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R M Kacmarek

Publications and source records attributed to R M Kacmarek.

At least 37 records · Page 2Linked to original sources

Nitric oxide delivery during high-frequency oscillatory ventilation.

BACKGROUND: Inhaled nitric oxide (NO) is used increasingly in the care of infants with hypoxemic respiratory failure and is frequently combined with high-frequency oscillation (HFO). The aim of this study was to evaluate delivery of NO during HFO using titration into the ventilator circuit or using the INOvent Delivery System. METHODS: NO was delivered into the HFO circuit at three sites (pre-humidifier, post-humidifier, and after the bellows) by continuous titration using a rotameter. The target NO concentration ([NO]) was initially adjusted using a rapid-response chemiluminescence NO analyzer without oscillation at 5, 10, and 20 parts per million (ppm). During the study, gas was sampled 5 cm from the bellows (proximal), 35 cm from the bellows (middle), and at the distal end of the circuit (distal). The ventilator was set at frequencies of 5, 10, and 15 Hz, mean airway pressures of 15, 20, and 25 cm H(2)O, and amplitudes of 20, 30, and 40 cm H(2)O. Soft and hard circuits were evaluated. The fraction of inspired oxygen was 0. 90, the inspiratory time fraction was 33%, and the bias flow was 20 L/min throughout the study. An INOvent Delivery System was also evaluated with the same HFO settings. RESULTS: The fluctuation of [NO] was minimal with continuous titration pre-humidifier at all HFO settings. [NO] fluctuated with titration post-humidifier and after the bellows, especially at the proximal sampling site. At the lung model, however, fluctuation of [NO] was always < 1.5 ppm and usually < 1 ppm. Delivered [NO] was lower than target [NO] with injection after the bellows (> 5%). The soft circuit showed better mixing of NO than the hard circuit. The INOvent Delivery System delivered a stable and accurate [NO] at all settings. [NO(2)] was < 1 ppm at all settings. CONCLUSIONS: Mixing of NO during HFO was acceptable at all the injection sites evaluated, although injection pre-humidifier was preferable because of small fluctuations of [NO]. The INOvent Delivery System was simple to use and delivered an accurate and precise [NO] during HFO.

Administration, Inhalation↗

Pressure support and pressure assist/control: are there differences? An evaluation of the newest intensive care unit ventilators.

BACKGROUND: Pressure support (PS) has been widely studied in both patients and lung models, but there is little data available evaluating pressure assist/control (P A/C, frequently referred to as PCV) and no data comparing the operational capabilities of these two modes on the newest generation of ICU ventilators. We used a spontaneously breathing lung model to evaluate the response of the following new generation ventilators to varying inspiratory demand in both PS and P A/C: Bear 1000, Dräger Evita 4, Hamilton Galileo, Nellcor Puritan-Bennett 840 and 740, Siemens Servo 300A, TBird AVS. METHODS: A bellows-in-a-box lung model was set at a respiratory rate of 12 breaths/min, inspiratory time of 1.0 second, and peak inspiratory flows (modified square wave) of 40, 60, and 80 L/min. Each ventilator was set at three levels of PS and P A/C: 10, 15, and 20 cm H(2)O. On all ventilators, flow-triggering was set as sensitive as possible without causing self-triggering. RESULTS: Trigger pressure, trigger pressure-time product, inspiratory trigger time delay, ventilator-delivered peak flow, inspiratory area as a percent of the ideal inspiratory area, expiratory time delay, supraplateau expiratory pressure change, and expiratory area all varied among ventilators and at different lung model peak flows (p < 0.01 and >/= 10% difference). However, PS and P A/C on a given ventilator only differed with regard to expiratory variables (p < 0. 01 and >/= 10% difference). CONCLUSION: In a given ventilator little difference exists in gas delivery and response variables between PS and P A/C, but performance differences do exist among the ventilators evaluated. Ventilator performance is diminished at high lung model peak flows and low pressure settings. (I)), whereas PS gives control over ending inspiration to the patient. What has not been clearly defined is the gas delivery and ventilator response differences, if any, between these two (PS and P A/C) pressure targeted assist modes. Most new generation intensive care unit (ICU) ventilators provide both pressure support (PS) and pressure assist/control (P A/C) ventilation.19,20 The specific operational difference between these two modes is the mechanism that transitions inspiration to expiration. With pressure support the primary mechanism is a decrease in peak inspiratory flow to a predetermined level, whereas with P A/C mechanical T(I) is preset.19,20 We compared the operation of seven of the newest generation ICU ventilators in a spontaneously breathing lung model in both PS and P A/C. We hypothesized that there would be no difference in variables assessed between PS and P A/C except for the transition to expiration and that there would be no difference in response among ventilators evaluated.

