Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial.

CONTEXT: Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC). OBJECTIVE: To determine whether inhaled nitric oxide gas reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008. Intervention Inhaled nitric oxide gas vs inhaled nitrogen placebo. MAIN OUTCOME MEASURES: The primary end point was the time to resolution of painful crisis, defined by (1) freedom from parenteral opioid use for 5 hours; (2) pain relief as assessed by visual analog pain scale scores of 6 cm or lower (on 0-10 scale); (3) ability to walk; and (4) patient's and family's decision, with physician consensus, that the remaining pain could be managed at home. RESULTS: There was no significant change in the primary end point between the nitric oxide and placebo groups, with a median time to resolution of crisis of 73.0 hours (95% confidence interval [CI], 46.0-91.0) and 65.5 hours (95% CI, 48.1-84.0), respectively (P = .87). There were no significant differences in secondary outcome measures, including length of hospitalization, visual analog pain scale scores, cumulative opioid usage, and rate of acute chest syndrome. Inhaled nitric oxide was well tolerated, with no increase in serious adverse events. Increases in venous methemoglobin concentration confirmed adherence and randomization but did not exceed 5% in any study participant. Significant increases in plasma nitrate occurred in the treatment group, but there were no observed increases in plasma or whole blood nitrite. CONCLUSION: Among patients with SCD hospitalized with VOC, the use of inhaled nitric oxide compared with placebo did not improve time to crisis resolution. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00094887.

Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study.

In addition to vaso-occlusion by sickled erythrocytes, the pathophysiology of sickle cell disease (SCD) is compounded by the diminished bioavailability of nitric oxide (NO), associated with vasoconstriction, endothelial activation and cell adhesion. We tested the ability of sodium nitrite, which can be converted to NO by deoxyhaemoglobin at acid pH and low oxygen tension, to improve blood flow in patients with SCD. In a phase I/II clinical trial, sodium nitroprusside, NG-monomethyl-L-arginine, and sodium nitrite were infused sequentially into the brachial artery in 14 patients at steady state. In a dose-dependent manner, sodium nitrite infusion rates of 0.4, 4 and 40 micromol/min into the brachial artery augmented mean venous plasma nitrite concentrations (P < 0.0001) and stimulated forearm blood flow up to 77 +/- 11% above baseline (P < 0.0001), measured by venous occlusion strain gauge plethysmography. This nitrite response was blunted significantly compared to controls without SCD, as previously seen with other NO donors. Sodium nitrite infusions were well tolerated without hypotension, clinically significant methaemoglobinaemia or other untoward events. The unique pharmacological properties of nitrite as a hypoxia-potentiated vasodilator and cytoprotective agent in the setting of ischaemia-reperfusion injury make this anion a plausible NO donor for future clinical trials in SCD.

Quality Improvement Training in a Variety of Cancer Care Delivery Settings: Experiences From a Comprehensive Cancer Center, an Academic Medical Center, and Community Practices.

PURPOSE: Training clinical and supportive staff in quality improvement (QI) theory and use of QI tools has the potential to improve oncology care delivery. We report our combined experience of providing training to oncologists in a variety of local settings and assess the effect of the training on individual participants and for institutions. METHODS: Multidisciplinary oncology teams at a comprehensive cancer center, an academic medical center, and community practices were led through experiential QI training that spanned several months. The curriculum included didactic training sessions that attendees applied to their local project-based work and that required plan-do-study-act cycles. The curriculum was adapted to the smaller practice setting through use of a workbook and a reduced focus on quantitative methods. All teams were supported by coaches and provided final presentations to leadership. The self-rated abilities of trainees to use 15 QI tools were assessed with a pre/post training survey that had five response categories (information, skill, knowledge, understanding, and wisdom). Local institutional and external project presentations were tracked. RESULTS: During 7 years, 129 trainees participated in 56 QI projects. All of the 15 QI tools had 80% of trainees rate themselves in the top three categories (knowledge, understanding, and wisdom) after the training; none met this threshold before. Multiple projects were presented in institutional and external settings. Most projects targeted three of the four domains of the ASCO Quality Oncology Practice Initiative certification program standards. CONCLUSIONS: We implemented and sustained QI training programs in a variety of cancer delivery settings. The flexible training model should be easily adoptable by others.