nitric oxide on neonatal transport

dawngloves, BSN, RN · Mar 17, 2004

Make sure the tank isn't leaking or you 'll be one goofy crew! :chuckle

Sorry! Can't say I have any experience in trasporting pts on NO.

psychomachia · Mar 17, 2004

Here is an article from the Air Medical Journal - Jan/Feb 2004 issue (minus the pictures). E-mail me at [email protected] and I'll send you a .pdf file with the pictures (it was too large to upload in this reply)

Transporting neonates with nitric oxide

The 5-year ShandsCair experience

Nate M. Jesse1 [MEDLINE LOOKUP]

Lynn Drury [MEDLINE LOOKUP]

Michael D. Weiss, MD [MEDLINE LOOKUP]

Sections

Abstract

ShandsCair flight program and NO transports

NO transport protocol

Safety and NO transports

Patient population, response to NO, and outcomes

Conclusion

References

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Abstract TOP

Traditionally, hypoxic respiratory failure in the newborn has been treated with supplemental oxygen, conventional mechanical ventilation, sedation, and high-frequency oscillatory ventilation. Despite appropriate management with these treatment modes, care for critically ill newborns often requires more invasive measures, including extracorporeal membrane oxygenation (ECMO). Although it may be life saving, ECMO requires cannulation and anticoagulation, which introduces significant risk of morbidity.

ECMO is not offered in most institutions that care for sick neonates.

INOvent Transport Delivery System

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With that in mind, the advent of nitric oxide (NO) offers clinicians a valuable treatment option and a bridge from traditional therapies to ECMO. NO is a colorless, highly diffusible gas with a half-life of 6 to 10 seconds and a density the same as that of air.1 NO is present in the environment as a noxious chemical in such everyday pollutants as cigarette smoke and automobile exhaust.1 The medical properties of NO were not realized until 1987 when it was identified as the compound (or a major component of the compound) endothelial-derived relaxing factor (EDRF),2,3 which had been shown to cause vascular relaxation.4

The first use of NO to treat persistent pulmonary hypertension of the newborn (PPHN) was reported in 1992 by Roberts and colleagues and Kinesella et al.5,6 Since these first studies, numerous others have demonstrated the safety and efficacy of NO therapy for PPHN treatment.7-9 These studies led to Food and Drug Administration (FDA) approval of NO in 1999 for PPHN and its use by many centers without ECMO. This widespread use has necessitated using NO during transport of some neonates to ECMO centers. Because the abrupt cessation of NO before initiation of ECMO has been associated with significant, potentially life-threatening decreases in oxygenation,9 NO should not be discontinued until a seamless transition to ECMO can be ensured.

The environmental safety and efficacy of NO use during transports was documented in the literature in 2 small studies.10,11 Our program, a tertiary care ECMO referral center, began transporting with NO in 1998. This article reviews our 5-year experience with NO transports, highlighting our program, transport equipment and protocol, safety, patient population, response to NO, and outcomes.

ShandsCair flight program and NO transports TOP

The neonatal/pediatric transport team at ShandsCair performs more than 500 transports per year. The program uses multiple transport modes, including fixed-wing and rotor-wing aircraft and ground ambulances. Fixed-wing assets include a Cessna Citation Jet that flies about 40 transports per year (8% of total transports). Approximately 100 transports per year (21% of total transports) are performed in a Dauphin N1 rotor-wing aircraft. Ground transports are performed in 2 dedicated neonatal ambulances, a 2002 Ford F350 and a 2003 International; 354 ground transports are performed per year (71% of total transports).

The ShandsCair flight program is based at Shands Teaching Hospital at the University of Florida. The neonatal ICU is a level 3 ECMO center with facilities for up to 3 ECMO beds. The patient population in our NICU is made up of 60% referrals and 40% inborn. The referral base comprises north-central Florida and south Georgia. Since 1998, we have performed 78 NO transports. This type of mission accounts for about 5% of transports per year.