Equipment Safety↗

Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome.

BACKGROUND: Despite intensive research, there are no universally accepted clinical definitions for acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment. However, this definition may not reflect the true prevalence, severity and prognosis of these syndromes. METHODS: During a 22-month period, 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [arterial oxygen tension/fractional inspired oxygen (PaO(2)/FIO(2) </= 200 mmHg regardless of the level of positive end-expiratory pressure (PEEP), bilateral pulmonary infiltrates, and no evidence of left heart failure] were admitted into the intensive care units (ICU) of the Hospital del Pino, Las Palmas, Spain, and prospectively studied. The diagnosis of ALI and ARDS was made by a PEEP-FIO(2) trial, 24 h after patients met the Consensus inclusion criteria. Patients were classified as having ALI(-24 h) if the PaO(2)/FIO(2) was > 150 mmHg with PEEP = 5 cmH(2)O, and ARDS(-24 h) if the PaO(2) /FIO(2) was </= 150 mmHg with PEEP >/= 5 cmH(2)O. RESULTS: Overall mortality was 43 % (24 of 56). However, 24 h after inclusion, PaO(2) response to PEEP 5 cmH(2)O allowed the separation of our patients into two different groups: 31 patients met our ALI(-24 h) criteria (PaO(2)/FIO(2) > 150 mmHg) and their mortality was 22.6 %; 25 patients met our ARDS(-24 h) criteria (PaO(2)/FIO(2) </= 150 mmHg) and their mortality was 68 % (p = 0.0016). The differences in the respiratory severity index during the first 24 h of inclusion, PaO(2)/FIO(2) ratio at baseline and at 24 h, maximum plateau airway pressure, maximum level of PEEP, and number of organ system failures during the ICU stay were statistically significant. CONCLUSIONS: Since the use of PEEP in the American-European Consensus criteria for ARDS is not mandatory, that definition does not reflect the true severity of lung damage and outcome. Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted.

Adolescent↗

Newer ventilatory strategies.

Over the past year a large number of innovations in mechanical ventilation have been evaluated. Three of the most exciting are non-invasive positive pressure ventilation, tracheal gas insufflation and partial liquid ventilation. Non-invasive positive pressure ventilation is now clearly a standard of care in the management of an acute exacerbation of chronic obstructive pulmonary disease. In addition, its use in other clinical settings is being actively explored. Tracheal gas insufflation appears to be a useful adjunct to mechanical ventilation for the management of carbon dioxide but requires manufacturer-designed devices for safe application. The effects of partial liquid ventilation on lung injury have been more clearly defined in the past year as well as approaches to provide gas ventilation during partial liquid ventilation.

Journal Article↗

Ventilator-associated lung injury.

There is injury caused in numerous animal species when overdistending airway pressure and volume are delivered. The extent of this injury is attenuated by the application of PEEP. Patient case series point to the benefit of LPVS. In randomized controlled trials, the data may appear confusing. However, based on the data from the Amato and colleagues' trial, it seems prudent to employ an LPVS based on the individual patient's lung mechanics. Based on the trials discussed it appears that many have been convinced of the detrimental effects of high peak alveolar pressure. It remains to convince clinicians of the beneficial effects of the use of higher PEEP early in ARDS based on respiratory system mechanics of the individual patient and to use recruitment maneuvers. In conclusion, I concur with Dreyfuss and Saumon and Slutsky and Tremblay that the use of an LPVS may not only attenuate the severity of ARDS by preventing VALI, but may also prevent MODS or attenuate its severity.

