Hypercapnic and hypoxic ventilatory responses in parents and siblings of children with congenital central hypoventilation syndrome

Children with congenital central hypoventilation syndrome (CCHS) have abnormal ventilatory responses to metabolic stimuli. As there is a genetically determined component of chemoreceptor sensitivity, parents and siblings of children with CCHS may also have blunted ventilatory responses to hypercapnea and hypoxia. To test this, we studied hypercapnic ventilatory responses and hypoxic ventilatory responses in six mothers, four fathers, and five siblings (6 to 49 yr of age) of seven children with CCHS and compared them with 15 age- and sex-matched control subjects (5 to 47 yr of age). Pulmonary function tests were not different between relatives of children with CCHS and control subjects. To measure hypercapnic ventilatory responses, subjects rebreathed 5% CO2/95% O2 until PACO2 reached 60 to 70 mm Hg. To measure hypoxic ventilatory responses (L/min/% SaO2), subjects rebreathed 14% O2/7% CO2/balance N2 at mixed venous PCO2 until SaO2 fell to 75%. All tests were completed in less than 4 min. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory timing/total respiratory cycle timing) were calculated on a breath-by-breath basis. Hypercapnic ventilatory responses were 1.97 +/- 0.32 L/min/mm Hg PACO2 in children with CCHS relatives and 2.23 +/- 0.23 L/min/mm Hg PACO2 in control subjects. Hypoxic ventilatory responses were -1.99 +/- 0.37 L/min/% SaO2 in the relatives and -1.54 +/- 0.25 L/min/% SaO2 in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aging effects on the interaction of hypercapnia and hypoxia as ventilatory stimuli

We measured ventilatory responses to progressive hypercapnia at two steady-state levels of oxygenation and to progressive hypoxia at two steady-state levels of CO2 in 10 elderly and 10 young individuals. Under hyperoxic conditions, the ventilatory response to progressive hypercapnia was not significantly different between age groups but, under hypoxic conditions, the response to hypercapnia was lower in the elderly group. The interaction of hypercapnic and hypoxic stimuli was greater among young persons as indicated by a higher ratio of the hypercapnic response slopes (hypoxic/hyperoxic); 1.48 +/- 0.19 versus 0.98 +/- 0.11, p less than .05. The ventilatory response to hypoxia at the lower CO2 level was significantly greater among elderly than among young adults but not significantly different between age groups at the higher CO2 level. The ratio of hypoxic response slopes (high PCO2/lower PCO2) was 1.56 +/- 0.17 among elderly participants and 3.14 +/- 0.63 among young participants (p less than .05). These results suggest that aging diminishes the multiplicative effect of hypercapnia and hypoxia as ventilatory stimuli.     

Familial aspects of ventilatory control in patients with chronic obstructive pulmonary disease

To determine whether abnormal chemical drives to breathe in patients with chronic obstructive pulmonary disease (COPD) antedate the development of chronic CO2 retention, we measured ventilatory and P0.1 responses to hypercapnia and hypoxia in 14 such patients and 23 of their normal adult offspring. Hypoxic responses in the patients were positively correlated with the mean hypoxic responses of their offspring. Neither the hypercapnic responses nor the resting breathing patterns of the patients were related to those of their offspring. Hypoxic response was lower in offspring of hypercapnic patients than in offspring of normocapnic patients. Blunt hypoxic responses in patients with COPD are influenced by familial factors and may represent a premorbid "risk factor" in the development of CO2 retention in this disease. This does not appear to be true for hypercapnic response or breathing pattern.     

Severe short-term hypothyroidism is not associated with an increased incidence of myocardial ischemia as assessed by thallium-201 stress/rest myocardial scintigraphy.

