Noninvasive ventilation as a weaning strategy for mechanical ventilation in adults with respiratory failure: a Cochrane systematic review.

BACKGROUND: Noninvasive ventilation has been studied as a means of reducing complications among patients being weaned from invasive mechanical ventilation. We sought to summarize evidence comparing noninvasive and invasive weaning and their effects on mortality. METHODS: We identified relevant randomized and quasirandomized trials through searches of databases, conference proceedings and grey literature. We included trials comparing extubation and immediate application of noninvasive ventilation with continued invasive weaning in adults on mechanical ventilation. Two reviewers each independently screened citations, assessed trial quality and abstracted data. Our primary outcome was mortality. RESULTS: We identified 16 trials involving 994 participants, most of whom had chronic obstructive pulmonary disease (COPD). Compared with invasive weaning, noninvasive weaning significantly reduced mortality (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.36 to 0.80), weaning failures (RR 0.63, 95% CI 0.42 to 0.96), ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to 0.43), length of stay in the intensive care unit (mean difference [MD] -5.59 d, 95% CI -7.90 to -3.28) and in hospital (MD -6.04 d, 95% CI -9.22 to -2.87), and total duration of mechanical ventilation (MD -5.64 d, 95% CI -9.50 to -1.77). Noninvasive weaning had no significant effect on the duration of ventilation related to weaning, but significantly reduced rates of tracheostomy (RR 0.19, 95% CI 0.08 to 0.47) and reintubation (RR 0.65, 95% CI 0.44 to 0.97). Mortality benefits were significantly greater in trials enrolling patients with COPD than in trials enrolling mixed patient populations (RR 0.36 [95% CI 0.24 to 0.56] v. RR 0.81 [95% CI 0.47 to 1.40]). INTERPRETATION: Noninvasive weaning reduces rates of death and pneumonia without increasing the risk of weaning failure or reintubation. In subgroup analyses, mortality benefits were significantly greater in patients with COPD.

Noninvasive positive-pressure ventilation as a weaning strategy for intubated adults with respiratory failure.

BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) provides ventilatory support without the need for an invasive airway. Interest has emerged in using NPPV to facilitate earlier removal of an endotracheal tube and to decrease complications associated with prolonged intubation. OBJECTIVES: We evaluated studies in which invasively ventilated adults with respiratory failure of any cause (chronic obstructive pulmonary disease (COPD), non-COPD, postoperative, nonoperative) were weaned by means of early extubation followed by immediate application of NPPV or continued IPPV weaning. The primary objective was to determine whether the noninvasive positive-pressure ventilation (NPPV) strategy reduced all-cause mortality compared with invasive positive-pressure ventilation (IPPV) weaning. Secondary objectives were to ascertain differences between strategies in proportions of weaning failure and ventilator-associated pneumonia (VAP), intensive care unit (ICU) and hospital length of stay (LOS), total duration of mechanical ventilation, duration of mechanical support related to weaning, duration of endotracheal mechanical ventilation (ETMV), frequency of adverse events (related to weaning) and overall quality of life. We planned sensitivity and subgroup analyses to assess (1) the influence on mortality and VAP of excluding quasi-randomized trials, and (2) effects on mortality and weaning failure associated with different causes of respiratory failure (COPD vs. mixed populations). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 5, 2013), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), proceedings from four conferences, trial registration websites and personal files; we contacted authors to identify trials comparing NPPV versus conventional IPPV weaning. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing early extubation with immediate application of NPPV versus IPPV weaning in intubated adults with respiratory failure. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and abstracted data according to prespecified criteria. Sensitivity and subgroup analyses assessed (1) the impact of excluding quasi-randomized trials, and (2) the effects on selected outcomes noted with different causes of respiratory failure. MAIN RESULTS: We identified 16 trials, predominantly of moderate to good quality, involving 994 participants, most with chronic obstructive pulmonary disease (COPD). Compared with IPPV weaning, NPPV weaning significantly decreased mortality. The benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24 to 0.56) versus mixed populations (RR 0.81, 95% CI 0.47 to 1.40). NPPV significantly reduced weaning failure (RR 0.63, 95% CI 0.42 to 0.96) and ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to 0.43); shortened length of stay in an intensive care unit (mean difference (MD) -5.59 days, 95% CI -7.90 to -3.28) and in hospital (MD -6.04 days, 95% CI -9.22 to -2.87); and decreased the total duration of ventilation (MD -5.64 days, 95% CI -9.50 to -1.77) and the duration of endotracheal mechanical ventilation (MD - 7.44 days, 95% CI -10.34 to -4.55) amidst significant heterogeneity. Noninvasive weaning also significantly reduced tracheostomy (RR 0.19, 95% CI 0.08 to 0.47) and reintubation (RR 0.65, 95% CI 0.44 to 0.97) rates. Noninvasive weaning had no effect on the duration of ventilation related to weaning. Exclusion of a single quasi-randomized trial did not alter these results. Subgroup analyses suggest that the benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD versus mixed populations. AUTHORS' CONCLUSIONS: Summary estimates from 16 trials of moderate to good quality that included predominantly participants with COPD suggest that a weaning strategy that includes NPPV may reduce rates of mortality and ventilator-associated pneumonia without increasing the risk of weaning failure or reintubation.

