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Biomedical subjects

Nicholas S Hill

Publications and source records attributed to Nicholas S Hill.

At least 19 recordsLinked to original sources
PubMed2006

Noninvasive ventilation for acute lung injury: how often should we try, how often should we fail?

The selection of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) to receive noninvasive ventilation (NIV) is challenging, partly because there are few reliable selection criteria. The study by Rana and colleagues in the previous issue of Critical Care identifies metabolic acidosis and a lower oxygenation index as predictors of NIV failure, although it is unable to identify threshold values. It also demonstrates that treating patients with NIV for ALI/ARDS and shock is an exercise in futility. Future studies need to focus on criteria that will enable selection of patients for whom NIV will have a high likelihood of success.

Humans↗
PubMed2006

Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension.

STUDY OBJECTIVES: Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hypertension (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition. DESIGN: Open-label study. SETTING: Medical ICUs of three tertiary care hospitals in New England. PATIENTS: Thirteen consecutive adult patients undergoing right-heart catheterization and a pulmonary vasodilator trial for the initial evaluation of PAH. INTERVENTIONS: Patients were administered inhaled nitric oxide (iNO), i.v. epoprostenol, and a 3-h infusion of BNP alone and 1 h after an oral dose of the phosphodiesterase-5 inhibitor sildenafil. RESULTS: iNO and sildenafil alone decreased mean pulmonary artery pressure (mPAP) without a significant fall in pulmonary vascular resistance (PVR). Epoprostenol decreased both mPAP and PVR. BNP alone had no significant effect on pulmonary hemodynamics, but the combination of sildenafil plus BNP decreased mPAP and PVR for up to 6 h after stopping BNP. The decrease in mPAP with sildenafil plus BNP (+/- SE) was greater than after 1 h of sildenafil alone (44.6 +/- 3.8 to 40.6 +/- 3.9 mm Hg, p = 0.027). An acute vasodilator response, defined as a decrease in mPAP > 10 mm Hg and end mPAP < 40 mm Hg, was seen in 0 of 8 patients with iNO, 1 of 13 patients with epoprostenol, 0 of 13 patients with BNP, and 4 of 12 patients with sildenafil plus BNP. BNP decreased mean systemic arterial pressure (5.6 +/- 2.8 mm Hg) but had no effect on cardiac output or systemic vascular resistance. CONCLUSIONS: A 3-h BNP infusion does not significantly improve pulmonary hemodynamics in most patients with PAH but is well tolerated and augments the acute pulmonary vasodilator effect of sildenafil.

Administration, Inhalation↗
PubMed2006

Utilization of noninvasive ventilation in acute care hospitals: a regional survey.

PURPOSES: Little information is available on the utilization of noninvasive positive-pressure ventilation (NPPV) in the United States. Accordingly, we performed a survey on the use of NPPV at acute care hospitals in a region of the United States to determine variations in utilization and between hospitals, the reasons for lower rates of utilization, and the techniques used for application. METHODS: Using survey methodology, we developed a questionnaire consisting of 19 questions and distributed it by mail to directors of respiratory care at all 82 acute care hospitals in Massachusetts and Rhode Island. Nonresponders were contacted by phone to complete the survey. Responses were analyzed using standard statistics, including t tests and Mann-Whitney U tests where appropriate. RESULTS: We obtained responses from 71 of the 82 hospitals (88%). The overall utilization rate for NPPV was 20% of ventilator starts, but we found enormous variation in the estimated utilization rates among different hospitals, from none to > 50%. The top two reasons given for lower utilization rates were a lack of physician knowledge and inadequate equipment. In the 19 hospitals that provided detailed information, COPD and congestive heart failure constituted 82% of the diagnoses of patients receiving NPPV, but NPPV was still used in only 33% of patients with these diagnoses receiving any form of mechanical ventilation. CONCLUSIONS: The utilization rates for NPPV vary enormously among different acute care hospitals within the same region. The perceived reasons for lower utilization rates include lack of physician knowledge, insufficient respiratory therapist training, and inadequate equipment. Educational programs directed at individual institutions may be useful to enhance utilization rates.

