Andrea H. S. Loewen

Declining Kidney Function Increases the Prevalence of Sleep Apnea and Nocturnal Hypoxia

BACKGROUND Sleep apnea is an important comorbidity in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Although the increased prevalence of sleep apnea in patients with ESRD is well established, few studies have investigated the prevalence of sleep apnea in patients with nondialysis-dependent kidney disease, and no single study, to our knowledge, has examined the full spectrum of kidney function. We sought to determine the prevalence of sleep apnea and associated nocturnal hypoxia in patients with CKD and ESRD. We hypothesized that the prevalence of sleep apnea would increase progressively as kidney function declines. METHODS Two hundred fifty-four patients were recruited from outpatient nephrology clinics and hemodialysis units. All patients completed an overnight cardiopulmonary monitoring test to determine the prevalence of sleep apnea (respiratory disturbance index ≥ 15) and nocturnal hypoxia (oxygen saturation < 90% for ≥ 12% of monitoring). Patients were stratified into three groups based on estimated glomerular filtration rate (eGFR) as follows: eGFR ≥ 60 mL/min/1.73 m(2) (n = 55), CKD (eGFR < 60 mL/min/1.73 m(2) not on dialysis, n = 124), and ESRD (on hemodialysis, n = 75). RESULTS The prevalence of sleep apnea increased as eGFR declined (eGFR ≥ 60 mL/min/1.73 m(2), 27%; CKD, 41%; ESRD, 57%; P = .002). The prevalence of nocturnal hypoxia was higher in patients with CKD and ESRD (eGFR ≥ 60 mL/min/1.73 m(2), 16%; CKD, 47%; ESRD, 48%; P < .001). CONCLUSIONS Sleep apnea is common in patients with CKD and increases as kidney function declines. Almost 50% of patients with CKD and ESRD experience nocturnal hypoxia, which may contribute to loss of kidney function and increased cardiovascular risk.

Genioglossus activity available via non-arousal mechanisms vs. that required for opening the airway in obstructive apnea patients

It is generally believed that reflex recruitment of pharyngeal dilator muscles is insufficient to open the airway of obstructive apnea (OSA) patients once it is closed and, therefore, that arousal is required. Yet arousal promotes recurrence of obstruction. There is no information about how much dilator [genioglossus (GG)] activation is required to open the airway (GG Opening Threshold) or about the capacity of reflex mechanisms to increase dilator activity before/without arousal (Non-Arousal Activation). The relationship between these two variables is important for ventilatory stability. We measured both variables in 32 OSA patients (apnea-hypopnea index 74 ± 42 events/h). GG activity was monitored while patients were on optimal continuous positive airway pressure (CPAP). Zopiclone was administered to delay arousal. Maximum GG activity (GG(MAX)) and airway closing pressure (P(CRIT)) were measured. During stable sleep CPAP was decreased to 1 cmH(2)O to induce obstructive events and the dial-downs were maintained until the airway opened with or without arousal. GG activity at the instant of opening (GG Opening Threshold) was measured. GG Opening Threshold averaged only 10.4 ± 9.5% GG(Max) and did not correlate with P(CRIT) (r = 0.04). Twenty-six patients had >3 openings without arousal, indicating that Non-Arousal Activation can exceed GG Opening Threshold in the majority of patients. GG activity reached before arousal in Arousal-Associated Openings was only 5.4 ± 4.6% GG(MAX) below GG Opening Threshold. We conclude that in most patients GG activity required to open the airway is modest and can be reached by non-arousal mechanisms. Arousals occur in most cases just before non-arousal mechanisms manage to increase activity above GG Opening Threshold. Measures to reduce GG Opening Threshold even slightly may help stabilize breathing in many patients.

Response of genioglossus muscle to increasing chemical drive in sleeping obstructive apnea patients.

STUDY OBJECTIVES Subjects with a collapsible upper airway must activate their pharyngeal dilators sufficiently in response to increasing chemical drive if they are to maintain airway patency without arousal from sleep. Little is known about the response of pharyngeal dilators to increasing chemical drive in these subjects. We wished to determine, in obstructive apnea patients, the response of the genioglossus to increasing chemical drive and the contribution of mechanoreceptor feedback to this response. DESIGN Physiological study. SETTING University-based sleep laboratory. PATIENTS 20 patients with obstructive apnea. INTERVENTIONS Genioglossus activity was monitored during overnight polysomnography on optimal continuous positive airway pressure (CPAP). Intermittently, inspired gases were altered to produce different levels of ventilatory stimulation. CPAP was then briefly reduced to 1.0 cm H(2)O (dial-down), inducing an obstruction. MEASUREMENTS AND RESULTS Without mechanoreceptor feedback (i.e., on CPAP) the increase in genioglossus activity as ventilation increased from 6.1 ± 1.4 to 16.1 ± 4.8 L/min was modest (ΔTonic activity 0.3% ± 0.5%maximum; ΔPhasic activity 1.7% ± 3.4%maximum). Genioglossus activity increased immediately upon dial-down, reflecting mechanoreceptor feedback, but only when ventilation before dial-down exceeded a threshold value. This threshold varied among patients and, once surpassed, genioglossus activity increased briskly with further increases in chemical drive (1.1% ± 0.84%GG(MAX) per L/min increase in V(E)). CONCLUSIONS In sleeping obstructive apnea patients: (1) Mechanoreceptor feedback is responsible for most of the genioglossus response to chemical drive. (2) Mechanoreceptor feedback is effective only above a threshold chemical drive, which varies greatly among patients. These findings account in part for the highly variable relation between pharyngeal mechanical abnormalities and apnea severity.