Reversible silent myocardial ischemia associated with treatment of long-standing hypothyroidism has recently been reported using thallium-201 (201Tl) myocardial single photon emission tomography (SPET). The aim of the present study was to evaluate whether patients with short-term hypothyroidism (serum thyrotropin [TSH] levels above 30 mU/L) have an increased risk of silent myocardial ischemia. We studied 20 patients with differentiated thyroid carcinoma that had undergone thyroidectomy and ablative (131)I therapy. None of the patients had a known history of atherosclerotic cardiovascular disease. In the course of a planned follow-up examination, suppressive levothyroxine (LT4) therapy was discontinued 7 weeks prior to scintigraphy and replaced by triiodothyronine (T3) therapy for 4 weeks. No thyroid hormone medication was given during the 3 weeks preceding the diagnostic procedures. All patients were hypothyroid (TSH 87.2 +/- 30.8 mU/L, mean +/- SD) at the time of the examination. 20lTl-SPET was performed immediately after bicycle exercise stress test and again after a delay of 4 hours. In case of abnormal results, (n = 3) the examination was repeated after patients were euthyroid. Two patients showed effects of soft-tissue attenuation (breast attenuation in a female and diaphragmatic attenuation in a male subject). Myocardial ischemia was revealed in 1 patient but was seen in both hypothyroid and euthyroid examinations. The results of the present study show that short-term severe hypothyroidism as encountered in athyreotic patients after cessation of thyroxine medication for several weeks, is not associated with an impairment of myocardial perfusion.     

Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome.

Most patients with extreme obesity do not exhibit alveolar hypoventilation, but an intriguing minority do. The mechanism(s) of this phenomenon remain unknown. A disorder in ventilatory control has been suggested as a major factor in the pathogenesis of the obesity-hypoventilation syndrome. Accordingly, hypoxic and hypercapnic ventilatory drives were measured in 10 patients with the typical symptoms of the syndrome: obesity, hypersomnolence, hypercapnia, hypoxemia, polycythemia and cor pulmonale. Hypoxic ventilatory drive, measured as the shape parameter A, averaged 21.9 +/- 5.35, approximately one-sixth that in normal controls, A = 126 +/- 8.6 (P less than 0.01). The ventilatory response to hypercapnia also was markedly reduced, the slope of the response averaging 0.51 +/- 0.005, or about one-third the normal value of 1.83 +/- 0.13 (P less than 0.01). This decreased responsiveness in hypoxic and hypercapnic ventilatory drive was consistent throughout the group. The depression in ventilatory drive found in the obesity-hypoventilation syndrome may be causally related to the alveolar hypoventilation manifested by these patients.     

Peripheral chemosensitivity assessed by the modified transient O2 test in female twins

To evaluate genetic influence on the control of breathing in adult women, we measured, in healthy female twins, ventilatory responses to isocapnic progressive hypoxia and hyperoxic progressive hypercapnia, and the withdrawal response (the modified transient O2 test) which is considered to selectively reflect peripheral chemoreceptor activity. The withdrawal response was obtained as the magnitude of initial depression in ventilation induced by two breaths of O2 from steady-state hypercapnic hypoxia. Nine monozygotic twin pairs, aged 44 +/- SD17 years, and 7 dizygotic twin pairs, aged 39 +/- 8 years, were studied. Mean values for ventilatory responses to hypoxia and hypercapnia, and the withdrawal response were not different between MZ and DZ. The within-pair variance ratio (VDZ/VMZ) for the withdrawal response was significantly greater than one (p less than 0.05), although neither VDZ/VMZ for the hypoxic response nor that for the hypercapnic response was greater than one. These observations suggest that the peripheral chemosensitivity is influenced by genetic factors even in adult women, including aged subjects, when genetic influence is not apparent in the ventilatory responses to progressive hypoxia and hypercapnia.     

Theophylline does not increase ventilatory responses to hypercapnia or hypoxia.