Animals↗

Expiratory phase tracheal gas insufflation and pressure control in sheep with permissive hypercapnia.

Tracheal gas insufflation (TGI) has been shown to be a useful adjunct to mechanical ventilation, decreasing PaCO2 during permissive hypercapnia. While TGI can be used either with pressure (PCV) or volume-controlled ventilation and continuously or only during the expiratory phase (Ex-TGI), there are no controlled studies evaluating the effects of Ex-TGI with PCV in acute lung injury when the direction of the insufflated flow or the inspiratory:expiratory (I:E) ratio are varied. We evaluated the effect that Ex-TGI with PCV would have on CO2 removal during both direct and reverse insufflated flow direction with varied I:E ratios when peak airway pressure, total positive end-expiratory pressure (PEEP), and tidal volume (VT) were kept constant. In addition we examined the effect that insufflation flow directed toward the mouth (reverse flow) would have on the generation of PEEP compared with flow directed toward the carina (direct flow). After saline lavage, nine sheep were ventilated with PCV to a baseline PaCO2 of 80 mm Hg. Ex-TGI (10 L/min) was then randomly applied in the reverse and direct direction with I:E set at 1:2 or 2:1. During 1:2 I:E PaCO2 decreased from 78 +/- 4 mm Hg to 60 +/- 7 mm Hg (23.5 +/- 8.9%) with direct flow and to 64 +/- 5 mm Hg (18.5 +/- 5.5%) with reverse flow (p < 0.05), whereas during 2:1 I:E PaCO2 decreased from 80 +/- 4 mm Hg to 69 +/- 8 mm Hg (13.7 +/- 9.2%) with direct flow and to 66 +/- 4 mm Hg (17.2 +/- 4.4%) with reverse flow (p < 0.05). Greater PEEP was developed with direct flow (2.8 cm H2O I:E 1:2 and 4.0 cm H2O I:E 2:1) than with reverse flow (-0.9 cm H2O I:E 1:2 and -0.4 cm H2O I:E 2:1), p < 0.05. There was no difference in the PaCO2 change between I:E with reverse flow, but the PaCO2 decrease was greater (p < 0.05) during 1:2 versus 2:1 I:E with direct flow. CO2 removal during PCV and Ex-TGI is more consistent with reverse flow than with direct flow and PEEP level is less affected by TGI with reverse flow than with direct flow.

Animals↗

The effect of mode, inspiratory time, and positive end-expiratory pressure on partial liquid ventilation.

Partial liquid ventilation (PLV) has been shown to be an effective means of improving oxygenation in the injured lung. However, little is known about how approach to ventilation during PLV affects gas exchange and pulmonary mechanics. We hypothesized that gas exchange and pulmonary mechanics would be best with positive end-expiratory pressure (PEEP) set above the lower inflection point (LIP) of the pressure-volume (P-V) curve regardless of mode of ventilation or inspiratory to expiratory time (I:E) ratio and that the efficiency of ventilation would be greatest with volume-controlled ventilation (VCV) compared with pressure-controlled ventilation (PCV) and with long inspiratory time as compared with short inspiratory time. Lung injury was induced in 14 sheep by lavage, 10 of which were studied. Sheep were then assigned to high-PEEP (Group H, n = 5) and low-PEEP (Group L, n = 5) groups. In Group H applied PEEP was set at the LIP and in Group L applied PEEP was set at 5 cm H2O after the lung was filled with perflubron (PFB). We randomly compared VCV and PCV with I:E ratios of 1:2, 1:1, and 2:1. Peak inspiratory pressure and VT were adjusted to maintain a constant end-inspiratory plateau pressure (Pplat) of about 25 cm H2O in both groups and a constant total PEEP of about 5 cm H2O in Group L and about 12 cm H2O in Group H. There were no differences in oxygenation among modes in Group H. In Group L VCV 2:1 and all of the PCV modes in Group L had a lower PaO2 than VCV 1:1 (p < 0.05). PaCO2 and VD/VT were significantly different (p < 0.05) among modes. VD/VT was highest during PCV 1:2 with PEEP of 5 cm H2O (p < 0.05). Quasi-static compliance in Group H was higher than in Group L (p < 0.05). We conclude that during low PEEP gas exchange deteriorated in VCV with long inspiratory time and in PCV. Oxygenation was enhanced during VCV 1:1 when compared with VCV at longer I:E ratios or PCV at any I:E ratio. With PEEP set at the LIP, adequate gas exchange and improved lung mechanics could be obtained in all modes assessed.