Emergency Service, Hospital↗
PubMed2006

Conversion to bosentan from prostacyclin infusion therapy in pulmonary arterial hypertension: a pilot study.

STUDY OBJECTIVES: We assessed the efficacy of bosentan in transitioning from prostacyclin infusions in patients with pulmonary arterial hypertension (PAH). METHODS: Twenty-two PAH patients were recruited from five PAH centers if they had been clinically stable while receiving therapy with IV epoprostenol or subcutaneous treprostinil for at least 3 months. Patients were observed in an open-label prospective trial while bosentan was added to therapy, and then epoprostenol or treprostinil were tapered after 2 months. RESULTS: Ten of the 22 patients were transitioned off prostacyclin infusion therapy after a mean (+/- SEM) duration of 6.1 +/- 1.2 months. Of those patients, seven patients have continued not receiving prostacyclin infusion therapy for a mean duration of 17.7 +/- 5.3 months, with no significant changes in pulmonary artery (PA) pressure estimated by echocardiography, World Health Organization (WHO)/New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD), or Borg dyspnea score. The conditions of three patients deteriorated, necessitating the resumption of prostacyclin therapy, and two patients subsequently died. Twelve patients failed to transition or even lower the prostacylin infusion rate and had worsening of their WHO/NYHA functional class and estimated systolic PA pressures, and had a trend toward deterioration in their mean 6MWD (294 +/- 41 to 198 +/- 34 m, respectively; p = 0.2). Of these, two patients subsequently died. The baseline characteristics of those who transitioned successfully vs those who transitioned unsuccessfully were a lower prostacyclin infusion rate, and less severe elevations in the mean and estimated systolic PA pressures. CONCLUSION: Transitioning from therapy with prostacyclin to bosentan is possible in some PAH patients, mainly in those receiving lower prostacyclin doses and having less pulmonary hypertension at baseline. Careful patient selection and close interim monitoring is needed because the conditions of patients can deteriorate, and they may not respond to the resumption of therapy with prostacyclin.

Administration, Oral↗
PubMed2006

Risk factors for extubation failure in patients following a successful spontaneous breathing trial.

BACKGROUND: To assess the factors associated with reintubation in patients who had successfully passed a spontaneous breathing trial. METHODS: We used logistic regression and recursive partitioning analyses of prospectively collected clinical data from adults admitted to ICUs of 37 hospitals in eight countries, who had undergone invasive mechanical ventilation for > 48 h and were deemed ready for extubation. RESULTS: Extubation failure occurred in 121 of the 900 patients (13.4%). The logistic regression analysis identified the following associations with reintubation: rapid shallow breathing index (RSBI) [odds ratio (OR), 1.009 per unit; 95% confidence interval (CI), 1.003 to 1.015]; positive fluid balance (OR, 1.70; 95% CI, 1.15 to 2.53); and pneumonia as the reason for initiating mechanical ventilation (OR, 1.77; 95% CI, 1.10 to 2.84). The recursive partitioning analysis allowed the separation of patients into different risk groups for extubation failure: (1) RSBI of > 57 breaths/L/min and positive fluid balance (OR, 3.0; 95% CI, 1.8 to 4.8); (2) RSBI of < 57 breaths/L/min and pneumonia as reason for mechanical ventilation (OR, 2.0; 95% CI, 1.1 to 3.6); (3) RSBI of > 57 breaths/L/min and negative fluid balance (OR, 1.4; 95% CI, 0.8 to 2.5); and (4) RSBI of < 57 breaths/L/min (OR, 1 [reference value]). CONCLUSIONS: Among routinely measured clinical variables, RSBI, positive fluid balance 24 h prior to extubation, and pneumonia at the initiation of ventilation were the best predictors of extubation failure. However, the combined predictive ability of these variables was weak.

Aged↗
PubMed2006

Pulmonary rehabilitation.

