Darren Mansfield

Raised Sympathetic Nerve Activity in Heart Failure and Central Sleep Apnea Is Due to Heart Failure Severity

Background—Congestive heart failure (CHF) patients with central sleep apnea (CHF-CSA) have elevated plasma norepinephrine (NE) compared with CHF patients without apnea (CHF-N). Patients with CHF-CSA also demonstrate higher mean pulmonary artery pressure (PAP), which is suggestive of worse cardiac function. Whether CSA contributes to chronic elevation of sympathetic nerve activity or is associated with more severe CHF remains unknown. We measured awake total body and cardiac NE spillover and related these to measurements of cardiac hemodynamics and apnea severity in CHF patients with CSA, with normal breathing, and with obstructive sleep apnea (CHF-OSA). Methods and Results—A total of 55 CHF patients underwent right heart catheterization and measurements of total body and cardiac NE spillover using NE radioisotope dilution methodology. After polysomnography, patients were grouped by apnea type: 19 were CHF-N, 15 were CHF-OSA, and 21 were CHF-CSA. Compared with the CHF-N and CHF-OSA groups, the CHF-CSA group had significantly higher total body NE spillover (4.62±0.56 versus 4.47±0.54 versus 6.95±0.89 nmol/min, respectively;P =0.03), cardiac NE spillover (0.25±0.05 versus 0.21±0.05 versus 0.42±0.06 nmol/min, respectively;P =0.02) and mean PAP (23.5±2.4 versus 21.2±0.8 versus 30.4±0.2 mm Hg, respectively;P <0.02). However, controlling for severity of CHF resulted in no significant differences in NE kinetics among the 3 groups. In a stepwise regression, only mean PAP independently correlated with total body (r =0.33, P =0.03) and cardiac NE spillover (r =0.44, P =0.002). Sleep apnea severity bore no relationship to markers of sympathetic nerve activity. Conclusion—Total body and cardiac sympathetic nerve activity are elevated in CHF-CSA compared with CHF-OSA and CHF-N patients and are related to heart failure not apnea severity.

Acute Effects of Continuous Positive Airway Pressure on Cardiac Sympathetic Tone in Congestive Heart Failure

Background—Depressed ventricular performance and neurohormonal activation are key pathophysiological features of congestive heart failure (CHF). Although angiotensin-converting enzyme inhibitors and &bgr;-adrenoceptor blockers exert beneficial effects in CHF, mortality remains unacceptably high, and the development of further therapeutic approaches is warranted. Recent data suggest that continuous positive airway pressure (CPAP) may be of benefit in the treatment of CHF, although the mechanism for this action is incompletely understood. Methods and Results—In the present study, we examined the effect of short-term CPAP (10 cm H2O for 10 minutes) on hemodynamics (Swan Ganz catheter) and total systemic and cardiac sympathetic activity (norepinephrine spillover method) in 14 CHF patients in New York Heart Association class III. The application of CPAP was associated with a fall in cardiac output (4.8±0.3 to 4.4±0.2 L/min;P <0.05) and a significant reduction in cardiac norepinephrine spillover (370±58 to 299±55 pmol/min;P <0.05), although total systemic norepinephrine spillover was unchanged. Conclusion—The short-term application of CPAP results in an inhibition of cardiac sympathetic nervous activity. Further investigation into the potential value of long-term CPAP in CHF patients is warranted.

A comparison of conventional dialytic therapy and acute continuous hemodiafiltration in the management of acute renal failure in the critically ill

OBJECTIVE To compare and contrast the clinical outcomes in critically ill patients with acute renal failure managed with either acute continuous hemodiafiltration or conventional dialytic therapies. DESIGN Retrospective review of the medical records of 167 consecutive cases of acute renal failure treated at a single center (July 1982-July 1991). Scoring for illness severity (APACHE II, number of failing organs) and assessment of outcome in terms of biochemical control of azotemia, ARF therapy-related morbidity, and overall morbidity and mortality. SETTING Tertiary institution. PATIENTS 167 consecutive critically ill patients with multiorgan failure and acute renal failure. MEASUREMENTS AND MAIN RESULTS 84 patients received conventional dialytic therapy (CDT) (1982-1988) and 83 acute continuous hemodiafiltration (ACHD) (1988-1991). The etiology of ARF and illness severity indices were similar in both groups (organ failure scores: CDT 3.9 vs. ACHD 4.1; NS). All patients were critically ill, with more severely ill patients within the ACHD groups (mean APACHE II score: CDT 25.8 vs. ACHD 28.1; p < .01). There were no significant differences in pretreatment serum creatinine, glucose, bicarbonate and phosphate, white cell and platelet counts, incidence of disseminated intravascular coagulation, prevalence of sepsis, or evidence of pulmonary and/or peripheral edema. Overall survival was 29.8% for the CDT groups and 41% for the ACHD group (NS). When patients were stratified by severity of illness, survival in those with 2 to 4 failing organs was significantly greater in the ACHD group (CDT 31.1% vs. ACHD 53.8%; p < .025). Similarly, overall survival in patients with intermediate APACHE II scores (24 to 29) was significantly better in those treated with ACHD (CDT 12.5% vs. ACHD 46.4%; p < .025). During the course of ARF, in comparison to CDT, ACHD was associated with greater overall reductions in serum creatinine, and in phosphate and plasma urea, and an increased net nutritional intake. CONCLUSIONS ACHD provided biochemical and outcome indicator advantages over conventional dialytic therapy. In patients with 2 to 4 failing organs or an intermediate APACHE II score (24 to 29) a significant survival advantage was demonstrated for ACHD over CDT. Although this study is a retrospective analysis, with all the inherent limitations of such studies, it suggests that ACHD is the treatment of choice for ARF in the critically ill, with maximum benefits seen in those with 2 to 4 failing organs and/or intermediate APACHE II scores.