Theophylline is commonly believed to stimulate central respiratory centers. We studied the effect of oral theophylline therapy on ventilatory responses to hypercapnia and hypoxia during a double-blind placebo-controlled trial with a slow release oral theophylline preparation. We measured hypercapnic and hypoxic ventilatory responses using rebreathing techniques in 15 subjects (21 to 41 yr of age, with normal lung function) on three occasions: baseline, after 4 days of Drug 1, and after 4 days of Drug 2. For subjects receiving theophylline, the mean serum theophylline level was 11.3 + 1.3 (SE) micrograms/ml (range, 5.3 to 22.1). Unpleasant side effects were reported by 11 of the 15 subjects (nausea, jitteriness, and agitation) while receiving theophylline but not while receiving placebo. The mean hypercapnic ventilatory response with placebo was 4.3 +/- 0.9 L/min/mm Hg PACO2 and with theophylline it was 4.5 +/- 0.7 L/min/%SaO2 and with theophylline it was -2.7 +/- 0.4 L/min/%SaO2. Hypoxic responses for each subject were measured at similar PvCO2. There were no significant changes in ventilatory responses with theophylline. We conclude that theophylline use, at a dose sufficient to cause side effects, does not affect chemoreceptor responsiveness.     

Alveolar hypoventilation syndrome. Studies of ventilatory control in patients selected for diaphragm pacing

The syndrome of nocturnal hypoventilation and/or apnea without major intrinsic lung disease is of greater surgical interest since the introduction of therapeutic diaphragm pacing. Of our 29 patients successfully managed by diaphragm pacing, we describe 17 in whom detailed studies of the ventilatory responses to hypoxia are available.The diagnosis was established by the following criteria: (1) an increase in arterial carbon dioxide tension (PaCO₂) (> 45 mm Hg) and a depression in the arterial oxygen tension (PaO₂) (< 75 mm Hg) at least during sleep; (2) respiratory arrests and/or apneic episodes during sleep; (3) near normal tests of ventilatory capacity; and (4) diminished ventilatory response to carbon dioxide breathing.New information on the ventilatory responses to hypoxia was obtained by a nonsteady state closed-circuit rebreathing method. The following were compared: (1) hypoxia with carbon dioxide variably absorbed so as to maintain base line PaCO₂ (“normo”-capnic hypoxia); (2) 50 per cent oxygen with carbon dioxide accumulation (hypercapnia hyperoxia); and (3) carbon dioxide accumulation in room air (hypercapnic hypoxia). The data indicate (1) 15 patients showed no measurable ventilatory response to “normo”-capnic hypoxia and two patients showed blunted responses; (2) seven patients showed no ventilatory responses to carbon dioxide whereas 10 patients showed suboptimal increases; (3) combined hypoxia and hypercapnia caused a suboptimal ventilatory response in four patients. These same four patients showed blunted as opposed to absent ventilatory responses to carbon dioxide. (4) Five patients showed no ventilatory responses to all combinations.These 17 patients together with three others not so extensively studied have been managed by nocturnal diaphragm pacing for periods of four months to nearly eight years.We conclude (1) ablation or severe blunting of the ventilatory responses to hypoxia is a frequent and previously underestimated component of this disorder; and (2) diaphragm pacing is an appropriate form of therapy.     