Pulmonary rehabilitation programs use multidisciplinary teams to optimize physical and social functioning of patients with chronic respiratory impairment. These programs provide rehabilitation in inpatient, outpatient, or home settings, using at least three sessions weekly (one may be unsupervised) for at least 6 wk. The programs usually consist of exercise training, education, and psychosocial/behavioral components. Upper extremity exercises and instruction on breathing technique are included in most rehabilitation programs and reduce dyspnea, but the contribution of these to improved functional capacity remains unproven. Decreases in the sensation of dyspnea, increased functional exercise capacity, and enhanced quality of life of patients with chronic obstructive pulmonary disease (COPD) are established benefits of pulmonary rehabilitation. Evidence is lacking for the efficacy of rehabilitation for patients with non-COPD causes of pulmonary impairment, but many of these patients probably benefit. Despite the availability of strong evidence to support the efficacy of pulmonary rehabilitation programs in patients with severe COPD, third-party reimbursement policies have been inconsistent. Nonetheless, enrollment in a pulmonary rehabilitation program is encouraged for all appropriate candidates with chronic respiratory impairment, particularly for those with severe COPD.

Exercise Therapy↗
PubMed2006

Neuromuscular disease in respiratory and critical care medicine.

Neuromuscular diseases that affect the respiratory system are a major cause of morbidity and mortality in both acute and long-term settings. This conference examined the pathophysiology and management of neuromuscular diseases in both settings. Presentations by experts representing respiratory, physiologic, pediatric, neurologic, and intensive-care disciplines covered a broad range of topics. This summary of the conference briefly describes the main points of each presentation and highlights areas that need addressing in the future. Major topics covered include the basic respiratory pathophysiology of neuromuscular disease; respiratory complications and management of amyotrophic lateral sclerosis; techniques of noninvasive ventilation and secretion removal; and evaluation and management of neuromuscular-induced respiratory failure in the acute-care setting, including Guillain-Barré syndrome, myasthenic crisis, and critical-illness myoneuropathy.

Airway Obstruction↗
PubMed2005

Role of 12-lipoxygenase in hypoxia-induced rat pulmonary artery smooth muscle cell proliferation.

The 12-lipoxygenase (12-LO) pathway of arachidonic acid metabolism stimulates cell growth and metastasis of various cancer cells and the 12-LO metabolite, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], enhances proliferation of aortic smooth muscle cells (SMCs). However, pulmonary vascular effects of 12-LO have not been previously studied. We sought evidence for a role of 12-LO and 12(S)-HETE in the development of hypoxia-induced pulmonary hypertension. We found that 12-LO gene and protein expression is elevated in lung homogenates of rats exposed to chronic hypoxia. Immunohistochemical staining with a 12-LO antibody revealed intense staining in endothelial cells of large pulmonary arteries, SMCs (and possibly endothelial cells) of medium and small-size pulmonary arteries and in alveolar walls of hypoxic lungs. 12-LO protein expression was increased in hypoxic cultured rat pulmonary artery SMCs. 12(S)-HETE at concentrations as low as 10(-5) microM stimulated proliferation of pulmonary artery SMCs. 12(S)-HETE induced ERK 1/ERK 2 phosphorylation but had no effect on p38 kinase expression as assessed by Western blotting. 12(S)-HETE-stimulated SMC proliferation was blocked by the MEK inhibitor PD-98059, but not by the p38 MAPK inhibitor SB-202190. Hypoxia (3%)-stimulated pulmonary artery SMC proliferation was blocked by both U0126, a MEK inhibitor, and baicalein, an inhibitor of 12-LO. We conclude that 12-LO and its product, 12(S)-HETE, are important intermediates in hypoxia-induced pulmonary artery SMC proliferation and may participate in hypoxia-induced pulmonary hypertension.

Animals↗
PubMed2005

Retinoids and pulmonary hypertension.