The ShandsCair flight program uses the INOvent transport system shown on the first page for NO dispersal and monitoring during transports. The system continuously monitors oxygen, NO, and nitrogen dioxide using an electrochemical cell and has a longer battery life than the standard INOvent system (up to 3 hours vs 30 minutes). The system operates with "D" cylinders that contain 353 L (800 ppm of NO in N2) with a filling pressure of 2000 pounds per square inch gauge. The transport system without the cylinders weighs 21 kg (46.2 pounds). This weight is an issue during rotor-wing flights and the loading and unloading of a transport isolette with INOvent added.

An alternate to INOvent is the aeroNOx delivery system manufactured by PulmoNOx. This system has FDA approval for use with the INOmax "D" cylinders. The system weighs only 5 kg (10 pounds). It has a battery life of up to 6 hours. It monitors oxygen, NO, and nitrogen dioxide.

NO transport protocol TOP

Given the extra weight and equipment involved, we developed the following criteria to designate a NO transport and initiate NO use by the team:

NO already has been started at the referring hospital.

Hypoxic respiratory failure of unknown etiology occurs in a neonate 34 weeks or older with an oxygen index (OI) of 20. The OI is calculated as follows: (fraction of inspired oxygen × mean airway pressure × 100)/postductal PaO2.12 The OI provides an objective measurement of respiratory failure with values of 30 to 40 indicative of severe respiratory distress.13

The transport team initiates the use of NO only after discussion with the attending neonatal physician. The same protocols as those for NICU inpatients are used.

The transport team documents the response to NO therapy. It is critical that saturations before and after NO therapy initiation are noted to gauge any response to the therapy.

If initiated during transport, NO will be given for the duration of the transport, regardless of the response.

The decision to start NO therapy, if it has not been started at the referring hospital, is made by the on-call attending physician. The decision is based on our in-house NO protocol criteria, which are as follows:

Institute NO at 20 parts per million (ppm) if PPHN is documented by echocardiogram in hospitalized patients or by preductal/postductal saturation difference of 8% in transport patients and OI > 25. If OI does not drop by 5 after 30 minutes, increase NO to 40 ppm.

Because OI values are difficult to obtain during a transport or not enough time is available to wait 30 minutes at a referring hospital, the NO is increased to 40 ppm if the neonate does not show a clinical response, as evidenced by a decrease in the pre-and postductal saturation differences (if present) or an improvement in saturations. NO is continued at this dose for the remainder of the transport.

Safety and NO transports TOP

NO is classified as a Division 2.2 agent (nonflammable, nonpoisonous compressed gas). The Federal Aviation Administration has not established national guidelines for inhaled NO during transports. When we began our program, we contacted our Federal Aviation Administration regional office for guidelines. Our program keeps a current material safety data sheet on file in our dispatch. The pilot/driver and dispatch are notified when NO will be taken on a transport. The dispatch center tracks the location of all transport vehicles; if an accident occurs, the center notifies the responding authorities that NO was on board the vehicle.

The Occupational Safety and Health Administration has set environmental exposure limits for NO at 25 ppm time-weighted average for 8 hours and 5 ppm limit for NO2 with excursions (ie, transient exposures) to 100 ppm.11,14 In most environments this is not a major concern to the health care team. However, during a transport the crew is confined to a limited area with poor air turnover.

Kinsella et al11 addressed these concerns. In that report, NO was bled directly into the transport vehicle at 40 ppm, with a continuous flow of 100% oxygen at 20 liters per minute. The environmental NO then was measured at 1, 30, and 60 minutes in various transport vehicles, including a King Air 200, King Air 90, Lear 35, ground ambulance, and Eurocopter A-Star with and without air exchange. In both cases, the amount of NO in the environment was very low calculations then were performed to simulate a worst case scenario: the catastrophic release of the entire "D" cylinder into the transport vehicle with no air exchange. Results showed that the calculated levels of NO were in the 25 to 40 ppm range for all fixed-wing aircraft and the ambulance, whereas the level of NO rose to 94 ppm in the Eurocopter A-Star. On the basis of these data, the authors concluded that NO and NO2 concentrations remain within safe ranges during transport with NO therapy.11

Patient population, response to NO, and outcomes TOP

The largest series in the literature reported to date involved only 25 NO transports.6 Of the 78 patients we have transported, 56 have been moved by helicopter, 16 by ground ambulance, and 6 by fixed-wing aircraft. This, to our knowledge, is the largest series of NO transports by helicopter. A breakdown of patient demographics by diagnosis and transports per year is summarized in Table 1 and Figure 1. NO flights per year has increased steadily since 1998. Patients with a diagnosis of PPHN without meconium aspiration syndrome accounted for 76% of our total NO flights.

