Brief
History
A 40 -year-old woman with previously diagnosed
non-Hodgkin's lymphoma was admitted to the ICU of National
Taiwan University Hospital because of a 2-day history of
fever, hypotension, and shortness of breath. The patient
denied headaches, vomiting, or blurred vision.
Three years earlier, she had
first presented for treatment with a mass in her right breast
that proved to be a diffuse, large, B cell-type lymphoma.
Complete remission was achieved after combination
chemotherapy. Unfortunately, the patient was unable to undergo
a stem-cell transplantation because intermittent fever,
chills, and progressive dyspnea developed 2 weeks after
chemotherapy, before peripheral stem cells could be harvested.
On examination the patient
was alert but in marked respiratory distress, with a
respiratory rate of up to 35 breaths/min. BP was 80/50 mm Hg;
pulse, 120 beats/min; and body temperature, 38.8°C. The neck
was supple. The jugular veins were not distended. The chest
was symmetrically expanded, with clear breath sounds. The
other physical findings and neurologic examinations were
unremarkable.
The chest radiograph
was normal. Results of laboratory tests were as follows:
leukocytes, 1.53 x 103/μL; hemoglobin, 10.6 g/dL; platelet
count, 179 x 103/μL; potassium, 2.9 mEq/L; magnesium, 0.62
mmol/L; and serum lactate level, 6.6 mmol/L (normal, < 2
mmol/L). The arterial blood gases with the patient receiving
O2, 3 L/min, by nasal cannula revealed: pH of 7.65; PaO2,
184.9 mm Hg; PaCO2
, 9.7 mm Hg; bicarbonate, 11.1 mEq/L;
and base deficit, - 7.8 mEq/L.
In the ICU, the patient's BP
normalized after fluid therapy, and the fever subsided after
the use of granulocyte-colony stimulating factor and
antibiotics. The lactate level was within normal limits 2 days
later. Nevertheless, the patient's hyperventilation persisted
(Table 1), with a respiratory rate that was maintained at 40
breaths/min. The patient's breathing did not slow during deep
sleep or after being sedated with oral flunitrazepam, 1 mg
bid, or alprazolam, 1 mg tid.
Table 1. Arterial Blood Gases After Admission to ICU
Time |
Condition |
RR/min |
pH |
PaCO2, mmHg |
PaO2, mmHg |
HCO3-, mEq/L |
BE, mEq/L |
Anion Gap, mEq/L
|
Day 1
|
O2 (nasal cannula 3 L/min) |
40 |
7.657 |
9.7 |
184.9 |
11.1 |
-7.8 |
20 |
Day 3
|
Room air and in deep sleep |
36 |
7.563 |
7.7 |
132.5 |
7.0 |
-14.7 |
13 |
Day 4
|
Breathing through a bag; sedated by
alprazolam |
33 |
7.531 |
8.6 |
135.9 |
7.1 |
-14.3 |
14
|
Course and
Treatment
The persistence of the patient's hyperventilation during
deep sleep and sedation suggested the presence of a CNS lesion
causing ongoing stimulation and/or disinhibition of her
respiratory center. Therefore, an MRI of the brain (Fig 1) was
performed, which demonstrated a small mass lesion in the left
medial temporal lobe and suspicious leptomeningeal enhancement
over both parietal regions. A lumbar puncture with cytologic
examination of the cerebrospinal fluid demonstrated lymphoma
cells, which supported the diagnosis of central neurogenic
hyperventilation (CNH) due to lymphomatous involvement of the
CNS.
The present patient received salvage chemotherapy with
BD-HDMA (carmustine, dexamethasone, high-dose methotrexate
with leucovorin rescue, and cytosine arabinoside). IV infusion
of morphine, 5 mg q6h; midazolam, 3 μg/kg/min; and propofol,
15 μg/kg/min, were effective in suppressing her respiratory
rate to 20 to 25 breaths/min, without the use of neuromuscular
blockade or mechanical ventilation (Table 2 ). She remained
arousable, and her hyperventilation gradually resolved within
1 week, enabling complete withdrawal of all respiratory
suppressants.
Table 2. Serial Data of Arterial Blood Gases After ICU
Management
Time |
Condition* |
RR/min |
pH |
PaCO2, mmHg |
PaO2, mmHg |
HCO3-, mEq/L |
BE, mEq/L |
Anion Gap, mEq/L |
Day 5 |
Morphine, 5 μg IV, q6h |
26 |
7.58 |
11.5 |
120.9 |
10.9 |
-9.4 |
14 |
Day 6 |
Midazolam, 3 μg/kg/min |
24 |
7.543 |
15.5 |
112.7 |
13.4 |
-7.5 |
13 |
Day 7 |
Propofol, 15 μg/kg/min |
22 |
7.43 |
16.5 |
116.3 |
10.8 |
-11.8 |
11 |
Day 19 |
Receiving chemotherapy |
25 |
7.53 |
22.4 |
128.5 |
18.9 |
-2.6 |
9 |
Day 33 |
Room air |
20 |
7.49 |
37.3 |
74.7 |
28.5 |
5.2 |
12 | * With patient
breathing room air
本病例為一淋巴瘤病患,雖經化學治療仍無法有效控制病情。
病人此次入ICU乃因高燒、血壓下降,且有白血球過低之現象,疑似有敗血症。病人呼吸型態呈現過度換氣之現象,
且在睡眠時或輕度鎮靜劑之使用下仍然持續。血液動脈氣體分析顯示有嚴重之鹼血症,二氧化碳過低,
HCO3-濃度也低,動脈血氧分壓則相當不錯。經輸液治療及抗生素使用後臨床血行動力學改善,
且陰離子間隙(anion gap)及乳酸濃度也回到正常,但過度換氣及ABG異常仍存在,且無法用正常之代償反應來解釋。病人
肺部並無異常,故必是存在一強烈之呼吸中樞之刺激造成過度換氣。經腦部之MRI攝影及CSF檢查證實本病患最可能產生中
樞性過度換氣現象。此為一罕見臨床病症,患者多為腦部有淋巴瘤侵犯。通常癒後不佳,許多病患需大量鎮靜劑
或morphine等以抑制嚴重之呼吸性鹼中毒(respiratory alkalosis)。
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