Tratamento da respiração de Cheyne-Stokes em pacientes com insuficiência cardíaca congestiva
Escola Paulista de Medicina – UNIFESP - São Paulo, SP
A respiração de Cheyne-Stokes é um evento presente em pacientes cardiopatas e com doença neurológica cerebral. Acomete aproximadamente 40% dos cardiopatas estáveis com fração de ejeção (Fej) menor que 45%1. É um sinal de gravidade da insuficiência cardíaca, por estar associado a um aumento da estimulação simpática, um conhecido fator de mau prognóstico nesses pacientes2. Apesar de poder ser observada durante a vigília, seu diagnóstico é feito por meio de polissonografia e consiste de:
• Pelo menos três ciclos consecutivos de uma alteração crescendo-decrescendo na amplitude respiratória.
• Um ou ambos dos seguintes:
a) Índice de apnéia/hipopnéia central maior ou igual a 5 por hora.
b) A alteração cíclica crescendo-decrescendo da amplitude respiratória tem duração de pelo menos 10 minutos consecutivos3 (
Os mecanismos que levam a respiração de Cheyne-Stokes (RCS) ainda não foram completamente definidos. Sabe-se que esses pacientes são hipocápnicos, o que precipitaria o aparecimento de apnéias centrais. Especulam-se vários motivos para essa hipocapnia/hiperventilação crônica: maior sensibilidade dos quimiorreceptores respiratórios ao CO2; baixos estoques corpóreos de O2 levando a instabilidade respiratória e hiperventilação; edema pulmonar intersticial em razão de alta pressão capilar pulmonar. O aumento do tempo circulatório dos pacientes com insuficiência cardíaca congestiva (ICC) também é implicado na fisiopatologia da RCS, já que o atraso na informação da variação da PaCO2 do pulmão para os quimiorreceptores respiratórios provocaria a oscilação típica desse tipo de respiração4.
Em pesquisa sobre o assunto no Medline, o CPAP é a modalidade mais estudada (40%). Oxigenioterapia compreende 16% das referências. O tratamento da RCS visa combater a hipóxia e os despertares noturnos presentes durante a respiração e que aumentam a atividade simpática; melhorar a sonolência diurna e melhorar a função cardíaca. As modalidades terapêuticas que veremos a seguir tentam atacar um dos prováveis mecanismos geradores da respiração (
O CPAP (Continuous Positive Airway Pressure) já foi extensivamente comprovado como a modalidade terapêutica de escolha na síndrome de apnéia/hipopnéia obstrutiva do sono, na qual tem a função de evitar o colapso das vias aéreas superiores. Entretanto, na RCS o CPAP tem outras funções. Ele aumenta os estoques corpóreos de O25 mediante o incremento da capacidade residual funcional, além de elevar a PaCO2 por diminuir o volume corrente. Ao aumentar os estoques corpóreos de O2, reduz a instabilidade respiratória responsável pelas variações da respiração. A elevação da PaCO2 dificulta o aparecimento de apnéias centrais em razão do aumento da diferença entre o PaCO2 do paciente e o PaCO2 do limiar de apnéia. Krachman demonstrou os efeitos do CPAP nas reservas de O2 corpóreo. CPAP reduziu a velocidade de queda da saturação da oxi-hemoglobina (dSat/dt) provocada pelas apnéias, um valor que se correlaciona negativamente com as reservas corpóreas de O25.
A pressão positiva em vias aéreas também age melhorando a função ventricular nos pacientes com ICC por diminuir a pré e a pós-carga. Naughton demonstrou que o CPAP reduz a pressão transmural de ventrículo esquerdo (PTMVE = pressão sistólica de ventrículo esquerdo – pressão esofágica) e o produto PTMVE sistólica x freqüência cardíaca (um índice de geração de força miocárdica sistólica e consumo de O2) diminuindo a carga do ventrículo esquerdo (VE)6. Foi demonstrado também que os pacientes cardiopatas com RCS têm congestão venosa pulmonar e pressão intersticial elevada7, o que causa aumento da estimulação vagal aferente provocando hiperventilação. O CPAP também combate o edema intersticial.