Clinical presentation of obstructive sleep apnea in patients with chronic kidney disease.

BACKGROUND Obstructive sleep apnea (OSA) is an important and common comorbidity in patients with chronic kidney disease (CKD). However, few studies have addressed how OSA presents in this patient population and whether it is clinically apparent. OBJECTIVE The objectives of this study were to determine if the prevalence and severity of sleep related symptoms distinguished CKD patients with OSA from those without apnea, and whether the clinical presentation of OSA in CKD patients differed from the general OSA population. METHODS One hundred nineteen patients were recruited from outpatient nephrology clinics. All patients completed a sleep history questionnaire, the Epworth Sleepiness Scale (daytime sleepiness, ESS > 10), the Pittsburgh Sleep Quality Index (poor sleep quality, PSQI > 5), and underwent overnight cardiopulmonary monitoring for determination of sleep apnea (respiratory disturbance index ≥ 15). CKD patients with OSA (n = 46) were compared to (1) CKD patients without OSA (n = 73) and (2) OSA patients without CKD (n = 230) who were referred to the sleep centre. RESULTS The prevalence of OSA symptoms and PSQI scores did not differ between CKD patients with OSA and CKD patients without apnea. Although the prevalence of daytime sleepiness was higher in CKD patients with OSA compared to CKD patients without apnea (39% vs. 19%, p = 0.033), both daytime sleepiness and other symptoms of sleep apnea were considerably less frequent than in OSA patients without a history of kidney disease. CONCLUSIONS The presence of OSA in patients with CKD is unlikely to be clinically apparent. Consequently, objective cardiopulmonary monitoring during sleep is required to reliably identify this comorbidity.

Improving rates of pneumococcal vaccination on discharge from a tertiary center medical teaching unit: A prospective intervention

BackgroundPneumococcal disease causes significant morbidity and mortality in at-risk individuals, and is complicated by emerging antibiotic resistance. An effective, safe and cost-effective vaccine is available, but despite this many patients who would benefit from pneumococcal vaccination remain unvaccinated. The purpose of this study was to determine the rates of missed opportunities to provide pneumococcal vaccination to patients being discharged from a tertiary center medical teaching unit and to determine if a nurse coordinator-based intervention would increase rates of pneumococcal vaccination prior to discharge home.MethodsWe conducted a prospective, controlled study in the setting of a Medical Teaching Unit at a tertiary care centre to assess the impact of a nurse coordinator based intervention on the rates of vaccination of eligible patients on discharge home. The rates of vaccination during an eight-week usual-care period (February 20 to April 16, 2002) and an eight-week intervention period (April 22 to June 16, 2002) were compared.ResultsPrior to the intervention none of thirty-eight eligible patients were vaccinated prior to discharge home from the Medical Teaching Unit. After the intervention 27 (54%) of fifty eligible patients were vaccinated prior to discharge.ConclusionThere are significant missed opportunities to provide pneumococcal vaccination to inpatients who are discharged home from a medical unit. Using a patient care coordinator we were able to significantly improve the rates of vaccination on discharge.

Diagnostic value of screening instruments for identifying obstructive sleep apnea in kidney failure.

BACKGROUND Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have a high prevalence of obstructive sleep apnea (OSA) that can have significant clinical implications. An accurate clinical screening tool for OSA that identifies patients for further diagnostic testing would assist in the identification of this comorbidity. The Berlin Questionnaire (BQ), Adjusted Neck Circumference (ANC), and STOP-BANG questionnaire are 3 such instruments that have been validated in patients with normal kidney function. OBJECTIVE The objective of this study was to determine the validity of these screening instruments in patients with CKD and ESRD, using overnight cardiopulmonary monitoring to diagnose OSA. METHODS One hundred seventy-two patients were recruited from nephrology clinics and hemodialysis units (CKD: n = 109; ESRD: n = 63). All patients completed the BQ, ANC, STOP-BANG, and overnight cardiopulmonary monitoring to diagnose OSA (respiratory disturbance index [RDI] ≥ 15). Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for the BQ, ANC, and STOP-BANG. RESULTS Obstructive sleep apnea was present in 41 CKD patients (38%) and 32 ESRD patients (51%). All screening instruments had satisfactory sensitivity (56% to 94%) but poor specificity (29% to 77%) and low accuracy (51% to 69%) in both CKD and ESRD patients with RDI ≥ 15. Using an RDI ≥ 30 yielded similar results. CONCLUSIONS Current screening questionnaires do not accurately identify patients at high risk for OSA or rule out the presence of OSA in patients with CKD and ESRD. Consequently, objective monitoring during sleep is required to reliably identify sleep apnea in these patient populations.