No major complications (such as death, nitrogen dioxide generation, delivery system problems) have occurred during the transport of any of these neonates.

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Table. Patients Transported with Nitric Oxide (n = 78)

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Persistent pulmonary hypertension of newborn 36 (50%)*

Meconium aspiration syndrome 23 (57%)

Congenital diaphragmatic hernia 2 (50%)

Respiratory distress syndrome 12 (17%)

Congenital heart disease 2 (100%)

Hypoplastic lungs 1 (0%)

Adult respiratory distress syndrome 1 (0%)

Pneumonia 1 (0%)

*Figures in parentheses represent percentage of patients who went on to require ECMO therapy.

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Figure 1. Nitric Oxide transports per year through December 2002. Year periods are defined as July to July. The last data set only represents half a year of data. Solid black bars represent the number the total number of transports in which NO was taken. The hatched bars represent the number of transports in which NO was taken and used.

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Thirty-one patients had complete medical records from which alveolar-arterial (A-a) gradients could be calculated at the time of referral and on arrival to our facility. Twenty-two had a decrease in their A-a gradient from 608 ± 31 to 550 ± 63; the remaining 9 had an increase in the A-a gradient from 523 ± 77 to 591 ± 74. These results differ from those reported in the literature in that not all patients had improved oxygenation.11 Thirty-six of 78 patients went on to require ECMO therapy at a median time of 2.75 hours (range 1.25-93 hours) after NO initiation.

Conclusion TOP

Based on our 78 experiences in 5 years, NO therapy is a safe mode for the stabilization and transport of critically ill neonates. With the increase in non-ECMO centers using NO, this technology allows therapy to continue during transport to an ECMO center, preventing potential patient compromise. Based on our limited data and experience, we recommend early transfer of neonates to an ECMO center once NO therapy is initiated if the patient does not have an immediate and sustained response.

References TOP

1. Holowaty L. Nitric oxide. Neonatal Netw 1995;14:83-86.MEDLINE

2. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 1987;84:9265-9269.MEDLINE

3. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524-526.MEDLINE

CROSSREF

4. Furghott R, Zawadki J. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetocholine. Nature 1980;288:373-376.MEDLINE

5. Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:819-820.MEDLINE

CROSSREF

6. Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:818-819.MEDLINE

CROSSREF

7. The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997;336:597-604.MEDLINE

CROSSREF

8. Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, et al. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn Clinical Inhaled Nitric Oxide Research Group. N Engl J Med 2000;342:469-474.MEDLINE

CROSSREF

9. Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, et al. Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn. Pediatrics 1999;104:231-236.MEDLINE

10. Kinsella JP, Schmidt JM, Griebel J, Abman SH. Inhaled nitric oxide treatment for stabilization and emergency medical transport of critically ill newborns and infants. Pediatrics 1995;95:773-776.MEDLINE

11. Kinsella JP, Griebel J, Schmidt JM, Abman SH. Use of inhaled nitric oxide during interhospital transport of newborns with hypoxemic respiratory failure. Pediatrics 2002;109:158-161.MEDLINE

12. Torosian MB, Statter MB, Arensman RM. Extracorporeal membrane oxygenation, W.B. Saunders, Philadelphia 1988.

13. Gamella TL. Neonatology: management, procedures, on-call problems, diseases, and drugs, Lange Medical Books, New York 1999.

14. Prevention CfDCa. Recommendations for occupational safety and health standards. MMWR Morb Mortal Wkly Rep 1998;37:s7-s21.

Publishing and Reprint Information TOP

1Nate M. Jesse works in the department of pediatrics at the University of Florida in Gainesville. Lynn Drury works in the ShandsCair flight program in Gainesville. Michael D. Weiss, MD, works in both the department and the flight program.

doi:10.1016/j.amj.2003.10.001

debtransrn · Mar 18, 2004

Thanks for the info- I'm sure it will help!

prmenrs, RN · Mar 18, 2004

WOW! Thank you, psychomachia. Good article.