Case Discussion 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)。 繼續教育考題 1. (C) Which of the following descriptions is not compatible with the initial ABG data of this patient? A The presence of metabolic acidosis B The presence of alkalemia C The presence of metabolic alkalosis D The presence of respiratory alkalosis 2. (A) Which of the following PaCO2 levels is most likely for the compensation for a metabolic acidosis with a bicarbonate level of 11.1 mEq/L? A 24 mm Hg B 32 mmHg C 14 mmHg D 18 mm Hg 3. (A) The lower limit for [HCO3-] in the compensation for a respiratory alkalosis is about A 14-16 mmHg B 18-24 mmHg C 6-8 mmHg D 20-240 mmHg 4. (D) Which of the following descriptions about the clinical futures of central neurogenic hyperventilation is true? A Decreased PaCO2 B Elevated PaO2 C Respiratory alkalosis in the absence of radiographic evidence of pulmonary disorders D All of the above 5. (D) Which of the following descriptions of central neurogenic hyperventilation is true? A Usually seen in deeply comatose patients who have serious CNS injuries due to head trauma, stroke, and infection. B Tumors of the CNS can also produce CNH. C Patients with tumor-induced CNH may be awake because the reticular-activating system is not affected by the tumor in the early stages of the condition. D All of the above 6. (B) Which of the following descriptions of tumor-induced central neurogenic hyperventilation is WRONG? A The most frequent cause is lymphoma, primary or secondary B Hyperventilation often subsides during sleep C Is a rare condition for primary and metastatic brain tumors D Patients with unexplained severe hyperventilation should undergo brain imaging studies and lumbar puncture 7. (B) For tumor-induced central neurogenic hyperventilation, the most frequently involved site is: A The cerebellum B The pons C The cerebral cortex D The thalamus 8. (D) Which description about the control of rhythmic breathing within the CNS is true? A The medullary center is the main coordinating center of breathing, sending efferent impulses. B The apneustic center in the pons acts on the medulla to promote deep and prolonged inspiration, whereas the pontine pneumotaxic center inhibits inspiration. C It has been postulated that the damaged medial pontine structures might result in disconnection of inhibitory pathways from the respiratory center in the medulla. D All of the above 9. (D) What of the following conditions may lead to a mixed disorder with both metabolic acidosis and respiratory alkalosis? A Salicylate intoxication B Lactic acidosis and septic shock C Pulmonary embolism in the presence of renal insuffiency D All of the above 10. (D) Which description is true regarding the management of tumor-induced central neurogenic hyperventilation? A Most patients are supported by mechanical ventilation and managed with paralytic agents to control their hyperventilation until more specific therapy for the CNS lesions can take effect. B This condition usually ends fatally in a few weeks C Some patients may respond to brain irradiation or systemic chemotherapy D All of the above

答案解說 答案解說: (C) pH of 7.65; PaO2, 184.9 mmHg; PaCO2, 9.7 mmHg; HCO3- 11.1 mEq/L; and base deficit, - 7.8 mEq/L. (nasal cannula 3 L/min) : Clinical condition was compatible with septic shock with lactic acidosis, but the PaCO2 was too low and pH level was unusually high. So there must be a strong stimulus for hyperventilation which resulted in respiratory alkalosis. There was no evidence of metabolic alkalosis in this patient. (A) According the the equation: PaCO2 = [(HCO3 x 1.5) + 8 ± 2] = 11.1 x 1.5 + 8 ± 2 = 22.5-26.5 (mmHg) (A) The lower limit for [HCO3-] in the compensation of a respiratory alkalosis is about 15 mmHg (D) All descriptions are correct. Central neurogenic hyperventilation (CNH) was defined by Plum and Swanson in 1959 as a syndrome of decreased PaCO2, elevated PaO2,, and respiratory alkalosis in the absence of radiographic evidence of pulmonary congestion. (D) All descriptions are correct (B) Central neurogenic hyperventilation is a rare clinical condition and CNS lymphoma is the most common etiology. Hyperventilation in these patients often persists during sleep or light sedation. (B) The most frequently involved area is the pons (central pontine hyperventilation). But other sites may also be associated with this condition. (D) All descriptions are correct. There are at least three centers for the control of rhythmic breathing within the CNS: the medulla center, the pontine apneustic center, and the pontine pneumotaxic center. All descriptions are correct. (D) All three condition may lead to both respiratory alkalosis and metabolic acidosis. (D) All descriptions are correct. Top of Page