Central sleep apnea.

Neurophysiologically, central apnea is due to a temporary failure in the pontomedullary pacemaker generating breathing rhythm. As a polysomnographic finding, central apneas occur in many pathophysiological conditions. Depending on the cause or mechanism, central apneas may not be clinically significant, for example, those that occur normally at sleep onset. In contrast, central apneas occur in a number of disorders and result in pathophysiological consequences. Central apneas occur commonly in high-altitude sojourn, disrupt sleep, and cause desaturation. Central sleep apnea also occurs in number of disorders across all age groups and both genders. Common causes of central sleep apnea in adults are congestive heart failure and chronic use of opioids to treat pain. Under such circumstances, diagnosis and treatment of central sleep apnea may improve quality of life, morbidity, and perhaps mortality. The mechanisms of central sleep apnea have been best studied in congestive heart failure and hypoxic conditions when there is increased CO2 sensitivity below eupnea resulting in lowering eupneic PCO2 below apneic threshold causing cessation of breathing until the PCO2 rises above the apneic threshold when breathing resumes. In many other disorders, the mechanism of central sleep apnea (CSA) remains to be investigated.

Central sleep apnea.

Central apnea is caused by temporary failure in the pontomedullary pacemaker generating breathing rhythm, which results in the loss of ventilatory effort, and if it lasts 10 seconds or more it is defined as central apnea. This article reviews current knowledge on central sleep apnea.

Acute generalized exanthematous pustulosis due to thallium.

Acute generalized exanthematous pustulosis (AGEP) is characterized clinically by fever, pruritus and acute pustular eruption. Usually a drug is found to be the responsible agent. We present a patient who experienced an acute generalized exanthematous pustulosis due to radioactive thallium. The eruption cleared rapidly after discontinuation of the drug and systemic corticosteroid therapy.

Lymphangioma circumscriptum of the penis mimicking venereal lesions.

Lymphangioma circumscriptum (LC) involving the penis is rare. We report two patients with penile LC. The lesions developed in early infancy in one patient, and during puberty in the other. The lesions resembled molluscum contagiosum in one and genital warts in the other. The first patient was previously treated with a diagnosis of venereal disease. A literature search found only 4 LC patients with penile lesions reported in the English literature. These cases are presented for their rarity, and to increase diagnostic vigilance and desirability of non-intervention.

Safety and efficacy of glycolic acid facial peel in Indian women with melasma.

BACKGROUND: Melasma is a common disorder of facial hyperpigmentation. Many modalities of treatment are available, but none is satisfactory. MATERIALS AND METHODS: Twenty-five nonpregnant female patients with a minimum melasma area and severity index (MASI) of 15 were recruited in the study. After a detailed history and clinical examination under natural light and Wood's light, MASI was calculated and color photographs were taken of all patients. Patients were advised to carry out a prepeel program of daily application of topical sunscreens (sun protection factor-15, SPF-15) and 10% glycolic acid lotion at night for 2 weeks. Patients were then treated with 50% glycolic acid facial peel once per month for three consecutive months. At regular intervals and at the end of the follow-up period (3 months) after the last peel, the degree of improvement in pigmentation was assessed by remeasuring MASI. Side-effects, if any, were also recorded. The data obtained were statistically analyzed using Student's paired t-test and Spearman rank correlation coefficient test. RESULTS: Improvement in melasma (reduction in MASI) was observed in 91% of patients (P < 0.01). Patients with epidermal-type melasma demonstrated a better response to treatment than those with mixed-type melasma (P < 0.05). CONCLUSIONS: The prepeel program followed by 50% glycolic acid facial peel once per month for three consecutive months proved to be an effective treatment modality in Indian patients without any significant side-effects.

Treatment of central sleep apnea in heart failure.