Dopamine alters tactile perception in Parkinson's disease.

BACKGROUND: Abnormal somatosensory processing may contribute to motor impairments observed in Parkinson's disease (PD). Dopaminergic medications have been shown to alter somatosensory processing such that tactile perception is improved. In PD, it remains unclear whether the temporal sequencing of tactile stimuli is altered and if dopaminergic medications alter this perception. METHODS: Somatosensory tactile perception was investigated using temporal order judgment in patients with Parkinson's disease on and off dopaminergic medications and in aged-matched healthy controls. Measures of temporal order judgment were acquired using computer controlled stimulation to digits 2 and 3 on the right hand and subjects were required to determine which stimuli occurred first. Two experimental tasks were compared, temporal order judgment without and with synchronization whereby digits 2 and 3 were vibrated synchronously in advance of the temporal order judgment sequence of stimuli. RESULTS: Temporal order judgment in PD patients of and on medications were similar to controls. Temporal order judgment preceded by synchronous vibration impaired tactical acuity in controls and in PD patients off medications to similar degrees, but this perceptual impairment by synchronous vibration was not present in PD patients on medications. CONCLUSIONS: These findings suggest that dopamine in PD reduces cortico-cortical connectivity with SI and this leads to changes in tactical sensitivity.

Bilateral somatosensory evoked potentials following intermittent theta-burst repetitive transcranial magnetic stimulation.

BACKGROUND: Intermittent theta-burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation that may alter cortical excitability in the primary somatosensory cortex (SI). The present study investigated the effects of iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs) recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS. RESULTS: Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was significantly increased for 5 minutes from non-stimulated SI and for 15 to 25 minutes from stimulated SI. Subcortical potentials recorded bilaterally remained unaltered following iTBS. CONCLUSION: We conclude that iTBS increases the cortical excitability of SI bilaterally and does not alter thalamocortical afferent input to SI. ITBS may provide one avenue to induce cortical plasticity in the somatosensory cortex.

Efficacy of a Guideline-Recommended Risk-Reduction Program to Improve Cardiovascular and Limb Outcomes in Patients With Peripheral Arterial Disease.