Animals↗

Pressure-release tracheal gas insufflation reduces airway pressures in lung-injured sheep maintaining eucapnia.

Although tracheal gas insufflation (TGI) has proved to be a useful adjunct to mechanical ventilation, end-inspiratory as well as end-expiratory pressures may increase. We investigated the ability of continuous-flow TGI to maintain eucapnia while reducing airway pressure (Paw) and tidal volume (VT). Seven sheep (36 +/- 2 kg) were ventilated using the Dräger Evita 4 in the pressure control plus mode where flow is released via the expiratory valve to maintain constant inspiratory pressure. To avoid TGI-generated positive end-expiratory pressure (PEEP), a prototype reverse flow TGI tube was used. Two TGI flows (5 and 10 L/min) were investigated pre- and postsaline lavage-induced lung injury. Inspiratory pressures and VT were significantly reduced as TGI flow increased. At 10 L/min TGI flow the carinal pressures (Pcar) and VT were reduced pre- and postinjury by 15% and 20%, and by 28% and 34%, respectively. Tidal volume to dead space ratio (VD/VT) decreased preinjury from 0.49 +/- 0.1 to 0.18 +/- 0.2 and postinjury from 0.62 +/- 0.1 to 0.33 +/- 0.1 at a TGI flow of 10 L/min. The combination of the reverse flow TGI tube and a ventilator with an inspiratory pressure relief mechanism kept set end-inspiratory and end-expiratory pressures constant. This TGI system effectively reduced set Paw and VT while maintaining eucapnia.

Airway Resistance↗

The effect of heliox on nebulizer function using a beta-agonist bronchodilator.

OBJECTIVE: To evaluate nebulizer performance when heliox was used to power the nebulizer. METHODS: Conventional and continuous nebulizer designs were evaluated. The conventional nebulizer was used with 5 mg albuterol and flows of 8 L/min air, 8 L/min heliox, and 11 L/min heliox; it was also used with 10 mg albuterol and a heliox flow of 8 L/min. The continuous nebulizer was set to deliver 10 mg of albuterol over 40 min at flows of 2 L/min air, 2 L/min heliox, and 3 L/min heliox; it was also used with 20 mg albuterol and a heliox flow of 2 L/min. A cotton plug at the nebulizer mouthpiece was used to trap aerosol during simulated spontaneous breathing. The amount of albuterol deposited on the cotton plug was determined spectrophotometrically. Particle size was determined using an 11-stage cascade impactor. RESULTS: For both nebulizer designs, particle size and inhaled mass of albuterol decreased significantly (p < 0.001) when the nebulizer was powered with heliox rather than air. When powered with heliox, the reduction in inhaled mass of albuterol was less for the conventional nebulizer (16%) than the continuous nebulizer (67%). The nebulization time, however, was more than twofold greater with heliox (p < 0.001). Increasing the flow of heliox increased the particle size (p < 0.05), inhaled mass of albuterol (p < 0.05), and inhaled mass of particles 1 to 5 microm (p < 0.05) to levels similar to powering the nebulizer with air at the lower flow. Increasing the albuterol concentration in the nebulizer and using the lower heliox flow increased the inhaled mass of albuterol (p < 0.05) while maintaining the smaller particle size produced with that flow. CONCLUSIONS: The use of heliox to power a nebulizer affects both the inhaled mass of medication and the size of the aerosol particles. The flow to power the nebulizer should be increased when heliox is used.