Pelo fato de que grande parte desses pacientes ronca, o CPAP pode funcionar por diminuir a resistência de vias aéreas. Nos roncadores, há uma queda maior na pressão pleural e, portanto, maior pré-carga de ventrículo esquerdo, o que se corrige tornando as vias aéreas mais pérveas com o CPAP.
Vários estudos mostram os efeitos do CPAP na RCS de pacientes cardiopatas reduzindo o índice de apnéia/hipopnéia (IAH) centrais2,5,8-12, melhorando a saturação da oxi-hemoglobina (SatO2) noturna2,8-10,12, diminuindo o tempo de sono em RCS9 e o número de despertares breves9-12, incrementando assim a porcentagem de sono de ondas lentas9,12. Seus efeitos também se mantêm durante o dia, como observado na melhora da Fej de VE2,11,12, na classificação de ICC da NYHA2,9,11,12, na redução da sonolência diurna na escala de Epworth e queda da freqüência cardíaca durante a vigília11. Diminui a atividade simpática reduzindo a concentração da norepinefrina urinária noturna e a concentração de norepinefrina plasmática matutina2 e diminui a freqüência de arritmias ventriculares10. Aumenta a sobrevida livre de transplante cardíaco e diminui a taxa de mortalidade/transplante cardíaco em trabalho que realizou seguimento por mais de dois anos13. Em relação à qualidade de vida, houve melhora na pontuação do "Chronic Heart Failure Questionaire" nos quesitos dispnéia, fadiga, bem-estar emocional e domínio da doença11.
Nem todos os pacientes respondem ao CPAP. Javaheri10 encontrou uma freqüência de somente 43% de resposta (pacientes cujo IAH decresceu para menos que 15 por hora). Os "não-respondedores" tinham um IAH médio de 62, e os "respondedores", um IAH médio de 36, o que mostra que os pacientes mais graves podem não responder ao CPAP provavelmente porque esse pode levar a uma tendência a despertar, promovendo instabilidade respiratória em razão das pressões mais elevadas usadas nesses pacientes. Outros estudos encontraram uma freqüência maior de resposta, mas tinham uma população menos grave9.
Contrariamente, outros autores mostram falha do CPAP em melhorar a RCS14,15 ou mesmo que esse possa ser deletério para esses pacientes15. Um erro metodológico que pode ter contribuído para o insucesso do CPAP foi o protocolo utilizado no ajuste da pressão, iniciada arbitrariamente em 7,5 cmH2O ou maior. Javaheri10 e Naughton e cols.11 elaboraram maneiras diferentes de titular a pressão correta, mas ambos são unânimes em iniciar a titulação com pressão de 5 cmH2O e aumentar gradualmente a pressão até um valor tolerável pelo paciente, tentando chegar entre 10 e 12 cmH2O. Outra possível explicação para ausência de efeitos benéficos é a avaliação do CPAP após somente uma noite de uso14. Já foi demonstrado que os benefícios do CPAP são conseguidos com o passar do tempo (há aumento da Fej em um e três meses de uso) e o nível de pressão também pode ser otimizado durante o tratamento.
Recentemente, um importante estudo multicêntrico16 envolvendo 258 pacientes avaliou o uso do CPAP em longo prazo (24 meses) em cardiopatas. O resultado, porém, não foi o esperado. Apesar de reduzir o índice de apnéias centrais, aumentar a saturação da oxi-hemoglobina, melhorar a função cardíaca e reduzir os níveis de norepinefrina plasmática, o CPAP falhou em demonstrar benefício na mortalidade e na sobrevida livre de transplante. No início do estudo, a curva de sobrevida livre de transplante favoreceu o grupo controle, mas após 18 meses, passou a favorecer o grupo do CPAP, não havendo diferença estatística no final do estudo. Esses resultados, que não corroboraram expectativas geradas pelos estudos anteriores, podem decorrer do uso mais freqüente de betabloqueador em relação aos mais antigos. A concomitância do uso do CPAP e betabloqueador limitou o potencial para melhorar a função ventricular obtida somente pelo CPAP.