急性低氧及高二氧化碳刺激对阻塞性睡眠呼吸暂停低通气综合征患者外周动脉硬度及血压的影响

目的 探讨急性低氧及高CO2刺激对OSAHS患者外周动脉硬度和血压的影响.方法 选取2006年1月至12月到北京大学人民医院睡眠中心进行多导睡眠呼吸生理监测者,试验组包含呼吸暂停低通气指数(AHI)≥10次/h的OSAHS患者28例,男22例,女6例,平均年龄(40±14)岁;对照组包含26名AHI<5次/h的健康志愿者,男20名,女6名,平均年龄(40±15)岁,均排除高血压、糖尿病、冠状动脉粥样硬化性心脏病及其他心、肺、血管疾病.两组均按相同方法测定四肢血压及心脏-踝血管指数(CAVI),以清醒平卧休息时为基础值,通过重复呼吸法利用特制的密闭呼吸回路分别进行急性高CO2、低氧、低氧合并高CO2吸入刺激,每次刺激结束后立即重复测定四肢血压及CAVI值.计数资料的对比采用χ2检验,多组间比较采用单因素方差分析,组间两两比较采用t检验.结果 两组间基础状态下收缩压、舒张压、平均压及CAVI值比较差异均无统计学意义(t值分别为1.720、1.891、1.828及0.103,均P>0.05).给予高CO2刺激后两组CAVI均呈下降趋势,但试验组[(7.3±1.2)m/s]下降的程度与基础状态[(7.3±1.3)m/s]比较差异无统计学意义(t=0.333,P>0.05),对照组[(7.0±1.4)m/s]出现明显下降(t=2.587,P<0.05);两组的收缩压均明显升高.给予低氧刺激后两组CAVI均呈升高趋势,试验组[(7.3±1.1)m/s]改变不明显,对照组[(7.6±1.6)m/s]明显升高,差异有统计学意义(t=-3.882,P<0.01),血压没有明显改变(t值分别为-0.434及-0.400,均P>0.05).给予低氧合并高CO2刺激后两组CAVI均呈升高趋势,对照组[(7.5±1.7)m/s]明显升高,但程度较单纯低氧刺激时低,血压的改变与单纯高CO2刺激时类似.结论 CO2升高及低氧均可影响外周动脉硬度.OSAHS患者对低氧和高CO2刺激的反应性明显低于健康对照组.     

Depression of hypoxic and hypercapnic ventilatory drives in severe asthma.

Because of the previous finding of an attenuated hypoxic ventilatory drive in a teenager with severe asthma, the ventilatory responses to hypoxia and hypercapnia were examined during remission in 16 patients with the history of severe asthma. Spirometric and body plethysmographic pulmonary functions were normal or nearly normal just prior to ventilatory drive testing. The ventilatory responses to progressive isocapnic hypoxia and to hyperoxic hypercapnia were studied. Both hypoxic and hypercapnic drives were significantly depressed in the asthmatic patients. Factors known to blunt the ventilatory drives were not present in this group of patients. Hence, the etiology of these changes is unclear. In some patients, these depressed respiratory drives might contribute to hypoventilation, to severe hypoxemia, and to respiratory failure during severe asthma.     

Decreased sensitivity to alpha-adrenergic stimulation in hypothyroid patients

Nine hypothyroid patients had blood pressure and pulse rate responses to the alpha-adrenergic agonist phenylephrine measured before [T4 index, 45.045 +/- 9.009 nmol/L (mean +/- SEM); TSH, 57.1 +/- 23.6 mU/L] and after 4 +/- 0.5 months of thyroid replacement therapy (T4 index, 141.570 +/- 29.601 nmol/L; TSH, 2.6 +/- 1.0 mU/L). Hypothyroid patients had a smaller blood pressure increment and heart rate decrement at both 66.7 and 100 micrograms/min infusion rates of phenylephrine. Furthermore, the slope of the dose-response curves for systolic (2.06 +/- 0.22 vs. 1.32 +/- 0.19; P less than 0.01) and diastolic (1.04 +/- 0.18 vs. 0.62 +/- 0.08; P less than 0.01) blood pressures were significantly greater after thyroid replacement therapy. Pulse rate changes remained proportional to blood pressure changes in hypothyroid patients, so there was no change in baroreflex sensitivity. Plasma norepinephrine levels were higher before than after thyroid replacement (2.41 +/- 0.28 vs. 1.82 +/- 0.29 nmol/L, respectively; P less than 0.01). Thus, hypothyroid patients have diminished pressor sensitivity to an alpha-adrenergic agonist and increased plasma levels of the alpha-adrenergic neutrotransmitter norepinephrine.     