Recent studies show that central sleep apnea occur in about 40% of patients with heart failure and systolic dysfunction. The pathophysiological consequences of central sleep apnea may contribute to morbidity and mortality of heart failure. Three treatment modalities, oxygen, continuous positive airway pressure and theophylline have been shown to decrease periodic breathing modestly with considerable improvement in arterial oxyhemoglobin desaturation, and variable effects on sleep characteristics. However, long-term effects of central sleep apnea and its treatment on the natural history of heart failure remain to be determined.

Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure.

BACKGROUND: Patients with heart failure and systolic dysfunction may develop disordered breathing during sleep. Repeated episodes of apnea and hypopnea may result in desaturation and arousals, which could adversely affect left ventricular function. The purpose of this study was to determine the short-term effects of continuous positive airway pressure (CPAP) on sleep-disordered breathing and its consequences in heart failure patients. METHODS AND RESULTS: The author prospectively studied 29 male patients whose initial polysomnograms showed 15 or more episodes of apnea and hypopnea per hour (apnea-hypopnea index, AHI). Twenty-one patients had predominately central and 8 patients obstructive sleep apnea. All were treated with CPAP during the subsequent night. In 16 patients, CPAP resulted in virtual elimination of disordered breathing. In these patients, the mean AHI (36+/-12 [SD] versus 4+/-3 per hour, P=0.0001), arousal index due to disordered breathing (16+/-9 versus 2+/-2 per hour, P=0.0001), and percent of total sleep time below saturation of 90% (20+/-23% to 0.3+/-0.7%, P=0.0001) decreased, and lowest saturation (76+/-8% versus 90+/-3%, P=0.0001) increased with CPAP. In 13 patients who did not respond to CPAP, these values did not change significantly. In patients whose sleep apnea responded to CPAP, the number of hourly episodes of nocturnal premature ventricular contractions (66+/-117 versus 18+/-20, P=0.055) and couplets (3.2+/-6 versus 0.2+/-0.21, P=0.031) decreased. In contrast, in patients whose sleep apnea did not respond to CPAP, ventricular arrhythmias did not change significantly. CONCLUSIONS: In 55% of patients with heart failure and sleep apnea, first-night nasal CPAP eliminates disordered breathing and reduces ventricular irritability.

A mechanism of central sleep apnea in patients with heart failure.

BACKGROUND: Breathing is controlled by a negative-feedback system in which an increase in the partial pressure of arterial carbon dioxide stimulates breathing and a decrease inhibits it. Although enhanced sensitivity to carbon dioxide helps maintain the partial pressure of arterial carbon dioxide within a narrow range during waking hours, in some persons a large hyperventilatory response during sleep may lower the value below the apneic threshold, thereby resulting in central apnea. I tested the hypothesis that enhanced sensitivity to carbon dioxide contributes to the development of central sleep apnea in some patients with heart failure. METHODS: This prospective study included 20 men who had treated, stable heart failure with left ventricular systolic dysfunction. Ten had central sleep apnea, and 10 did not. The patients underwent polysomnography and studies of their ventilatory response to carbon dioxide. RESULTS: Patients who met the criteria for central sleep apnea had significantly more episodes of central apnea per hour than those without central sleep apnea (mean [+/-SD], 35+/-24 vs. 0.5+/-1.0 episodes per hour). Those with sleep apnea also had a significantly larger ventilatory response to carbon dioxide than those without central sleep apnea (5.1+/-3.1 vs. 2.1+/-1.0 liters per minute per millimeter of mercury, P=0.007), and there was a significant positive correlation between ventilatory response and the number of episodes of apnea and hypopnea per hour during sleep (r=0.6, P=0.01). CONCLUSIONS: Enhanced sensitivity to carbon dioxide may predispose some patients with heart failure to the development of central sleep apnea.

Effects of nasal O2 on sleep-related disordered breathing in ambulatory patients with stable heart failure.