Um efeito adverso indesejável do CPAP é a diminuição do débito cardíaco e conseqüente hipotensão arterial, que pode ser evitada com titulação da pressão a partir de 5 cmH2O e elevação gradual ao longo de dias ou semanas, conforme tolerado pelo paciente. Outra queixa comum é o desconforto causado pela máscara nasal.
Outro método de ventilação com pressão positiva (ventilação assistida com dois níveis de pressão, BiPAP) foi comparado ao CPAP, porém não conferiu nenhuma vantagem sobre este, além do seu custo proibitivo9.
Os principais efeitos do O2 na RCS são: incremento dos estoques corpóreos de O2 prevenindo instabilidade dos gases arteriais e a remoção do estímulo hipóxico para hiperpnéia permitindo que o PaCO2 aumente alargando a diferença entre o PaCO2 do paciente e o PaCO2 do limiar de apnéia17.
Estudos mostram os vários benefícios do O2 na RCS: redução do IAH8,18-22, melhora da SatO2 noturna8,18-22, diminuição do tempo médio de RCS18,21 e dos despertares breves18,20,22, aumento do sono de ondas lentas18,22, redução da freqüência cardíaca durante a noite20. Não modificou sintomas20,21, porém melhorou um parâmetro de função cognitiva: a velocidade de processamento da informação20. Reduziu a ativação simpática demonstrada pela diminuição da excreção urinária noturna de noradrenalina21. Houve aumento do pico de consumo de O2 em teste de exercício com bicicleta20, que é um forte preditor de mortalidade, o que leva a especulações sobre melhora da sobrevida com O2. Krachman e cols.8 compararam O2 com CPAP num estudo prospectivo randomizado com 25 pacientes e concluíram que as duas modalidades são igualmente efetivas, embora nesse estudo tanto o CPAP como o O2 tenham sido usados somente por uma noite. Como já visto, o efeito do CPAP depende de um tempo prolongado de uso.
O fluxo de O2 usado nesses estudos variou de 2 a 4 l/min, e a taxa de resposta ao O2 (porcentagem dos que tiveram o IAH reduzido para menos de 15 por hora) foi de 39%19. Como no caso do CPAP, os "respondedores" foram aqueles com RCS mais leve (menor IAH, dessaturação da oxi-hemoglobina mais leve e PaCO2 maior).
O mecanismo pelo qual a teofilina age é incerto. Sabe-se que é inibidora da fosfodiesterase,mas nas concentrações utilizadas para tratamento da RCS não tem esse efeito inibitório. Em concentrações terapêuticas, compete com a adenosina em alguns de seus receptores. No sistema nervoso central, a adenosina é depressora respiratória e a teofilina, por competir com ela, tem efeito estimulante respiratório, evitando apnéias centrais.
Demonstrou-se que a teofilina reduziu o IAH23,24, melhorou a SatO2 noturna23,24 e diminuiu os despertares breves totais24 e associados a alterações respiratórias23. Não alterou eficiência do sono, estágios do sono23,24, nem Fej de VE23. Também não alterou arritmias ventriculares, sugerindo ser uma opção segura nesses pacientes. É importante saber que Javaheri e cols.23 usaram O2 nos pacientes em razão da dessaturação da oxi-hemoglobina durante os exames, e isso pode ter contribuído para uma alteração nos resultados.
As doses de teofilina utilizadas foram: 200-300 mg/dia (4,3 mg/kg de peso)24 e 3,3 mg/kg de peso, duas vezes ao dia23. Seus defensores justificam seu uso enaltecendo as limitações das outras modalidades terapêuticas: baixa adesão ao CPAP e possibilidade de remoção inadvertida da cânula de O2 durante o sono.
1) Otimização da medicação para ICC: na verdade, essa deveria ser a primeira opção de tratamento, já que é a mais simples. Walsh e cols.22 demonstraram que pacientes com ICC estáveis em uso de apenas furosemida evoluíram com aumento do sono de ondas lentas e sono REM, redução do IAH e dos eventos de dessaturação, além de incremento no CO2 do final da expiração e redução da ventilação-minuto após acréscimo de captopril 75 mg/dia durante um mês. Dark e cols.25 estudaram pacientes que eram internados por descompensação da insuficiência cardíaca, mostrando anormalidades do padrão respiratório (predominantemente apnéias centrais com RCS) em todos eles. Após compensação da ICC durante a internação com diuréticos, vasodilatadores, anti-hipertensivos, antiarrítmicos e inotrópicos positivos foi realizada nova polissonografia com diminuição do IAH e tendência a melhora da SatO2.