BACKGROUND: Retinoic acid has antimitogenic effects on smooth muscle cells. Studies on the systemic circulation suggest that it may reduce vascular thickening. Relationships between retinoids and pulmonary hypertension/pulmonary vascular remodeling, however, have not been explored. Thus, the present study examined retinoid levels in plasma of patients with idiopathic pulmonary arterial hypertension and the effects of retinoic acid on human pulmonary artery smooth muscle cell growth. METHODS AND RESULTS: We measured retinoid levels by gas chromatograph-mass spectrometer technique in plasma of idiopathic pulmonary arterial hypertension patients and in age- and sex-matched healthy control subjects. Patients had significantly lower levels of all-trans retinoic acid and 13-cis retinoic acid than control subjects but similar 9-cis retinoic acid and retinol levels. In cultured human pulmonary artery smooth muscle cells, all-trans retinoic acid suppressed serotonin-induced cell growth. These cells were found to express the retinoid acid receptors RARalpha, RARbeta, RARgamma, RXRalpha, and RXRbeta. Gene array analysis showed that retinoic acid induces the expression of GADD45A, a known cell growth suppressor. Contrary to expectations, plasma from pulmonary hypertension patients suppressed cell growth, likely influenced by factors other than retinoids. CONCLUSIONS: Idiopathic pulmonary arterial hypertension patients have reduced retinoic acid levels, and retinoic acid treatment can elicit growth-inhibitory signals in pulmonary artery smooth muscle cells in vitro. Thus, retinoic acid may influence pulmonary vascular remodeling in humans.

Adult↗
PubMed2005

Pulmonary hypertension: inhaled nitric oxide, sildenafil and natriuretic peptides.

Phosphodiesterase-5 (PDE5) inhibitors and other agents that modulate intracellular cGMP are now emerging as promising, safe, and easy to administer therapies for pulmonary hypertension, with relatively few side effects. Recent studies have shown that PDE5 inhibitors are potent acute pulmonary vasodilators in experimental models that partially reverse established pulmonary arterial hypertension and blunt chronic pulmonary hypertension. In addition, studies on animals reveal that PDE5 inhibitors work in concert with nitric oxide and/or natriuretic peptide levels by enhancing intracellular cGMP and cGMP-mediated vasodilator effects. Further, the combination of PDE5 inhibitors and agents that increase cGMP or cAMP also yields additive beneficial effects on pulmonary hemodynamics in patients with pulmonary arterial hypertension.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension.

Sildenafil and inhaled nitric oxide (iNO) relax smooth muscle by inhibiting the degradation and stimulating the production of cyclic guanosine monophosphate, respectively. We compared the acute pulmonary vasodilator effects of sildenafil, iNO, and epoprostenol and asked whether the combination of iNO with sildenafil had additive pulmonary vasodilator effects. We assessed the effects of extended use of sildenafil in a small cohort of patients. Twenty patients with pulmonary arterial hypertension underwent an acute vasodilator trial with sildenafil (all patients), iNO and iNO plus sildenafil (11), and epoprostenol (19). We also provided sildenafil to patients who were ineligible for, or had clinical deterioration on epoprostenol, treprostinil, or bosentan. Mean+/-se pulmonary artery pressure dropped by 13+/-3%, 19+/-4%, 14+/-3%, and 26+/-4% with epoprostenol, iNO, sildenafil, and iNO+sildenafil, respectively. Cardiac index increased with epoprostenol and sildenafil. A correlation was found between the effects of iNO and epoprostenol. Nine out of ten patients who were started on long-term sildenafil treatment alone or in combination with other vasodilators had symptomatic improvement. Three died of right heart failure. In conclusion, sildenafil is a potent acute pulmonary vasodilator, an effect that is potentiated by combination with iNO. Long-term therapy of pulmonary hypertension with sildenafil alone or in combination with other agents appears to be safe and well tolerated.

Administration, Inhalation↗
PubMed2005

Sleep in restrictive and neuromuscular respiratory disorders.

