In recent years, there has been renewed interest in the use of helium as a temporizing agent to reduce work of breathing and allow time for the more standard forms of therapy to reach peak effect.
By James B. Fink, MS, RRT
Helium is a rare, chemically and physiologically inert gas that is more viscous and less dense than oxygen or air. These properties have been invoked clinically since 1934 to reduce airway resistance and work of breathing in patients with airway obstruction.[1-2] Helium was successfully used during the 1930s, when the alternatives for treatment of bronchospasm were limited. During World War II, the poor availability of helium and the advent of more effective bronchodilators allowed the use of helium to pass into relative clinical obscurity.
In recent years, there has been renewed interest in the use of helium as a temporizing agent to reduce work of breathing and allow time for the more standard forms of therapy to reach peak effect.
The clinical benefits ascribed to helium-oxygen mixtures include:
- improved ventilation and reduced barotrauma;
- reduced peak airway and plateau pressures;
- increased tidal volumes;
- reduced inspiratory-expiratory ratios;
- improved homogeneity of gas distribution;
- improved elimination of carbon dioxide; and
- movement of the equal-pressure point of the airways upstream.
Helium-oxygen use can reduce work of breathing in severe airway obstruction in patients with asthma and fixed airway obstruction.
The driving pressure required to produce turbulent flow varies directly with resistance and the square of flow; more pressure is required to maintain turbulent flow than to maintain laminar flow. Turbulent flow is density dependent, while laminar flow is density independent. In the tracheobronchial tree, a laminar flow normally exists in airways that are less than 2 mm in diameter. Turbulent flow has been observed in the upper respiratory tract, the glottis, and the central airways (down to the 10th generation, in healthy subjects). This is the portion of the airway that is considered to be density dependent.
Because a mixture of 80% helium and 20% oxygen is of lower density and higher viscosity than air, the Reynolds number for the mixture will be about one third of the Reynolds number for air at the same flows and airway dimensions.
The use of low-density gas mixtures may be of benefit to patients with various forms of obstructive airway disease, including acute upper-airway obstructions (such as luminal compression or viral croup), acute asthma, and the acute exacerbations of chronic obstructive pulmonary disease (COPD). A reduction in gas density may significantly reduce the work necessary for ventilation and may also reduce gas trapping.
The use of helium-oxygen mixtures in patients with status asthmaticus may not only reduce work of breathing, but may also improve alveolar ventilation and improve removal of carbon dioxide from the lung. Helium has been shown to improve alveolar ventilation within the lung. Improved distribution of ventilation may be of benefit, given the increased proportion of poorly ventilated/poorly perfused units associated with bronchospasm. Helium enhances the diffusion effect on the elimination of carbon dioxide, which diffuses more than four times more rapidly through helium mixtures than through nitrogen-oxygen mixtures. It stands to reason that a greater volume of carbon dioxide would be eliminated, for the same pulmonary capillary pressure, per unit of time.
Yahagi et al measured the effect of a helium-oxygen mixture on respiratory index, shunting, and dynamic compliance in 12 patients who had impairment of oxygenation following cardiac surgery. Oxygenation improved, shunting decreased, and dynamic compliance increased, suggesting that helium-oxygen use improved oxygenation by recruiting previously obstructed small airways and alveoli.
Houck et al modeled obstructed airways with a series of four endotracheal tubes narrowed with C-clamps (monitoring resistance with constant flows and having volunteers simulate tidal flow). They used helium-oxygen ratios of 80:20, 60:40, and 40:60, as well as oxygen alone. The effect of a helium-oxygen mixture in reducing resistance and pressure in obstructed airways was linear (P<.016) and inversely proportional to helium concentration. Reductions were larger with increased obstruction (P<.07). Resistance dropped 42% and airway pressure dropped 58% upon administration of a helium-oxygen mixture. Papmoschou demonstrated that a helium-oxygen mixture does not need to be laminar to provide higher flow rates, and that its benefits persist under turbulent conditions. The pressure-flow relationships show that, for a given pressure difference across the lungs, the oxygen flow rate increases considerably when a nitrogen-oxygen mixture is replaced by a helium-oxygen mixture. This improvement is on the order of 50% and 30% at oxygen concentration of 20% and 40%, respectively. A similar result is found for flow through an airway restriction (with the restriction modeled as a circular tube). At a given flow rate, the pressure difference across a restriction drops sharply as the nitrogen-oxygen mixture is replaced by a helium-oxygen mixture; this is a result corroborated by experimental and clinical evidence. The advantage of helium-oxygen use persists under fully turbulent conditions.