2) Marcapasso: o implante de marcapasso esquerdo ou biventricular com modo de desencadeamento atrial26 mostrou redução do IAH, melhora da SatO2 e da qualidade subjetiva do sono, possivelmente por melhora da função cardíaca. Nesse estudo, nenhum paciente tinha indicação convencional de marcapasso.
3) Benzodiazepínicos: a razão para se usar benzodiazepínicos é o efeito de aumento do limiar de despertar, já que esse é decorrente da RCS e pode ser um fator perpetuante do problema, pela hiperventilação e hipocapnia conseqüentes ao despertar. Estudos mostram redução dos despertares breves, mas sem redução significante do IAH nem da SatO2 noturna27,28. Especial atenção deve ser dada ao paciente com apnéias obstrutivas, pois os benzodiazepínicos podem agravá-los.
4) CO2: o uso de CO2 (0,2-1 l/min) misturado com O2 (2l/min) durante o sono já foi estudado mostrando diminuição na duração da RCS e melhora da SatO2, mas piorou a qualidade do sono e aumentou a atividade simpática29. Além disso, a hipercapnia resultante eleva a pós-carga ventricular esquerda e direita. Por esses motivos, não deve ser indicada para pacientes com ICC.
5) Servoventilação adaptativa: essa nova modalidade ventilatória consiste de um variável suporte ventilatório que se adapta dependendo da fase da respiração: maior nos períodos de apnéia e menor nos períodos de hiperventilação. Corrigiu a RCS, reduzindo objetivamente a sonolência diurna, os níveis plasmáticos de BNP (marcador de severidade da insuficiência cardíaca) e a excreção de metadrenalina urinária30. Melhorou qualidade do sono (aumentou tempo total de sono, eficiência do sono, porcentagem de sono REM e de ondas lentas e diminuiu índice de despertares breves), além de reduzir IAH e dessaturações quando comparado com controle. Houve diferenças significativas de alguns desses parâmetros em comparação ao CPAP31.
Apesar de ser a modalidade mais estudada, a utilização do CPAP na RCS ainda é controversa, e a experiência desse tratamento no Brasil ainda é escassa, já que o CPAP não é fornecido gratuitamente e a maioria dos pacientes tem dificuldade de comprá-lo. O O2 é uma opção no caso dos intolerantes ao CPAP, ou que, por outro motivo, não possam usá-lo. Porém, ainda não foi avaliada a sobrevida em longo prazo dessa modalidade terapêutica. Os outros tratamentos citados aqui necessitam de mais estudos. A RCS é um evento freqüente nos cardiopatas e está associada a um pior prognóstico, sendo, assim, importante o diagnóstico e o tratamento corretos.
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Correspondência: Ivan Guerra de Araújo Freitas Rua Dr. Diogo de Faria, 1226/84 04037-004 – São Paulo, SP E-mail:
Artigo recebido em 11/01/06; revisado recebido em 15/08/06; aceito em 09/10/06.
Treatment of Cheyne-Stokes respiration in patients with congestive heart failure
Escola Paulista de Medicina – UNIFESP - São Paulo, SP - Brazil
Cheyne-Stokes respiration is an event observed in patients with cardiopathies and brain/neurological diseases. It affects around 40% of stable cardiopaths with an ejection fraction (EF) < 45%1. It is a sign of heart failure severity, being associated to an increase in the sympathetic stimulation, which is a known poor prognosis factor in these patients2. Although it can be observed during the state of wakefulness, its diagnosis is achieved through polysomnography and consists of:
- At least 03 consecutive cycles of an increasing-decreasing alteration in the respiratory range.