OBJECTIVE: The purpose of this study was 1) to determine the effects of nasal O2 on periodic breathing, arterial oxyhemoglobin desaturation and nocturnal ventricular arrhythmias in patients with heart failure and 2) determine the characteristics of patients whose periodic breathing will be reversed by O2 administration; our hypothesis was that patients with more severe periodic breathing and desaturation, will respond more favorably to oxygen. DESIGN: Prospective study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs Medical Center. PARTICIPANTS: 36 ambulatory male patients with heart failure whose initial polysomnograms showed periodic breathing with fifteen or more episodes of apnea (A) and hypopnea (H) per hour (AH index, AHI) were treated with nasal O2 during the subsequent full night polysomnography. INTERVENTIONS: Oxygen. MEASUREMENTS AND RESULTS: Arterial blood gases and hydrogen ion concentrations were measured, and cardiac radionuclide ventriculography, Holter monitoring, and polysomnography were done. The studies were scored blindly. Treatment with O2 resulted in a significant reduction in AHI (49+/-19 vs 29+/-29, means+/-SD), central apnea index (28+/-23 vs 13+/-18 per hour), and the percent of total sleep time below an arterial oxyhemoglobin saturation of 90% (23+/-21% vs 0.8+/-2.3%). In spite of virtual normalization of saturation with O2 therapy, the number of ventricular arrhythmias during sleep did not change significantly. In 39% of the patients (14 out of 36), O2 therapy resulted in reversal of central sleep apnea (defined by a reduction in AHI to less than 15/hr). In this group, the AHI decreased by 78% which was significantly (p=0.0001) more than improved (22%) in AHI of the remaining patients (n=22). The main differences between baseline characteristics of the two groups was a significantly higher mean PaCO2 in patients who did respond fully to O2 (39.3+/-5.4 vs 36.1+/-4.2 mm Hg, p=0.03). In both groups, however, O2 administration resulted in significant and similar improvement in arterial oxyhemoglobin saturation (saturation <90%, percent total sleep time 0.1+/-0.3% vs 1+/-3%). CONCLUSION: In patients with stable heart failure, administration of nasal O2 significantly improves periodic breathing and virtually eliminates clinically significant arterial oxyhemoglobin desaturation. The beneficial effects of O2, however, may be modulated by the level of arterial PCO2. Acute O2 therapy has important benefits on sleep apnea and nocturnal arterial oxyhemoglobin desaturation in heart failure patients. Long term benefits of O2 therapy in heart failure and sleep apnea need to be determined.

Ethanol is a potent inhibitor of canine cerebrospinal fluid production: an acute and reversible effect.

Neuropathological studies have shown increased cerebral spaces in alcoholics, yet, the effect of ethanol on cerebrospinal fluid (CSF) production is not known. We investigated the effects of ethanol on CSF production measured by ventriculocisternal perfusion (VCP) technique, in two groups (n=10 in each) of anesthetized, paralyzed and mechanically ventilated dogs. In group I, which served as control, VCP was performed with normal mock CSF. Ethanol (150 mg/dl of mock CSF, approximately 33 mM) was added to VCP in group II. Beginning 60 min after the start of VCP, CSF production was measured every 15 min for the next 4 h. In group I, mean (+/-S.D.) value for CSF production was 51+/-10 microliter/min initially and decreased significantly but slightly with time, to the lowest value of 44+/-11 microliter/min at the end of the experiment. In group II, values for CSF production were 41+/-8, 41+/-8, 41+/-8, 43+/-6, 43+/-8, 42+/-6, 42+/-8, 38+/-6, 37+/-6, 36+/-5, 36+/-5, microliter/min, respectively, from 15 to 165 min. These values were invariably significantly lower than their respective mean values in the control group. Furthermore, when ethanol was withdrawn at the trough of CSF production (at 165 min), production significantly increased by about 40%. We conclude that ethanol at a concentration of 150 mg/dl (far below lethal levels) is one of the most potent inhibitory drugs for decreasing CSF production. This effect is short-onset and is fully reversible within 15 min of ethanol withdrawal.

Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations.