Longitudinal analyses of respiratory chemosensitivity in normal subjects

To evaluate relative contributions of inherent versus extrinsic factors to respiratory chemosensitivity, ventilatory responses to isocapnic progressive hypoxia and normoxic progressive hypercapnia were examined at intervals of 8 to 10 yr in 32 healthy male volunteers aged 42.2 +/- 1.4 yr (SEM) in the final examination. The volunteers included 22 sons of patients with chronic obstructive pulmonary disease. The mean value for the slope factor of the end-tidal PO2-ventilation hyperbola (A) significantly decreased from 98.3 +/- 12.2 to 77.4 +/- 10.3 L/min mm Hg (p less than 0.05), but that for the end-tidal PCO2 ventilation line (S) did not change over the years. The individual values for the hypoxic ventilatory response were significantly correlated (r = 0.63, p less than 0.001) between the initial and final examinations but not so for the hypercapnic ventilatory response (r = 0.23, NS), suggesting that the latter is more subject to influence from extrinsic factors than the former in the long term. The reproducibility of both tests expressed as coefficients of variation was similar or rather small for the hypercapnic ventilatory response, which was determined by three consecutive measurements at 1 wk intervals in a different group of six subjects. From these data we conclude that hypoxic chemosensitivity is more determined by factors inherent to the individual than hypercapnic chemosensitivity and that it is more systematically influenced by temporal factors, as demonstrated by the systematic decrease over the years.     

Hypoxic and hypercapnic ventilatory responses in awake children with congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS) has been thought to be a disorder of central chemoreceptor responsiveness. Previous studies in CCHS have shown decreased or absent ventilatory responsiveness to both hypercarbia and hypoxia. However, hypoxic responsiveness during wakefulness has not been systematically studied. We studied hypoxic and hypercapnic ventilatory responses during wakefulness in five children with CCHS (6 to 11 yr of age). To measure the hypercapnic response, the children rebreathed a hyperoxic hypercapnic mixture until PaCO2 reached 56 to 69 mm Hg. For the hypoxic response, the children rebreathed a hypoxic gas mixture, at mixed venous PCO2, until SaO2 had fallen to less than 78%. We found that the ventilatory responses to hypercapnia and hypoxia were very variable (linear correlation coefficients ranging from -0.44 to +0.63 for hypercapnic responses and from -0.15 to +0.77 for hypoxic responses), with no significant change from baseline in response to either stimulus. There was no evidence of progressive ventilatory stimulation despite increasing stimulus. Additionally, these children had no subjective sensation of dyspnea or discomfort. This establishes that hypoxic and hypercapnic ventilatory control is absent during wakefulness. Chemoreceptor control (peripheral and central) is, therefore, defective in all states in children with CCHS. We speculate that the defect in CCHS lies in central integration of the central and peripheral chemoreceptor signals.     

Effect of unilateral pulmonary vagotomy on respiratory control in man

We studied the breathing pattern and pulmonary function at rest, and ventilatory responses to progressive hypoxia and hypercapnia in 7 awake patients who had undergone esophageal-carcinoma resection with sectioning of the right pulmonary vagal branch by lymphadenectomy. Twelve control patients, who had received the same surgery without vagotomy, were also studied by the same protocol. Two months after the operation, both patient groups demonstrated substantial depressions in FVC and FEV1.0, and slight augmentations in breathing frequency, minute ventilation, and occlusion pressure at 0.2s (P0.2) at rest. In the vagotomized group, the occlusion pressure responses to hypercapnia (delta P0.2/delta PaCO2) and hypoxia (delta P0.2/delta SaO2) in terms of response curve slope increased from 1.3 +/- 1.2 to 1.9 +/- 1.1 cm H2O/Torr and from 0.29 +/- 0.19 to 0.88 +/- 0.53 cm H2O/% (p less than 0.05), respectively. Contrary to the vagotomized patients, the nonvagotomized control group exhibited no significant changes in ventilatory chemosensitivities. Furthermore, when comparing the control and vagotomized groups, postoperative ventilatory chemosensitivity responses in terms of both hypercapnic and hypoxic occlusion pressure responses were significantly higher in the latter. We suggest that (1) due to the development of the substantial mechanical limitation in pulmonary functions, the Hering-Breuer inflation reflex became activated after surgery, and (2) a diminished Hering-Breuer reflex effect to inhibit the respiratory centers by unilateral vagotomy may have resulted in augmented ventilatory chemosensitivities.     