- One or both of the following:
a) Index of central apnea/ hypopnea
b) The increasing-decreasing cyclic alteration of the respiratory range lasts at least 10 consecutive minutes3 (
The mechanisms that lead to Cheyne-Stokes respiration (CSR) have yet to be completely clarified. It is known that these patients are hypocapnic, which would cause the occurrence of central apnea. Several reasons for this chronic hypocapnia/hyperventilation are speculated: a higher sensibility of the respiratory CO2 chemoreceptors; low body oxygen stores, leading to respiratory instability and hyperventilation; interstitial pulmonary edema due to high lung capillary pressure. The increase in the circulatory time of patients with congestive heart failure (CHF) is also implicated in the physiopathology of CSR, as the delayed information of the lung PaCO2 variation to the respiratory chemoreceptors would cause the typical oscillation of this type of respiration4.
A research on the subject at MEDLINE showed that Continuous Positive Airway Pressure (CPAP) is the most studied modality (40%). Oxygen therapy comprises 16% of the References. The treatment of CSR aims at fighting hypoxia and the nocturnal awakenings present during the respiration, which increase the sympathetic activity, as well as improving diurnal somnolence and heart function. The therapeutic modalities that will be shown subsequently try to attack one of the probable mechanisms that generate the respiration (
The CPAP has been extensively shown as the therapeutic modality of choice in Sleep Obstructive Apnea/Hypopnea Syndrome, where it has the function of preventing the collapse of the upper airways. However, in CSR, CPAP has other functions. It increases the body oxygen stores5 through the increment of the functional residual capacity, in addition to increasing PaCO2 by decreasing the current volume. By increasing the body oxygen stores of, it reduces the respiratory instability, which is responsible for the respiration variations. The elevation of PaCO2 impairs the occurrence of central apneas due to the increase in the difference between the patient’s PaCO2 and the PaCO2 of the apnea threshold. Krachman demonstrated the effects of the CPAP on body stores of O2. CPAP diminished the velocity of the oxyhemoglobin saturation decline (dSat/dt) caused by the apneas, a value that correlates negatively with the body oxygen stores5.
The positive pressure in the airways also acts by improving the ventricular function in patients with CHF by decreasing the pre- and post-load.
Naughton demonstrated that CPAP reduces the left ventricle (LV) end-systolic transmural pressure (LVESTMP = systolic pressure of the left ventricle – esophageal pressure) and the product LVESTMP x cardiac frequency (an index of systolic myocardial power generation and O2 consumption), decreasing the LV load6. It has also been demonstrated that cardiopath patients with CSR have elevated pulmonary venous congestion and interstitial pressure7, which causes increased afferent vagal stimulation resulting in hyperventilation. CPAP also fights the interstitial edema.
Due to the fact that many of these patients snore, CPAP can also act by decreasing the airway resistance. In snorers, there is a higher decrease in the pleural pressure and therefore, a higher LV pre-load, which is corrected by making the airways more pervious with CPAP.
Several studies have shown the effects of CPAP on CSR of patients with cardiopathies, by reducing the central apnea/hypopnea index (AHI)2,5, 8-12, improving nocturnal oxyhemoglobin saturation (SatO2)2,8-10,12, decreasing the time of CSR during sleep9 and the number of brief awakenings9-12, increasing the percentage of slow-wave sleep9,12. Its effects are also maintained during the day as observed in the LV EF improvement2,11,12, in the NYHA classification of CHF2,9,11,12, in the reduction of diurnal somnolence at the Epworth scale and decreased heart frequency during the state of wakefulness11. It also decreases the sympathetic activity by reducing the concentrations of nocturnal urinary norepinephrine and morning plasma norepinephrine2 and decreases the frequency of ventricular arrhythmias10. It increases the heart transplant free-survival and decreases the mortality/heart transplant rate as shown in a study with more than 2 years of follow-up13. As for quality of life, there was improvement in the "Chronic Heart Failure Questionnaire" score regarding the items dyspnea, fatigue, emotional well-bring, and disease domain11.