Adrenergic beta-Agonists↗

Expiratory phase and volume-adjusted tracheal gas insufflation: a lung model study.

OBJECTIVE: To evaluate in a lung model the effects of expiratory-phase tracheal gas insufflation (expiratory-phase TGI) with both volume and pressure control ventilation, and tidal volume-adjusted continuous flow TGI (volume-adjusted TGI) on system pressures and volumes. DESIGN: Single-compartment lung model. SETTING: Research laboratory in a university medical center. INTERVENTIONS: Expiratory-phase TGI was established, using a solenoid valve activated by the ventilator. Volume-adjusted TGI was applied by reducing tidal volume (VT) by the product of TGI flow and inspiratory time. Ventilation was provided with pressure control of 20 cm H2O or volume control ventilation with VT similar to that with pressure control ventilation. A rate of 15 breaths/min and positive end-expiratory pressure (PEEP) of 10 cm H2O were used throughout. Inspiratory time periods of 1.0, 1.5, 2.0, and 2.5 secs were used with TGI flows of 0, 4, 8, and 12 L/min. Lung model compliance (mL/cm H2O) and resistance (cm H2O/L/sec) combinations of 20/20, 20/5, and 50/20 were used. MEASUREMENTS AND MAIN RESULTS: In expiratory-phase TGI with pressure control ventilation, peak alveolar pressure remained constant, PEEP increased (p < .01) and VT decreased (p < .01). In expiratory-phase TGI with volume control ventilation and volume-adjusted TGI, there were significant increases in peak alveolar pressure and PEEP (p < .01). Readjustment of VT in volume-adjusted TGI was impossible with longer inspiratory time (> or = 2 secs) and higher TGI flows (> or = 8 L/min). CONCLUSIONS: The marked increases in system pressures and volumes observed with continuous-flow TGI can be avoided with expiratory-phase TGI and volume-adjusted TGI.

Insufflation↗

Positive end-expiratory pressure improves gas exchange and pulmonary mechanics during partial liquid ventilation.

Partial liquid ventilation (PLV) with perflubron (PFB) has been proposed as an adjunct to the current therapies for the acute respiratory distress syndrome (ARDS). Because PFB has been also referred to as "liquid PEEP," distributing to the most gravity-dependent regions of the lung, less attention has been paid to the amount of applied positive end-expiratory pressure (PEEP). We hypothesized that higher PEEP levels than currently applied are needed to optimize gas exchange, and that the lower inflection point (LIP) of the pressure-volume curve could be used to estimate the amount of PEEP needed when the lung is filled with PFB. Lung injury was induced in 23 sheep by repeated lung lavage with warmed saline until the PaO2/FIO2 ratio fell below 150. Five sheep were used to investigate the change of the LIP when the lung was filled with PFB in increments of 5 ml/kg/body weight to a total of 30 ml/kg/body weight. To evaluate the impact of PEEP set at LIP +1 cm H2O we randomized an additional 15 sheep to three groups with different doses (7.5 ml, 15 ml, 30 ml/kg/body weight) of PFB. In random order a PEEP of 5 cm H2O or PEEP at LIP +1 cm H2O was applied. The LIP decreased with incremental filling of PFB to a minimum at 10 ml (p < 0.05). Increasing PEEP from below LIP to LIP +1 cm H2O at 15 and 30 ml/kg resulted in an improvement in PaO2 from 152 +/- 36 to 203 +/- 68 (NS) and 193 +/- 57 to 298 +/- 80 (p < 0.05), respectively. Pulmonary shunt, and ratio of dead space volume to tidal volume (VD/VT) decreased, and static lung compliance increased with PEEP at LIP +1 cm H2O (p < 0.05). No changes were observed in hemodynamics. We conclude that increasing the dose of PFB shifts the LIP to the left, and that setting PEEP at LIP +1 cm H2O improves gas exchange at moderate to high doses of PFB.

