%), metabolic encephalopathy (3%) and CNS infection (2%). Only two patients
had ischaemic disorders [6]. In the other report examining

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CEREBRAL AIR EMBOLISM COMPLICATING BIPAP

the clinical and autopsy findings in 78 patients who died
after bone marrow transplantation, CNS infarct was found
in three patients and was associated with endocarditis in
all cases. Nonbacterial thrombotic endocarditis was found
in five patients and was the cause of cerebral infarction in
two. Acute bacterial endocarditis due to enterococcus occurred in one patient and was also the cause of a cerebral
infarction [7]. Our patient did not have clinical evidence
of bacterial endocarditis or a hypercoagulable state.
Although the possibility of nonbacterial thrombotic
endocarditis, the most frequent cause of stroke in the transplant recipient cannot be completely excluded, without an
echocardiographic document, the subsequent development
of stroke after subcutaneous emphysema strongly supports a causal relation. Further evidence that makes the
clinical diagnosis of cerebral air emboli beyond much
doubt is the presence of localized skin marbling and focal
livedo reticularis. This unusual dermal feature represents
venodilation in response to arteriolar occlusion and is considered a definitive clinical sign of gas embolism [5, 8].
Cerebral air embolism may occur following diving accidents [9], neonatal respiratory distress syndrome [10],
cardiovascular surgery, neurosurgery and central line placement [11]. To our knowledge, this is the first report of its
association with BiPAP therapy.
Classically, a CT scan of brain may reveal intravascular
air within the cranium if the image study is performed
early enough after the occurrence of cerebral air embolization. Resolution of the air-density lesion with a residual
area of low density consistent with infarction will be observed on the later scan, but the time needed for resolution
varies with the individual. Our patient was noted to have a
lacunar infarction, which usually develops in patients with
long-term hypertension. A similar finding was reported in
a 23 yr old male with end-stage renal disease who suffered
from bilateral small infarcts around thalamic regions as an
iatrogenic cerebral air embolism during the placement of
an arteriovenous fistula [12]. Accordingly, cerebral air embolism might present as lacunar syndrome in previously
normotensive patients.
After a careful review of the patient's chest film (fig. 3)
1 day before the development of cerebral air embolism,
pulmonary interstitial emphysema, the earliest sign of alveolar rupture, was observed. This condition is identified
radiographically as small parenchymal cysts, perivascular
halos, linear streaks of air radiating toward the hilum,
pneumatoceles or subpleural air [4]. Pulmonary interstitial
emphysema is a space-occupying lesion which compresses the surrounding lung parenchyma. It may severely impair the patient's already compromised respiratory ability
and is the forecast of impending severe barotrauma [4].
This case demonstrated the fact that the bilevel positive
airway pressure therapy is not as safe as is generally assumed. Accordingly, clinicians should always be aware of
the subtle radiographic changes in pulmonary barotrauma,
even in patients receiving bilevel positive airway pressure
therapy. Once pulmonary interstitial emphysema develops, respiratory therapeutic strategies or alternative ventilatory modes should be considered to ameliorate the airway
pressure aggressively [5]. Preparations for the management of barotrauma should be made if the above efforts
fail to resolve the condition.

Fig. 3. – Anteroposterior chest radiograph showing perivascular halos
(thick arrows) against a consolidated lung, and linear streaks of air (thin
arrows) representing large vessels surrounded by circles of air within
the perivascular sheath. Subpleural air (arrowheads) is also present.

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