2005 OPEN FORUM Abstracts
INHALED NITRIC OXIDE: FIVE-YEAR EXPERIENCE WITH A PROTOCOL FOR APPROPRIATE USE.
Dean R. Hess PhD RRT FAARC, Luca M. Bigatello MD, B Taylor Thompson MD, Daniel W. Chipman RRT, Robert M. Kacmarek PhD RRT FAARC. Massachusetts General Hospital and Harvard Medical School, Boston MA.
Background: Randomized controlled trials have reported benefit for the use of inhaled nitric oxide (iNO) in the care of term newborns with hypoxic respiratory failure and the FDA approved the use of iNO for this indication on December 23, 1999. Because high level evidence for off-label use of iNO is lacking and due to the expense associated with its use, we developed an institution-approval protocol for use of iNO based on lower levels of evidence and consensus.
Methods: Use of iNO is controlled by our Innovative Devices and Therapeutics Committee and is monitored under the auspices of a Phase IV observational study with IRB approval. Institutional use of iNO was initially approved for hypoxic respiratory failure in newborns, acute right ventricular failure, severe acute respiratory distress syndrome (ARDS), inhalation injury, post lung resection surgery, post heart or lung transplantation, and short term use to test pulmonary vascular reactivity (added after year 3). Specific eligibility criteria were established by consensus. If criteria to initiate therapy are met, a short trial is conducted and a decision to continue therapy is based on strict acute-response criteria. The respiratory care department is charged with screening all requests for use of iNO, determining eligibility based on institution-approved criteria, dispensing the gas, monitoring all aspects of its utilization, and maintaining a database of its use and efficacy. Every request for iNO is prospectively reviewed by one of the respiratory care department management team before treatment is initiated. Requests that fall outside approved criteria are mediated by the physician co-chairs of the Critical Care Committee. The protocol was implemented on April 1, 2000, and we report here the experience of the first 5 years.
Results: From April 1, 2000, until April 1, 2005, 671 trials of iNO were conducted (576 patients); 96% met eligibility criteria. iNO was continued in 465 trials (408 patients); 94% met criteria to continue. For those who did not meet eligibility requirements, iNO use was approved after respiratory care and physician mediation. For the 5-year period, there were a total of 1,707 days of therapy, median duration of therapy was 2.2 days (IQR 0.9 to 4.2 days, maximum 48 days), and the total cost of therapy was $3,162,859. The distribution of iNO trials was 150 (19.4%) for term newborns, 27 (3.5%) for premature newborns, 279 (36%) for acute right ventricular failure, 77 (10%) for ARDS, 94 (12.4%) to test pulmonary vascular reactivity, 17 (2.2%) post transplant, 12 (1.6%) for inhalation injury, 12 (2.3%) post lung resection surgery, and 3 (0.4%) for sickle cell crisis. No safety concerns have arisen. 99% of methemoglobin results were £ 3%; 2 results were > 5% (5.7% and 7%) - in both cases the NO dose was 80 ppm and methemoglobin decreased to < 3% with a reduction in NO dose. There were no cases of excessive NO2 concentration. For this 5 yr period, 16 problems were reported related to the INOvent delivery system (0.26 per 28 days of use); all were minor in nature - none was serious and none adversely affected patient care.
Conclusions: The greatest use of iNO at our hospital is off-label. We have had > 90% compliance with this institutional protocol for off-label use suggesting that we have been able, for the most part, to control the appropriate use of iNO within institutional guidelines. No serious adverse events occurred related to iNO therapy. The delivery system is robust. We continue to monitor closely the use of iNO in which we audit each use of this therapy.