Analysis of Variance↗

Ventilatory and cardiovascular responses to inspired He-O2 during exercise in chronic obstructive pulmonary disease.

Blunted maximum cardiac output and systemic O2 extraction could constitute primary limits to exercise in severe chronic obstructive pulmonary disease (COPD) or they could simply reflect cessation of exercise because of abnormal pulmonary mechanics. To determine which is the case, eight consecutive patients with severe COPD (FEV1 = 0. 56 +/- 0.04 L, mean +/- SEM), five of whom had alpha1-antiprotease deficiency, performed two incremental cycling tests while breathing N2-O2 or He-O2. Expired gases and V E were measured, and radial and pulmonary arterial blood was simultaneously sampled each minute. Peak exercise V E was higher with He-O2 than with N2-O2 (25.5 +/- 2. 2 versus 19.3 +/- 1.5 L/min, p = 0.002) and PaCO2 was lower (42 +/- 2 versus 46 +/- 2 mm Hg, p = 0.0003). V O2max improved only modestly (594 +/- 75 versus 514 +/- 54 ml/min, p = 0.04), and was accompanied by an increase in peak exercise CaO2 (18.7 +/- 0.9 versus 17.6 +/- 0. 9 ml/dl, p = 0.02). Peak Fick cardiac output was decreased (39 +/- 3% pred) and CvO2 was elevated (130 +/- 10% pred), and neither improved with He-O2 (p > 0.05 for each). Abnormal peak exercise cardiac output and systemic O2 extraction in severe COPD cannot be fully accounted for by limiting pulmonary mechanics and may contribute to exercise intolerance.

Administration, Inhalation↗

Delivery of inhaled nitric oxide using the Ohmeda INOvent Delivery System.

OBJECTIVES: We evaluated the Ohmeda INOvent Nitric Oxide Delivery System, which uses an inspiratory flow sensor to inject a synchronized and proportional nitric oxide (NO) flow into the mechanical ventilator circuit. This system should deliver a constant NO concentration independent of ventilator mode, minute ventilation, fraction of inspired oxygen, or ventilator brand. It should also minimize nitrogen dioxide (NO2) formation. METHODS: NO delivery by the INOvent and a premixing NO delivery system were compared using two ventilators (Puritan-Bennett 7200 and Servo 900C). NO concentration was measured within the trachea of an attached lung model using a fast-response chemiluminescence NO analyzer. NO concentration was also measured in the inspiratory limb using the electrochemical analyzer of the INOvent. For three NO concentrations (2, 5, and 20 ppm), the ventilators were set for constant flow volume control ventilation, pressure control ventilation, and spontaneous breathing with pressure support ventilation or synchronized intermittent mandatory ventilation. Different tidal volumes (300, 500, 750, and 1,000 mL) and inspiratory times (1 and 2 s) were evaluated. NO2 formation for both ventilators and delivery systems were evaluated at 20 ppm and 95% O2-. RESULTS: Regardless of ventilatory pattern, both systems delivered a constant NO concentration. The error between the target and the delivered NO dose for the INOvent was -1.3+/-3.6% with the Puritan-Bennett 7200 and -3.9+/-4.3% with the Servo 900C. For the premixing system, the error was -5.5+/-4.8% with the Puritan-Bennett 7200 and -6.7+/-6.2% with the Servo 900C. NO2 concentrations were 0.5+/-0.1 ppm during NO delivery by the INOvent, 5.8+/-1.6 ppm when NO was premixed with air, 0.3+/-0.1 ppm when NO was premixed with N2. CONCLUSION: The INOvent provides a constant NO concentration independent of the ventilatory pattern, and NO2 formation is minimal.

Administration, Inhalation↗

Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo.