BACKGROUND: Heart failure is a highly prevalent disorder that continues to be associated with repeated hospitalizations, high morbidity, and high mortality. Sleep-related breathing disorders with repetitive episodes of asphyxia may adversely affect heart function. The main aims of this study were to determine the prevalence, consequences, and differences in various sleep-related breathing disorders in ambulatory male patients with stable heart failure. METHODS AND RESULTS: This article reports the results of a prospective study of 81 of 92 eligible patients with heart failure and a left ventricular ejection fraction < 45%. There were 40 patients without (hourly rate of apnea/hypopnea, 4 +/- 4; group 1) and 41 patients with (51% of all patients; hourly rate of apnea/hypopnea, 44 +/- 19; group 2) sleep apnea. Sleep disruption and arterial oxyhemoglobin desaturation were significantly more severe and the prevalence of atrial fibrillation (22% versus 5%) and ventricular arrhythmias were greater in group 2 than in group 1. Forty percent of all patients had central sleep apnea, and 11% had obstructive sleep apnea. The latter patients had significantly greater mean body weight (112 +/- 30 versus 75 +/- 16 kg) and prevalence of habitual snoring (78% versus 28%). However, the hourly rate of episodes of apnea and hypopnea (36 +/- 10 versus 47 +/- 21), episodes of arousal (20 +/- 14 versus 23 +/- 11), and desaturation (lowest saturation, 72 +/- 11% versus 78 +/- 12%) were similar in patients with these different types of apnea. CONCLUSIONS: Fifty-one percent of male patients with stable heart failure suffer from sleep-related breathing disorders: 40% from central and 11% from obstructive sleep apnea. Both obstructive and central types of sleep apnea result in sleep disruption and arterial oxyhemoglobin desaturation. Patients with sleep apnea have a high prevalence of atrial fibrillation and ventricular arrhythmias.

Association of low PaCO2 with central sleep apnea and ventricular arrhythmias in ambulatory patients with stable heart failure.

BACKGROUND: Central sleep apnea frequently occurs in patients with heart failure. Because it is not practical to perform sleep studies on all patients, readily available laboratory tests that predict sleep apnea would be clinically useful. Arterial PCO2 has a profound influence on breathing during sleep: When it decreases below a certain threshold, apnea occurs. OBJECTIVE: To study the value of a low PaCO2 while patients are awake in predicting central sleep apnea in patients with stable, treated heart failure. DESIGN: Prospective study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs Medical Center. PARTICIPANTS: 59 patients with left ventricular ejection fractions of 45% or less. MEASUREMENTS: Arterial blood gases and hydrogen ion concentrations were measured, and cardiac radionuclide ventriculography, Holter monitoring, and polysomnography were done. RESULTS: Patients were classified as eucapnic (PaCO2 > 35 and < 44 mm Hg [n = 41]) or hypocapnic (PaCO2 < or = 35 mm Hg [n = 18]). The mean (+/- SD) hourly episodes of apnea or hypopnea (36 +/- 25 and 20 +/- 27; P = 0.015), the prevalence of central sleep apnea (78% and 39%; P = 0.01), and the mean hourly occurrences of ventricular tachycardia (2 +/- 3 and 0.1 +/- 0.1; P = 0.003) were significantly greater in hypocapnic patients than in eucapnic patients. CONCLUSION: Data on patients with heart failure in this study are consistent with the physiologic notion that a low PaCO2 results in ventilatory instability and central apnea during sleep. The positive predictive value of a low PaCO2 for central sleep apnea is 78%. The prevalence of ventricular tachycardia was 20 times greater in hypocapnic patients than in eucapnic patients.

Sentinel node excision for the diagnosis of metastatic neuroendocrine carcinoma of the skin: a case report.