IMPORTANCE: Patients with peripheral arterial disease (PAD) are at a high risk for cardiovascular events, yet, to our knowledge, no studies have examined the effect of a comprehensive risk-reduction program on long-term outcomes for patients with PAD. OBJECTIVE: To investigative whether a program that focuses on 8 major guideline-recommended risk-management therapies reduces cardiovascular and limb events in patients with PAD. DESIGN, SETTING AND PARTICIPANTS: An observational cohort study with up to 7 years of follow-up was conducted using data from administrative databases from Ontario, Canada, between July 1, 2004, and March 31, 2013. Patients with symptomatic PAD who were enrolled in the Systematic Assessment of Vascular Risk (SAVR) program at a single tertiary vascular center in Ontario between July 2004 and April 2007 were matched with up to 2 (control) patients with PAD from other Ontario tertiary vascular centers not enrolled in the program using propensity score methods. Cox proportional hazards regression analysis was used to compare outcomes. EXPOSURES: Program that promoted antiplatelet agents, statins, angiotensin-converting enzyme inhibitors, blood pressure control, lipid control, diabetic glycemic control, smoking cessation, and target body mass index by engaging vascular surgeons, family physicians, and patients with PAD. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite risk ratio of death, acute myocardial infarction, or ischemic stroke. Secondary outcomes included rates of lower limb amputations, bypass surgical procedures, and peripheral angioplasties with and without a stent. RESULTS: A total of 791 patients were studied after propensity score matching; the mean (SD) age of patients in the SAVR group (n = 290) was 67.9 (10.4) years and 68.2 (11.2) years in the control group (n = 501). During follow-up, the SAVR group experienced the primary outcome at a significantly lower rate than the control group (adjusted hazard ratio [HR], 0.63; 95% CI, 0.52-0.77). Patients in the SAVR group were also less likely to have major amputation (adjusted HR, 0.47; 95% CI, 0.29-0.77), minor amputation (adjusted HR, 0.26; 95% CI, 0.13-0.54), bypass surgery (adjusted HR, 0.47; 95% CI, 0.30-0.73), or hospitalization due to heart failure (adjusted HR, 0.73; 95% CI, 0.53-1.00). The rate of peripheral angioplasty with or without a stent was higher among the SAVR group (adjusted HR, 2.97; 95% CI, 2.15-4.10). CONCLUSIONS AND RELEVANCE: A guideline-recommended risk-reduction program targeted at patients with PAD was associated with fewer cardiovascular and limb events over the long-term. This finding emphasizes the need for well-designed prospective studies to develop and examine the effect of such programs on reducing PAD-related morbidity, mortality, and health care costs.

Area 5 influences excitability within the primary motor cortex in humans.

In non-human primates, Brodmann's area 5 (BA 5) has direct connectivity with primary motor cortex (M1), is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS), intermittent (iTBS), and sham theta-burst stimulation (sham TBS) over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations.

Influence of area 5 on interhemispheric inhibition.

Brodmann's area 5 is implicated in the sensorimotor control of hand movement in humans and nonhuman primates. However, little is known about the influence of area 5 on the neural circuitry within the primary motor cortex that underpins hand control. The present study investigated the neural circuitry of interhemispheric inhibition (IHI) that exists between homologous muscle representations in the motor cortex. Using paired-pulse transcranial magnetic stimulation, IHI was probed from the left-to-right hemisphere and vice versa for the first dorsal interosseous muscle of the hand at short (10 ms) and long (40 ms) latencies before and for up to 1 h after continuous θ-burst stimulation over left hemisphere area 5. The results indicate that continuous θ-burst over area 5 increases IHI at short latencies in the left hand (left-to-right inhibition) from 5-20 and 45-60 min after stimulation. Short latency inhibition in the right hand and bilateral long latency inhibition remain unaltered. The data indicate that area 5 influences the IHI that exists between the representations of the hand muscles. This effect occurs ipsilateral to the left area 5, suggesting that effects are mediated through changes in the excitability of transcallosal neurons originating in the left motor cortex.

Functional connectivity from area 5 to primary motor cortex via paired-pulse transcranial magnetic stimulation.

In non-human primates area 5 is dominated by the representation of the hand and forelimb, and has direct connectivity with primary motor cortex (M1) implicating its role in the control of hand movements. To date, few studies have investigated the function of area 5 in humans or its connectivity with M1. Using paired-pulse TMS, the present study investigates the functional connectivity between putative area 5 within the medial superior parietal lobule and ispilateral M1 in humans. Specifically, the motor evoked potential (MEP) from the first dorsal interosseous muscle of the right hand was quantified with and without conditioning TMS stimuli applied to left-hemisphere area 5. The timecourse of functional connectivity was examined during cutaneous stimulation applied to the thumb and index finger and also during rest whereby no somatosensory processing demands were imposed. Results indicate that area 5 facilitates and inhibits the MEP at 6 and 40ms, respectively, during somatosensory processing. No net influence of area 5 on M1 output was observed during rest. We conclude that area 5 has a task-dependent and temporally specific influence on M1 output, and suggest that the interaction between these areas presents a novel path with which to alter the motor output, and possibly movement of hand muscles.