Not all patients respond to CPAP. Javaheri10 found a frequency of only 43% of responders (patients whose AHI decreased to less than 15 per hour). The non-responders had a mean AHI of 62 and the responders, a mean AHI of 36, which shows that more severe patients may not respond to CPAP, probably due to the fact that the latter can lead to a tendency to wake up, promoting respiratory instability due to the more elevated pressures used in these patients. Other studies have found a higher frequency of responders, but they had less severe cohorts9.
Contrarily, other authors have shown that CPAP failed to improve CSR14,15, or even showed that it can be deleterious for these patients15. A methodological error that might have contributed to the lack of success of CPAP was the protocol used in pressure adjustment, initiated arbitrarily at 7.5 cmH2O or higher.
Javaheri10 and Naughton et al11 created different ways to titrate the correct pressure, but both are in agreement about starting the titration with a pressure of 5 cmH2O and increasing the pressure gradually until a value that is tolerable by the patient is reached, trying to achieve between 10 to 12 cmH2O. Another possible explanation for the absence of beneficial effects is the CPAP evaluation after just one night of its use14. It has been demonstrated that the benefits of CPAP are achieved with time (there is an increase in EF within 1 to 3 months of use) and the pressure level can also be optimized during treatment.
Recently, an important multicentric study16 that involved 258 patients evaluated long-term use (24 months) of CPAP in cardiopaths. The result, however, was not the expected one. Although it reduced the central apnea index, increased the oxyhemoglobin saturation, improved heart function and reduced the levels of plasma norepinephrine, CPAP failed in demonstrating benefits regarding mortality and transplant-free survival.
In the beginning of the study, the transplant-free survival curve favored the control group, but 18 months later it started to favor the CPAP group, with no statistical difference at the end of the study. These results that did not corroborate the expectations generated by previous studies can be a consequence of more frequent beta-blocker use in comparison to the older ones. The concomitance of CPAP use and beta-blocker has limited the potential to improve the ventricular function obtained with CPAP alone.
An undesirable adverse effect of CPAP is the cardiac output decrease and consequent arterial hypotension, which can be prevented with pressure titration from 5 cmH2O and its gradual elevation for days or weeks as tolerated by the patient. Another common complaint is the discomfort caused by the nasal mask.
Another method of ventilation with positive pressure (Bi-level Positive Airway Pressure, BiPAP) was compared to CPAP, but did not show any advantage when compared to the latter, in addition to its very high cost9.
The main effects of O2 on CSR are: increase of body oxygen stores, preventing the instability of arterial gases and the removal of the hypoxic stimulus to hyperpnea allowing the increase of PaCO2, augmenting the difference between the patient’s PaCO2 and the PaCO2 of the apnea threshold17.
Studies have shown the several benefits of O2 in CSR: AHI reduction18-22, improvement of the nocturnal SatO28,18-22, decrease in the mean time of CSR18,21 and brief awakenings18,20,22, increase of slow wave sleep18,22, reduction in cardiac frequency during the night20. It did not modify symptoms20,21, but improved a cognitive function parameter: the velocity of information processing20. It reduced the sympathetic activation demonstrated by the decrease of nocturnal urinary excretion of noradrenaline21. There was an increase in peak O2 consumption at the ergometric cycle test20, which is a strong predictor of mortality; this leads to speculations about the improvement of survival com O2. Krachman et al8 compared O2 with CPAP in prospective randomized study with 25 patients and concluded that the two modalities of treatment are equally effective, although in this study CPAP as well as O2 were used for only one night. As seen before, CPAP effect depends on its long-term use.
The O2 flow used in these studies varied from 2 to 4 l/min and the response rate to O2 (percentage of those who had the AHI reduced to < 15 per hour) was 39%19. As with CPAP, the responders were those with milder CSR (lower AHI, milder oxyhemoglobin desaturation and higher PaCO2).
The mechanism through which Theophylline acts is uncertain. It is known that it inhibits phosphodiesterase, but at the concentrations used for the treatment of CSR, it does not have the inhibitory effect. At therapeutic concentrations, it competes with adenosine in some of its receptors. At the central nervous system (CNS), adenosine is a respiratory depressor and Theophylline has a respiratory stimulation effect as it competes with the first, preventing central apneas.