The technology of sentinel node lymphoscintigraphy has made it possible to map and identify the lymph nodes draining the site of a primary cutaneous malignancy. This technique is now being used in the treatment of melanoma, and breast and vulvar carcinoma. With melanoma and breast carcinoma, the histology of the sentinel lymph node (SLN) has been found to be reflective of the histology of the remainder of the nodal basin. The concept of sampling the SLN is to provide an accurate staging for the entire nodal basin, obviating the need for a complete lymphadenectomy if the SLN is negative. It is believed that cutaneous malignancies with a propensity for regional metastasis, such as neuroendocrine carcinoma of the skin, may spread via a similar lymphatic pathway involving an SLN. Using this technique we identified and excised the SLNs in a patient with a neuroendocrine carcinoma of the skin that contained the only focus of metastatic disease. Although this technique is still investigational we believe it holds great promise in being able to detect occult metastatic nodal disease in clinically node-negative patients.

The use of selective lymphadenectomy in squamous cell carcinoma of the wrist: a case report.

Squamous cell carcinoma is the second most common skin cancer in humans and has a rate of metastasis of 0.5%-5.9%. Regional lymphadenectomy is generally not recommended for patients with advanced lesions and clinically node-negative disease. Selective lymphadenectomy using preoperative lymphoscintigraphy and intraoperative radiolymphoscintigraphy and vital dye injections to identify the sentinel lymph node may help in staging patients with upper-extremity squamous cell carcinoma while avoiding the complications of a complete axillary node dissection. The case of a patient with a large squamous cell carcinoma of the wrist with clinically negative findings on axillary examination who was found to have a sentinel lymph node containing metastatic tumor is presented. Although this treatment method is still considered investigational, it holds great promise for nodal staging by being able to detect occult metastatic nodal disease in otherwise clinically node-negative patients.

Different effects of omeprazole and Sch 28080 on canine cerebrospinal fluid production.

We investigated the effects of omeprazole and Sch 28080, a more specific and a more potent inhibitor of K+,H+-ATPase than omeprazole, in canine cerebrospinal fluid (CSF) production. CSF production was measured by ventriculocisternal perfusion (VCP) technique in three groups (n = 10 in each group) of anesthetized, paralyzed and mechanically ventilated dogs. Group I served as control, Sch 28080 (10(-4) mol/l of synthetic CSF) was added to VCP in group II, and omeprazole (10(-5) mol/l of synthetic CSF) was added to VCP in group III, after baseline control CSF production had been determined at 15, 30, 45, and 60 min. Comparing the three groups, the mean baseline values for CSF production did not differ significantly. However, the percent decreases in CSF production in the omeprazole treated group were 26 +/- 17 and 24 +/- 13 at 210 and 225 min, which were significantly more than the respective values in the control group. Percent decrease in CSF production in Sch 28080 was not significantly different from that in the control group. We conclude that in the canine model, physiological doses of omeprazole decrease CSF production by about 26%. However, the effect is independent of the K+,H+-ATPase activity, since Sch 28080 which is more potent than omeprazole did not significantly affect CSF production.

Central sleep apnea-hypopnea syndrome in heart failure: prevalence, impact, and treatment.

Despite recent advances in its treatment, congestive heart failure associated with depressed left ventricular function continues to be associated with excess morbidity and mortality. Multiple factors may contribute to the progressively declining course of heart failure. Nocturnal arterial oxyhemoglobin desaturation caused by sleep-disordered breathing could be a contributing factor, particularly because it has been associated with excess mortality in patients with chronic obstructive pulmonary disease. Cheyne and Stokes were the first to observe periodic breathing in patients with heart failure (Cheyne-Stokes respiration). However, relatively large-scale systematic studies have been performed only recently. We studied 42 patients with stable, optimally treated heart failure, without other co-morbid disorders: 19 patients (45%) had an apnea-hypopnea index of more than 20/hour. These episodes were associated with an excess number of arousals and arterial oxyhemoglobin desaturation. Treatment options include nocturnal administration of oxygen, continuous positive airway pressure (CPAP), and medications such as theophylline. Large-scale studies are needed to evaluate the efficacy of these treatment options on quality of life, morbidity, and mortality of patients with heart failure.

