treat hypoventilation disorders. 12 Although plasma proges-Progesterone and estradiol are metabolized in the terone is elevated in cirrhotic patients because of decreased liver and are elevated in patients with cirrhosis. Progeshepatic metabolism, progesterone has not been proved to terone stimulates ventilation by activating progesterone cause their hyperventilation. receptors in the central nervous system; estradiol may
We propose estradiol as a contributing factor to respiratory facilitate progesterone's actions by increasing progesalkalosis, although this has not been examined in humans. terone receptors. This study evaluated whether proges-Estradiol is metabolized by the liver into estriol, which has terone and estradiol contribute to the respiratory alkaminimal estrogen effects. Estradiol has no direct respiratory losis common in cirrhotic patients. Arterial blood gases stimulatory effect; 13 however, estradiol increases the number and progesterone and estradiol levels were obtained in of progesterone receptors in animals and may facilitate pro-50 patients with cirrhosis. Multiple linear regression regesterone's actions. 14,15 vealed a statistically significant correlation between This report examines the roles of hyperprogesteronemia P a CO 2 and progesterone and estradiol (r Γ
.54, P Γ΅ .05). and hyperestradiolemia in producing hyperventilation in pa-Patients with severe hyperventilation (P a CO 2 Β°30 mm tients with cirrhosis. Hg) had statistically higher levels of progesterone and estradiol than did patients with mild hyperventilation PATIENTS AND METHODS (30 Γ΅ P a CO 2 Β°35) or normal ventilation (P a CO 2 ΓΊ 35) (P Γ΅ .
05). Although the progesterone levels were two orders
With written patient consent and approval from the University of of magnitude lower than those associated with hyper-Rochester Investigational Review Board, we prospectively studied 50 ventilation in pregnant patients, the increased ventilapatients presenting to liver clinic for possible liver transplantation. tory effect may be because of the altered blood-brain Premenopausal women, patients with chronic obstructive pulmonary disease or acute encephalopathy, or patients taking hormonal medibarrier (BBB) present in cirrhotic patients. Progestercations, narcotics, or benzodiazepines were excluded. All patients one and estradiol appear to contribute to the hypervenwere afebrile. One percent lidocaine was injected subcutaneously tilation in cirrhotic patients. (HEPATOLOGY 1997;25:55through a 25-gauge needle above the right or left radial artery at
58. )
the wrist. A 20-gauge catheter was then placed in a sterile fashion into the radial artery and taped in place. To ensure no hyperventilation from anxiety or pain, arterial blood was drawn into a heparinized Respiratory alkalosis is common in patients with hepatic syringe after several minutes, the arterial blood was placed on ice, cirrhosis 1,2 although the cause has proved elusive. Proposed and sent to the lab for immediate determination of blood gas results. mechanisms include increased ammonia, 3 decreased albu-Blood was also sent for determination of estradiol and progesterone min, 4 hypoxia, 5 and elevated progesterone. 6 levels. Albumin and bilirubin levels and prothrombin time were de-Hyperammonemia is common in cirrhotic patients; ammotermined from venous blood obtained approximately 2 weeks before nia, however, has not been shown to correlate with minute this procedure. ventilation, 3 and ammonia infusions did not decrease P a CO 2
The estradiol and progesterone levels were measured by Immulite in volunteers. 7 In an interesting study, hypoalbuminemic pachemiluminescent enzyme immunoassays (Diagnostics Products tients with and without cirrhosis had a respiratory alkalosis Corporation, Los Angeles, CA). The arterial blood gases were mea- sured on a Corning 288 blood gas analyzer (Ciba-Corning Diagnostics inversely related to albumin level. 4 The study did not address Corporation, Medfield, MA). Total bilirubin and albumin were meathe reasons for this result. Patients with cirrhosis often have sured on a Vitros dry chemistry analyzer (Johnson & Johnson, Rochhypoxia from multiple causes including intrapulmonary ester, NY). An optical MDA 180 coagulation analyzer (Organon Tekshunting, impaired hypoxic pulmonary vasoconstriction, asnika Corporation, Durham, NC) measured prothrombin times. cites, and pleural effusions. 8,9 The mild degree of hypoxia Statistical Analysis. Patients were divided into three groups based present in cirrhotic patients has not been shown to cause on P a CO 2 (mm Hg): normal ventilation (P a CO 2 ΓΊ 35), mild hyperven- hyperventilation. 5 tilation (35 Β’ P a CO 2 ΓΊ 30), and severe hyperventilation (P a CO 2 Β°Progesterone produces hyperventilation as shown by the 30). Patients were also divided into Childs' classification groups A, high correlation between P a CO 2 and the log of serum proges-B, and C. 16 Differences among groups were determined using one way ANOVA with Kruskal-Wallis testing if necessary; P Γ΅ .05 was terone levels in pregnant patients. 10 Medroxyprogesterone accepted as significant.
increases ventilation 11 and has been used successfully to
Results
The data from one patient was discarded because the pro-Abbreviations: BBB, blood-brain barrier; CSF, cerebrospinal fluid. gesterone level was ΓΊ 10 SDs above the mean. Forty-five From the Departments of 1 Anesthesiology and 2 Transplant Surgery at the University patients (92%) had blood drawn between 9 AM and 12 PM to