Thoracic restrictive disorders (i.e., chest wall deformities or neuromuscular diseases), may predispose to sleep-disordered breathing, poor sleep quality, and nocturnal hypoventilation. These disorders intensify the effects of reductions in both respiratory center output and central chemosensitivity and increases in upper airway resistance that occur with the onset of sleep. Normally, rapid eye movement (REM) sleep suppresses the activity of nondiaphragmatic breathing muscles, further reducing ventilation. Diaphragmatic or upper airway muscle weakness and reduced chest wall compliance in patients with thoracic restrictive disorders enhance the severity of sleep-disordered breathing during REM sleep, worsening gas exchange abnormalities and sleep fragmentation and impairing daytime functioning. Although daytime respiratory function and nocturnal oxygen saturation are not well correlated, some markers may be useful for identifying patients with thoracic restriction at risk for sleep-disordered breathing. Although some patients may respond to continuous positive airway pressure (CPAP) alone, noninvasive positive pressure ventilation (NPPV) is a more important part of disease management for patients with restrictive thoracic disorders. This technique improves nocturnal ventilation and sleep quality but may also contribute to sleep fragmentation in some patients. If the patient is an unsuitable candidate for or fails NPPV, tracheostomy mechanical ventilation should be considered.

Contraindications↗
PubMed2005

Noninvasive ventilation for acute respiratory failure.

PURPOSE OF REVIEW: This review critically examines recent literature related to applications of noninvasive ventilation in the acute setting. RECENT FINDINGS: Recent articles have strengthened the evidence supporting the use of noninvasive ventilation for patients with cardiogenic pulmonary edema and exacerbation of severe chronic pulmonary obstructive disease. In the former, however, it remains unclear whether noninvasive ventilation offers any significant advantages over continuous positive airway pressure. The rate of myocardial infarction seems to be no higher when patients with cardiogenic pulmonary edema are treated with noninvasive ventilation rather than continuous positive airway pressure, although caution is still advised in patients with acute coronary syndromes. Noninvasive ventilation also does not seem to increase the risk of dissemination of severe acute respiratory syndrome to health care workers as long as strict isolation procedures are used. Noninvasive ventilation facilitates weaning in patients with chronic obstructive pulmonary disease but should not be used routinely to treat extubation failure, and necessary intubation should not be delayed. Guidelines for the use of noninvasive ventilation can alter caregivers' behavior but have not been clearly shown to improve outcomes. Outcomes do seem to improve, however, as caregivers acquire experience with the technique. SUMMARY: The recent literature has refined some of the current indications for noninvasive ventilation in the acute-care setting, including chronic pulmonary obstructive disease and cardiogenic pulmonary edema. Guidelines for use are now being developed, and outcomes seem to be improving, partly as a consequence of greater caregiver experience and possibly related to technologic advances.

Acute Disease↗
PubMed2005

Noninvasive positive-pressure ventilation to treat hypercapnic coma secondary to respiratory failure.

INTRODUCTION: Hypercapnic coma secondary to acute respiratory failure (ARF) is considered to be a contraindication to the use of treatment with noninvasive positive-pressure ventilation (NPPV). However, intubation exposes these patients to the risk of complications such as nosocomial pneumonia, sepsis, and even death. PATIENTS AND METHODS: We performed a prospective, open, noncontrolled study to assess the outcomes of NPPV therapy in patients with a Glasgow coma scale (GCS) score of </= 8 points due to ARF. The primary goal of the study was to determine the success of NPPV therapy (defined as a response to therapy allowing the patient to avoid endotracheal intubation, and to survive a stay in the ICU and at least 24 h on a medical ward) in patients with hypercapnic coma, compared to those who started NPPV therapy while awake. The secondary goal of the study was to identify the variables that can predict a failure of NPPV therapy in these patients. RESULTS: A total of 76 coma patients (80%) responded to NPPV therapy, and 605 patients with GCS scores > 8 responded to therapy (70%; p = 0.04). A total of 25 coma patients died in the hospital (26.3%), and 287 noncoma patients died in the hospital (33.2%; p = 0.17). The variables related to the success of NPPV therapy were GCS score 1 h posttherapy (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.53 to 3.53) and higher levels of multiorgan dysfunction, as measured by the maximum sequential organ failure assessment index score reached during NPPV therapy (OR, 0.72; 95% CI, 0.55 to 0.92). CONCLUSIONS: We concluded that selected patients with hypercapnic coma secondary to ARF can be treated as successfully with NPPV as awake patients with ARF.

APACHE↗