Effect of theophylline on sleep-disordered breathing in heart failure.

BACKGROUND: Theophylline has been used to treat central apnea associated with Cheyne-Stokes respiration (periodic breathing). We studied the effect of short-term oral theophylline therapy on periodic breathing associated with stable heart failure due to systolic dysfunction. METHODS: Fifteen men with compensated heart failure (left ventricular ejection fraction, 45 percent or less) participated in the study. Their base-line polysomnograms showed periodic breathing, with more than 10 episodes of apnea and hypopnea per hour. In a double-blind crossover study, the patients received theophylline or placebo orally twice daily for five days, with one week of washout between the two periods. RESULTS: After five days of treatment, the mean (+/-SD) plasma theophylline concentration was 11 +/- 2 microgram per milliliter. Theophylline therapy resulted in significant decreases in the number of episodes of apnea and hypopnea per hour (18 +/- 17, vs. 37 +/- 23 with placebo and 47 +/- 21 at base line; P<0.001), the number of episodes of central apnea per hour (6 +/- 14, vs. 26 +/- 21 and 26 +/- 20, respectively; P<0.001), and the percentage of total sleep time during which the arterial oxyhemoglobin saturation was less than 90 percent (6 +/- 11 percent, vs., 23 +/- 37 and 14 +/- 14 percent, respectively; P<0.04). There were no significant differences in the characteristics of sleep, the frequency of ventricular arrhythmias, daytime arterial-blood gas values, or the left ventricular ejection fraction during the base-line, placebo, and theophylline phases of the study. CONCLUSIONS: In patients with stable heart failure, oral theophylline therapy reduced the number of episodes of apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during sleep.

Occult sleep-disordered breathing in stable congestive heart failure.

OBJECTIVE: To determine the prevalence and effect of sleep-disordered breathing in ambulatory patients with stable, optimally treated congestive heart failure. DESIGN: A prospective, longitudinal study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs medical center. PATIENTS: 42 of the 48 eligible patients with stable congestive heart failure and left ventricular systolic dysfunction (left ventricular ejection fraction < or = 45%). MEASUREMENTS: After an adaptation night, polysomnography and Holter monitoring were done in the sleep laboratory. Arterial blood gases and pH were measured, and cardiac radionuclide ventriculography and pulmonary, renal, and thyroid function tests were done. RESULTS: Patients were divided into two groups. Group I (n = 23) had an hourly rate of apnea and hypopnea (apnea-hypopnea index) of 20 episodes per hour or less; group II (n = 19 [45%; CI, 30% to 60%]) had an index of more than 20 episodes per hour. In group II, the index varied from 26.5 to 82.2 episodes per hour (mean +/- SD, 44 +/- 13 episodes per hour; CI, 38 to 51 episodes per hour). Group II had significantly more arousals (24 +/- 12 compared with 3 +/- 3 in group I) that were directly attributable to episodes of apnea and hypopnea, longer periods of time with an arterial oxyhemoglobin saturation of less than 90% (23% +/- 24% of total sleep time compared with 2% +/- 4%), lower arterial oxyhemoglobin saturation during sleep (74% +/- 13% compared with 87% +/- 4%), lower left ventricular ejection fraction (22% +/- 9% compared with 30% +/- 10%), and a significantly increased number of episodes of nocturnal ventricular arrhythmias. Multiple regression analyses showed that left ventricular systolic dysfunction was an independent risk factor for sleep apnea in patients with congestive heart failure. CONCLUSIONS: The prevalence of severe occult sleep-disordered breathing is high in ambulatory patients with stable, optimally treated chronic congestive heart failure. The breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. Severe untreated sleep-disordered breathing may adversely affect left ventricular function, resulting in a vicious cycle that could contribute to death in patients with congestive heart failure. Prospective, longitudinal studies on survival are needed.