The prevalence of restless legs syndrome across the full spectrum of kidney disease.

STUDY OBJECTIVES Although restless legs syndrome (RLS) is common and well recognized as an important and potentially treatable cause of sleep disruption in end-stage renal disease (ESRD), few studies have evaluated the prevalence of RLS and its impact on sleep in the non-dialysis-dependent chronic kidney disease (CKD) population. The objectives of the study were to determine the prevalence of RLS across the full spectrum of kidney disease and to assess the impact of RLS on sleep quality and daytime function. METHODS Five hundred patients were recruited from nephrology clinics and were stratified according to estimated glomerular filtration rate (EGFR): eGFR ≥ 60 mL/min/1.73m(2) (n = 127), CKD (eGFR < 60, not on dialysis, n = 242), and ESRD (on hemodialysis, n = 131). All subjects completed a sleep and medical history questionnaire, an RLS questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). RESULTS The prevalence of RLS did not differ among the three groups (18.9% [eGFR ≥ 60], 26% (CKD), and 26% (ESRD) p = 0.27). However, many symptoms of sleep disruption were more common in patients with RLS, and RLS was independently correlated with the PSQI score both in the full cohort (OR = 2.63, CI = 1.60-4.00, p < 0.001) and the CKD group (OR = 2.39, CI = 1.20-4.79, p = 0.014). CONCLUSIONS RLS is common in non-dialysis-dependent CKD patients and is an important source of sleep disruption.

Validity of ICD-9-CM administrative data for determining eligibility for pneumococcal vaccination triggers.

The purpose of this study was to evaluate the efficacy of medical record administrative data as coded by the International Classification of Diseases, Ninth Revision, for triggering pneumococcal vaccination reminders of patients following discharge from a tertiary care adult teaching hospital. A retrospective computerized search was conducted using administrative discharge data to detect patients admitted to the medical teaching unit who met clinical criteria for pneumococcal vaccination according to Canadian immunization guidelines. For identification of persons eligible for vaccination, administrative discharge data showed a sensitivity of 83% (confidence interval [CI], 0.73-0.92) and a specificity of 78% (CI, 0.64-0.91), with a positive predictive value of 87% (CI, 0.83-0.90) and a negative predictive value of 72% (CI, 0.58-0.86). The reasonably high specificity and sensitivity of diagnostic codes in administrative data could be used to trigger appropriate pneumococcal vaccination among eligible patients after hospital discharge.

Using intelligent agents to repurpose administrative data in fostering disease prevention in an outpatient context: the case of pneumococcal vaccination

The use of intelligent agents is proposed as an economical way to repurpose administrative data in order to foster a program of disease prevention in an outpatient context. A retrospective computerized search was conducted using administrative hospital discharge data to identify patients admitted to a medical teaching unit who met the Canadian Immunization criteria for pneumococcal vaccination over a one-year period. For identification of persons eligible for pneumococcal vaccination, administrative discharge data was shown to have a sensitivity of 83%, (confidence interval [CI] 0.73-0.92) and a specificity of 78% CI (0.64-0.91), with a positive predictive value [PPV] of 87%, CI (0.83- 0.90) and a negative predictive value [NPV] of 72%, CI (0.58-0.86). This study demonstrates that administrative data appear promising as the basis for certain clinical applications. Specifically, the reasonably high specificity and sensitivity of diagnostic codes in administrative data could be utilized to trigger appropriate pneumococcal vaccination after hospital discharge among eligible patients who might otherwise never receive this efficacious intervention. Reminder systems in a hospital setting have received mixed results although positive results have been shown in several outpatient settings but using clinical data. Therefore, before a reminder system using administrative data in an outpatient context is implemented it seemed prudent to investigate this issue further.

Limitations of split-night polysomnography for the diagnosis of nocturnal hypoventilation and titration of non-invasive positive pressure ventilation in amyotrophic lateral sclerosis.

Abstract Split-night polysomnography is performed at our centre in all patients with ALS who require assessment for nocturnal hypoventilation and their response to non-invasive ventilation. The purpose of this study was to determine how successful this practice has been, reflected by whether a complete assessment was achieved by a single split-night polysomnogram. We undertook a systematic, retrospective review of all consecutive split-night polysomnograms in ALS patients between 2005 and 2012. A total of 47 cases were reviewed. Forty-three percent of patients had an incomplete test, resulting in a recommendation to repeat the polysomnogram. Poor sleep efficiency and absence of REM sleep in the diagnostic portion of the study were strongly associated with incomplete studies. Clinical variables that reflect severity of ALS (FVC, PaCO2, ALSFRS-R) and use of REM-suppressing antidepressants or sedative-hypnotics were not associated with incomplete split-night polysomnogram. In conclusion, a single, split-night polysomnogram is frequently inconclusive for the assessment of nocturnal hypoventilation and complete titration of non-invasive positive pressure ventilation in patients with ALS. Poor sleep efficiency and absence of REM sleep are the main limitations of split-night polysomnography in this patient population.