Acute renal failure in critical illness. Conventional dialysis versus acute continuous hemodiafiltration.

The dialytic therapy of choice in critically ill patients with acute renal failure (ARF) is a matter of controversy. The clinical outcome of such patients managed with either conventional dialytic therapy (CDT) or acute continuous hemodiafiltration (ACHD) was compared through retrospective review of medical records from the intensive care unit of a tertiary institution. Records from 167 critically ill patients with ARF consecutively treated in the same intensive care unit were reviewed. Eighty-four patients with ARF treated by CDT were compared to 83 treated with ACHD. The etiology of ARF and the degree of illness severity were similar in both groups (failing organs: CDT 3.9 vs. ACHD 4.1; mean APACHE II score: CDT 25.8 vs. ACHD 28.1). Overall survival was 29.8% for the CDT patients and 41% for the ACHD group (NS). In those with two to four failing organs, survival was greater in the ACHD group (53.8% vs. 31.1%; p < 0.025). This was also true for patients with an intermediate APACHE II score (24-29) who demonstrated better survival when treated by ACHD (46.4% vs. 12.5%; p < 0.025). Acute continuous hemodiafiltration was associated with better control of azotemia and hyperphosphatemia and increased nutritional intake. This retrospective study suggests that ACHD may offer clinically significant advantages over CDT, particularly in patients with an intermediate degree of critical illness severity.

Effects of continuous positive airway pressure on lung function in patients with chronic obstructive pulmonary disease and sleep disordered breathing

Sleep disordered breathing (SDB), namely hypoventilation and obstructive sleep apnoea, occur in about 50% of patients with severe chronic obstructive pulmonary disease (COPD). Previous studies that have investigated the reversal of SDB in such patients with nasally applied intermittent positive airway pressure have reported a fall in PaCO2 but little change in airflow obstruction. We reasoned that the lack of improvement in airflow obstruction may be due to insufficient expiratory pressure. Accordingly, we sought to determine the effects of chronic nasal continuous positive airway pressure (CPAP), at highest tolerable levels, upon blood gases and airflow obstruction in patients with severe COPD and SDB.

Continuous positive airway pressure decreases myocardial oxygen consumption in heart failure

The aim of the present study was to investigate the effects of CPAP (continuous positive airway pressure) support on myocardial energetics in patients with CHF (congestive heart failure). CPAP has been shown to decrease left ventricular afterload and to produce favourable short- and long-term haemodynamic and neurohormonal benefits in CHF patients. The mechanisms responsible for these actions are not completely understood. We measured the haemodynamic and myocardial metabolic response to the acute (10 min) application of CPAP in CHF patients. Myocardial VO(2) (O(2) consumption) and VCO(2) (CO(2) production) were measured by simultaneous arterial and coronary sinus blood sampling. The application of CPAP resulted in a significant decrease in left ventricular stroke work (97+/-12 to 83+/-9 g.m; P <0.05) and myocardial VO(2) (0.32+/-0.03 to 0.25+/-0.01 ml of O(2)/beat; P <0.05). Myocardial mechanical efficiency, however, was unchanged. CPAP application decreases myocardial work and VO(2). This effect on myocardial energetics could account for some of the favourable effects of CPAP in CHF patients.

Circadian Melatonin Rhythm Following Traumatic Brain Injury.

Background: Sleep-wake disturbances are highly prevalent following traumatic brain injury (TBI), impeding rehabilitaion and quality of life. However, the mechanisms underlying these sleep disturnbances are unclear, and efficacious treatments are lacking. To investigate possible mechanisms underlying sleep disturbance in TBI, we examined characteristics of the circadian rhythm of melatonin, a hormone involved in sleep-wake regulation. We compared TBI patients reporting sleep disturbance with age- and gender-matched healthy volunteers. Methods: We conducted an overnight observational study with salivary melatonin samples collected hourly in 9 patients with severe TBI and 9 controls. Salivary dim light melatonin onset (DLMO) as well as melatonin synthesis onset (SynOn) and offset (SynOff) were used to determine circadian timing. Total overnight salivary melatonin production was calculated as the area under the curve from melatonin synthesis onset to offset. Results: Compared with healthy individuals, TBI patients showed 42% less melatonin production overnight (d = 0.87; P = .034). The timing of DLMO was delayed by approximately 1.5 hours in patients with TBI compared with controls (d = 1.23; P = .003). Conclusions: In patients with TBI, melatonin production was attenuated overnight, and the timing of melatonin secretion was delayed. We suggest that disruption to the circadian regulation of melatonin synthesis is a feature of severe TBI, possibly contributing to the sleep difficulties that are commonly reported in this population.