Hypercapnic ventilatory response in recipients of double-lung transplants.

Ten survivors of double lung transplantation using a tracheal anastomosis underwent assessment of their ventilatory responses to hypercapnia (HCVR) at least 3 months postsurgery. At the time of HCVR testing, pulmonary functions were normal in four and abnormal in six patients who demonstrated degrees of obstruction, restriction, or mixed defects. Arterial blood gas measurements were normal. Postoperatively, hypercapnic responses were low or low normal. Mean changes in tidal volume and mean change in respiratory frequency in response to hypercapnia postoperatively were not different in patients with normocapnic versus hypercapnic preoperative blood gases. Neither postoperative resting PCO2 nor muscle strength (as measured by MIP) were predictive of the degree or character of the patients' ventilatory responses to hypercapnia. The factors resulting in the observed blunting of the hypercapnic response in this denervated population require further clarification; however, comparison of data between this patient population and recipients of heart-lung transplantation reported elsewhere suggests that alterations in pulmonary function correlate with the observed depression in HCVR.     

Blunted growth hormone (GH) responsiveness to GH-releasing hormone in obese patients: influence of prolonged administration of the serotoninergic drug fenfluramine

The aim of the present study was to ascertain if reduced central serotoninergic activity might contribute to the well-known blunted growth hormone (GH) response to GH-releasing hormone (GHRH) in obese patients. Thus, we studied the effect of prolonged stimulation of the serotoninergic system by fenfluramine (FF; 60 mg twice daily for 7 days) on GHRH-induced GH release in nine obese and seven normal subjects. In controls, GHRH (100 micrograms intravenously [IV]) injection increased GH levels from 2.3 +/- 1.8 (+/- SE) to 18.5 +/- 2.8 mU/L, P less than .002. FF administration enhanced both basal and GHRH-stimulated GH levels (peak, 38.4 +/- 8.3 v 6.9 +/- 2.6 mU/L, P less than .002). This response was significantly higher (P less than .02) than in pretreatment. In obese patients, GH responsiveness to GHRH was slight (peak, 7.1 +/- 2.0 v 0.6 +/- 0.18 mU/L, P less than .01) and lower (P less than .01) than in controls. FF administration did not affect this response. In controls, the enhanced FF-induced GH release after a maximal dose of GHRH indicates that serotoninergic activation influences GH secretion and that the mechanism involved is independent of endogenous GHRH. In obese patients, we found a blunted GH responsiveness to GHRH that was not affected by FF, thus supporting the hypothesis that the serotoninergic control on GH release is impaired.     

Abnormal breathing during sleep and chemical control of breathing during wakefulness in patients with sleep apnea syndrome

The possible role of ventilatory control in relation to sleep apnea has not yet been clarified. We investigated the relationship between awake ventilatory drives to hypoxia and hypercapnia and sleep-disordered breathing in 21 subjects with sleep apnea syndrome. The awake hypoxic ventilatory drive, which was evaluated by occlusion pressure responses, was inversely correlated with the magnitude of maximal oxygen desaturation during sleep as well as the ratio of duration with more than 4 and 10% oxygen desaturation to total sleep time. On the other hand, the awake hypercapnic ventilatory drive was not correlated with these parameters of sleep desaturation. Apnea index and duration were not correlated with the degree of hypoxic or hypercapnic ventilatory drive, respectively. Our study concluded that sleep desaturation is better correlated with hypoxic ventilatory drive than with hypercapnic ventilatory drive in patients with sleep apnea syndrome. These results are different from the results obtained in the patients with COPD in our previous study.     