The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS). Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; P < 0.001). The increase in SS RBC oxygen affinity correlated with the NO concentration. The P50 of AA RBCs was unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing was discontinued, the RBC P50 remained decreased in five of seven volunteers in whom the ODC was measured. There was no RBC P50 change (P > 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD.

Adolescent↗

Nitric oxide (NO) measurement accuracy.

BACKGROUND: Evaluation of the clinical utility of NO requires accurate assessment of inspired [NO]. Currently, chemiluminescence analyzers are the clinical standard for analysis; however, their performance in the clinical setting has not been systemically evaluated. METHODS: We evaluated the performance of four chemiluminescence analyzers (270B NOA, Sievers Instruments, Inc.; CLA 510S, Horiba Co., Ltd.; CLD 700 AL, Eco Physics Corp.; Model 42, Thermo Environmental Instruments Inc.) in simulated clinical settings. Transport delay and dynamic 95% response time were measured by the balloon in a glass chamber puncture technique. Fluctuating [NO] in a continuous flow of gas and [NO] during mechanical ventilation, where NO was premixed prior to entering the ventilator, were evaluated. RESULTS: Transport delay ranged from 1.02 +/- 0.02 to 24.36 +/- 2.47 s (p < 0.05) and the 95% response time ranged from 0.22 +/- 0.04 to 70.03 +/- 0.03 s (p < 0.05). Accurate analysis of [NO] in a continuous flow system was only possible with the most rapid response analyzer (270B NOA). All other analyzers under reported the maximum [NO] (p < 0.05) and over reported the minimum [NO] (p < 0.05). All analyzers accurately determined [NO] in the inspiratory limb of the ventilator circuit, but none accurately determined [NO] at the airway opening. CONCLUSIONS: Measurements of inhaled [NO] can vary greatly, dependent upon the performance characteristics of the analyzer and the location of NO analysis. All studies evaluating the clinical use of NO should fully describe the technical gas delivery methodology and the response time and transport delay of the chemiluminescence analyzer used.

Administration, Inhalation↗

Evaluation of electrochemical nitric oxide and nitrogen dioxide analyzers suitable for use during mechanical ventilation.

OBJECTIVE: Inhaled nitric oxide (NO) is increasingly being used in the treatment of diseases characterized by hypoxemia and pulmonary hypertension. To avoid complications, accurate quantitative analysis of NO and NO2 is necessary during this therapy. We evaluated the accuracy of electrochemical NO and nitrogen dioxide (NO2) analyzers suitable for use during mechanical ventilation. METHODS: We evaluated six electrochemical NO analyzer brands (Bedfont, B & W, Dräger, EIT, Pulmonox, Saan). All were calibrated and used per manufacturer's specifications. An adult mechanical ventilator was used to produce serial dilutions of NO with O2 for [NO] of 0-80 ppm. F1O2 settings of 0.90, 0.70, 0.50, 0.30, and 0.21 were used. Settings of low, moderate, and high ventilation pressures were evaluated. Gas was sampled from the inspiratory limb of the ventilator circuit using either a sidestream or mainstream technique. [NO] was also measured using a calibrated chemiluminescence analyzer. For the analyzers that measured NO2, serial dilutions of 8.5 ppm NO2 with O2 were analyzed using chemiluminescence and the electrochemical analyzers. RESULTS: Bias +/- precision for [NO] by individual devices ranged from 1.8 +/- 1.9 ppm to -1.0 +/- 0.7 ppm. There were significant differences in the bias between analyzers (P < 0.001), pressure settings (P < 0.001), and NO level (P < 0.017). The difference in bias between levels of F1O2 was not significant (P = 0.062). Bias +/- precision for NO2 ranged from 0.18 +/- 0.12 ppm to -0.14 +/- 0.13 ppm, with a significant difference between analyzers (P < 0.001). CONCLUSIONS: The bias and precision of these analyzers was acceptable for clinical use. The devices tended to be most accurate at [NO] < or = 20 ppm-the clinical conditions at which NO is most commonly used.

Administration, Inhalation↗