It has been demonstrated that Theophylline reduced AHI23,24, improved nocturnal SatO223,24 and decreased total brief awakenings24 and those associated with respiratory alterations23. It did not alter sleep efficiency, sleep stages23,24, or LV EF23. Additionally, it did not alter ventricular arrhythmias, suggesting that it is a safe option for these patients. It is important to know that Javaheri et al23 used O2 in patients due to oxyhemoglobin desaturation during examinations and this fact might have contributed to alterations in the results.
The Theophylline doses used were: 200-300 mg/day (4.3 mg/kg)24 and 3.3 mg/kg, twice a day23. Its defenders justify its use by mentioning the limitations of other therapeutic modalities: low adherence to CPAP and the possibility of inadvertently dislodging the O2 cannula during sleep.
1) CHF drug therapy optimization: In fact, this should be the first-choice treatment, as it is the simplest. Walsh et al22 demonstrated that patients with stable CHF with the use of furosemide alone, showed increase of slow wave sleep and REM sleep, reduction of HAI and desaturation events, as well as CO2 increment at the end of the expiration and ventilation reduction a minute after the addition of captopril 75 mg/day for a month. Dark et al25 studied patients who were admitted due to heart failure decompensation, showing respiratory pattern abnormalities (predominantly central apnea with CSR) in all of them. After CHF compensation during hospital stay with diuretics, vasodilators, antihypertensive drugs, antiarrhythmic drugs and positive inotropics, a new polysomnography was performed with decrease in AHI and a tendency of SatO2improvement.
2) Pacemaker: Left or biventricular pacemaker implant with atrial trigger mode26 showed a reduction in AHI and improvement in SatO2 as well as in the subjective quality of sleep, possibly due to cardiac function improvement. In this study, no patient had a conventional indication of pacemaker.
3) Benzodiazepine drugs: The reason for not using benzodiazepine drugs is the effect of increasing the awakening threshold, as it is a consequence of CSR and can be a perpetuating factor of the problem, due to hyperventilation and hypocapnia, caused by awakening. Studies have shown reduction of the brief awakenings, but no significant decrease in AHI or nocturnal SatO227,28. Special attention should be given to the patients with obstructive apneas, as the benzodiazepine drugs can aggravate them.
4) CO2: The use of CO2 (0.2-1 l/min) mixed with O2 (2l/min) during sleep has been studied, and showed decrease in the duration of CSR and improvement in SatO2, but decreased the quality of sleep and increased the sympathetic activity29. Additionally, the resulting hypercapnia increases the left and right ventricular post-load. Therefore, it must not be indicated for patients with CHF.
5) Adaptive servo-ventilation (ASV): This new ventilatory modality consists of a variable ventilatory support that adapts depending on the phase of the respiration, being higher in apnea and lower in hyperventilation periods. It corrected CSR, objectively reducing the diurnal somnolence, plasma BNP levels (a marker of heart failure severity) and the excretion of urinary metadrenaline30. It improved the quality of sleep (by increasing total sleep time, sleep efficiency, percentage of REM and slow wave sleep and decreasing the brief awakening index) and reduced AHI and desaturations, when compared to controls. There were significant differences in some of these parameters in comparison to CPAP31.
Although it is the most studied treatment modality, the use of CPAP in CSR is still controversial and the experience of this treatment in Brazil is still scarce, as CPAP is not provided by the public Health Services and most patients have difficulty to buy it. O2 is an option for patients who are intolerant to CPAP or who cannot use it for any other reason. However, the long-term survival of this treatment modality has yet to be assessed. The other types of treatment reported here need further studies. CSR is a frequent event in cardiopaths and it is associated with a worse prognosis; thus, the correct diagnosis and treatment are of utmost importance.
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Ivan Guerra de Araújo Freitas Rua Dr. Diogo de Faria, 1226/84 04037-004 – São Paulo, SP - Brazil E-mail:
Manuscript received January 11, 2006; revised manuscript received August 15, 2006; accepted October 9, 2006.
10. Javaheri S. Effects of continuous positive airway pressure on sleep apnea and ventricular irritability in patients with heart failure. Circulation. 2000; 101: 392-7.