Flurazepam attenuates the arousal response to CO2 during sleep in normal subjects

Increased episodes and duration of apnea during sleep associated with arterial oxygen desaturation have been reported after administration of flurazepam. We postulated that an alteration in respiratory control during sleep might be the underlying mechanism of this observation. Accordingly, we measured isocapnic hypoxic and hyperoxic hypercapnic ventilatory and arousal responses during natural (NS) and during flurazepam-induced (FS) sleep. We found no significant difference in the ventilatory response to hypoxia during FS compared with that during NS in 8 normal subjects. Similarly, although the ventilatory response to hypercapnia was performed in only 4 of the 8 subjects during FS, no significant difference from that during NS was noted in these subjects. There was, however, a significant decrease in the number of hypercapnic response tests in which arousal occurred after flurazepam administration (85% in NS versus 54% in FS; p less than 0.005). Additionally, an increase was seen in the mean PACO2 level at which arousal occurred during FS (51 +/- 1.6, means +/- SEM) as compared with that during NS (49 +/- 0.9; p less than 0.07). A similar but not significant decrease was noted in the number of hypoxic response tests in which arousal occurred (28% during NS versus 17% during FS). We conclude that while ventilatory responses to hypoxia and hypercapnia are normal during sleep after flurazepam administration, a decrease in arousal response is seen after administration of this drug in normal subjects. This alteration in arousal response may be the pathogenic mechanism of the increased duration of apnea reported in association with flurazepam.     

Hypothyroidism and cognition: preliminary evidence for a specific defect in memory.

The effect(s) of hypothyroidism on adult brain cognitive function are poorly understood. We performed a series of neuropsychological tests in 13 thyroid cancer patients while they continued to take their usual dose of levothyroxine (LT4) and again after discontinuing thyroid hormone. Three euthyroid subjects were also tested twice to assess the effect of repeated testing on performance. The tests assessed memory, mood, and attentional resources and controlled for the practice effects of repeated testing. The mean thyrotropin (TSH) on LT4 was 0.56 +/- 0.76 mU/L and while hypothyroid was 69 +/- 33 mU/L. While hypothyroid, the mean Beck depression score was significantly higher (15.31 +/- 9.41 hypothyroid vs. 7.31 +/- 4.82 on LT4) and the subjects rated themselves worse relative to functional memory, concentration, thinking, alertness, and motivation. Hypothyroidism was associated with a decrease in retrieval from memory (p = 0.0034), and this effect could not be attributed to depression or to practice effects. Thyroid state did not affect immediate recall, verbal learning, inhibitory efficiency, information processing speed, or attention switching. Athyrosis is associated with a decrement in delayed recall of verbal information but not in other objective measures of cognition, suggesting that the memory decrement of hypothyroidism is not caused by a generalized reduction in attentional resources.     

Sleep deprivation and the control of ventilation

Sleep deprivation is common in acutely ill patients because of their underlying disease and can be compounded by aggressive medical care. While sleep deprivation has been shown to produce a number of psychological and physiologic events, the effects on respiration have been minimally evaluated. We therefore studied resting ventilation and ventilatory responses to hypoxia and hypercapnia before and after 24 h of sleeplessness in 13 healthy men. Hypoxic ventilatory responses (HVR) were measured during progressive isocapnic hypoxia, and hypercapnic ventilatory responses (HCVR) were measured using a rebreathing technique. Measures of resting ventilation, i.e., minute ventilation, tidal volume, arterial oxygen saturation, and end-tidal gas concentrations, did not change with short-term sleep deprivation. Both HVR and HCVR, however, decreased significantly after a single night without sleep. The mean hypoxic response decreased 29% from a slope of 1.20 +/- 0.22 (SEM) to 0.85 +/- 0.15 L/min/% saturation (p less than 0.02), and the slope of the HCVR decreased 24% from 2.07 +/- 0.17 to 1.57 +/- 0.15 L/min/mmHg PCO2 (p less than 0.01). These data indicate that ventilatory chemosensitivity may be substantially attenuated by even short-term sleep deprivation. This absence of sleep could therefore contribute to hypoventilation in acutely ill patients.