Sleep Disturbances in Traumatic Brain Injury: A Meta-Analysis.

STUDY OBJECTIVES Sleep disturbances are frequently reported following traumatic brain injury (TBI); however, the exact disturbances remain unclear. This meta-analysis aimed to characterize sleep disturbance in community dwelling patients with TBI as compared to controls. METHODS Two investigators independently conducted a systematic search of multiple electronic databases from inception to May 27, 2015. Studies were selected if they compared sleep in community dwelling individuals with TBI relative to a control population without head injury. Data were pooled in meta-analysis with outcomes expressed as the standard mean difference (SMD) and 95% confidence interval (CI). The primary outcomes were derived from polysomnography and secondary outcomes were derived from subjective sleep measures. RESULTS Sixteen studies were included, combining 637 TBI patients and 567 controls, all of whom were community dwelling. Pooled polysomnography data revealed that TBI patients had poorer sleep efficiency (SMD = -0.47, CI: -0.89, -0.06), shorter total sleep duration (SMD = -0.37, CI: -0.59, -0.16), and greater wake after sleep onset time (SMD = 0.60, CI: 0.33, 0.87). Although sleep architecture was similar between the groups, a trend suggested that TBI patients may spend less time in REM sleep (SMD = -0.22, CI: -0.45, 0.01). Consistent with polysomnographic derangement, TBI patients reported greater subjective sleepiness and poorer perceived sleep quality. CONCLUSIONS The evidence suggests that TBI is associated with widespread objective and subjective sleep deficits. The present results highlight the need for physicians to monitor and address sleep deficits following TBI.

How to assess, diagnose, refer and treat adult obstructive sleep apnoea: a commentary on the choices.

Obstructive sleep apnoea (OSA) determined by polysomnography is highly prevalent, affecting about 25% of men and 10% of women in the United States, although most have few or no symptoms. Symptomatic moderate to severe OSA has major health implications related to daytime sleepiness, such as increased accidents, altered mood and loss of productivity in the workplace. Severe OSA may increase the risk of cardiovascular disease independent of daytime sleepiness. A major challenge is to correctly identify, from the large community pool of disease, people with symptoms and those at risk of long‐term complications. For treatment plans to achieve quality patient outcomes, clinicians must have a clear understanding of patients’ symptoms and their motivations for presentation, and be knowledgeable about the evidence surrounding the health risks of OSA and the relative merits of the various diagnostic and treatment options available. The diagnosis of OSA represents a teachable moment to target adverse lifestyle factors such as excessive weight, excessive alcohol consumption and smoking, which may be contributing to OSA and long‐term cardiometabolic risk. OSA assessment and management has traditionally involved specialist referral and in‐laboratory polysomnography. However, these services may not always be easy to access. Controlled studies have shown that patients with a high pretest probability of symptomatic, moderate to severe OSA can be managed well in primary care, or by skilled nurses with appropriate medical backup, using simplified ambulatory models of care. The future of sleep apnoea assessment and management will likely include models of care that involve early referral to specialists of patients with complex or atypical presentations, and an upskilled and supported primary care workforce to manage symptomatic, uncomplicated, high pretest probability disease.

Cognitive Behavior Therapy to Treat Sleep Disturbance and Fatigue After Traumatic Brain Injury: A Pilot Randomized Controlled Trial

OBJECTIVE To evaluate the efficacy of adapted cognitive behavioral therapy (CBT) for sleep disturbance and fatigue in individuals with traumatic brain injury (TBI). DESIGN Parallel 2-group randomized controlled trial. SETTING Outpatient therapy. PARTICIPANTS Adults (N=24) with history of TBI and clinically significant sleep and/or fatigue complaints were randomly allocated to an 8-session adapted CBT intervention or a treatment as usual (TAU) condition. INTERVENTIONS Cognitive behavior therapy. MAIN OUTCOME MEASURES The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) posttreatment and at 2-month follow-up. Secondary measures included the Insomnia Severity Index, Fatigue Severity Scale, Brief Fatigue Inventory (BFI), Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. RESULTS At follow-up, CBT recipients reported better sleep quality than those receiving TAU (PSQI mean difference, 4.85; 95% confidence interval [CI], 2.56-7.14). Daily fatigue levels were significantly reduced in the CBT group (BFI difference, 1.54; 95% CI, 0.66-2.42). Secondary improvements were significant for depression. Large within-group effect sizes were evident across measures (Hedges g=1.14-1.93), with maintenance of gains 2 months after therapy cessation. CONCLUSIONS Adapted CBT produced greater and sustained improvements in sleep, daily fatigue levels, and depression compared with TAU. These pilot findings suggest that CBT is a promising treatment for sleep disturbance and fatigue after TBI.