Skrinskas et al described the use of oxygen and a helium-oxygen ratio of 80:20 with an in vitro model that had a fixed orifice 4.76 mm in diameter connected to a spirometer with a pressure transducer.The model was tested with constant flow. The same device was tested in vivo. Work of breathing was determined in one subject by using a plethysmograph and an esophageal balloon. Static pressure-volume curves were observed while the subject breathed through a Venturi tube at 24 to 36 breaths per minute with a target volume of 1 L. Work of breathing doubled with increasing respiratory rate for both gas mixtures, but was decreased by 36% (rate 24) and 31% (rate 36) compared with air, when the subject breathed a helium-oxygen mixture.
While textbook dogma suggests that helium-oxygen ratios need to be greater than 60:40 to gain mechanical advantage, Lu et al found that 40:60 was an optimal mixture for maintaining desirable arterial blood gas (ABG) values in dogs with acute airway obstruction.
While the initial effect of helium-oxygen use begins with its administration, 20 minutes may be required to demonstrate its full effect. Several studies have shown variable effects over time. Curtis et al treated an inoperable obstruction of the upper airway due to extrinsic malignancy with 80:20 helium-oxygen for 48 hours using a non-rebreathing mask; meanwhile, the tumor was treated to reduce its size. The authors documented improving ABG levels over the first several hours of administration.
In contrast, when pediatric inpatients with asthma were given a 70:30 helium-oxygen or air for 15 minutes in a randomized, double-blind crossover study, there was no difference in either clinical or dyspnea scores. Verbeek and Chopra studied 12 patients with acute asthma who had forced expiratory volume in 1 second (FEV1) values that were 20% to 60% of those predicted. Measurement of FEV1 after five minutes of 70:30 helium-oxygen revealed no significant differences.
Kudukis et al looked at the effects of 80:20 helium-oxygen or room air on dyspnea and pulsus paradoxus in 18 children (aged 16 months to 16 years) with status asthmaticus. A helium-oxygen mixture was administered at 10 LPM using a non-rebreathing mask. Values measured every 15 minutes during and after intervention revealed that a helium-oxygen mixture significantly lowered pulsus paradoxus, increased peak flow, lessened the dyspnea index, and spared three patients from planned intubations. Hollman et al,15 treating children with acute bronchiolitis, found significant improvements after 20 minutes of therapy.
The use of helium-oxygen mixtures is adjunctive. If therapy is interrupted and the patient returns to breathing an oxygen-air mixture, the mechanical low-density benefit is lost immediately. Therapy that is directed at the primary problem should always accompany the use of a helium-oxygen mixture.
A helium-oxygen mixture also has a role in treating pediatric patients with postextubation stridor. Previous work had demonstrated that airway obstruction with stridor was present in 92% of patients requiring intubation. Eight pediatric patients with postextubation stridor who were unresponsive to racemic epinephrine were treated with 70:30 or 50:50 helium-oxygen for 28+/-5 hours, with distress scores decreasing from 6.8 to 2. Only two of the eight required reintubation, and both had experienced stridor for a longer time than the others before the initiation of helium-oxygen therapy.
Ten patients with status asthmaticus and respiratory acidosis were treated with a helium-oxygen mixture in addition to bronchodilators and corticosteroids. Significant reversal of acidosis was noted within the first 20 minutes, and not one patient required subsequent intubation.
Kass and Castriotta studied 12 consecutive asthma patients, over a 2-year period, who presented to the emergency department with acute respiratory acidosis. They were treated with 60:40 or 70:30 helium-oxygen (five via ventilator and seven via face mask). The subjects’ PaCO2 levels dropped from 57.9 to 47.5 mm Hg 49 minutes after the initiation of therapy. Eight responders (67%), defined as having PaCO2 levels that were normal or that improved 15% or more and as having an increase in pH of 0.05 or more, had experienced a shorter duration of symptoms (less than 24 hours) and lower pH levels prior to treatment. All patients were sufficiently improved after 24 hours to have helium-oxygen use discontinued without undergoing clinical deterioration.
Manthous et al reported on emergency department patients who, after 30 minutes of b-agonist therapy, had pulsus paradoxus of more than 15 mm Hg and peak expiratory flow (PEF) of less than 250 L/min. Breathing a helium-oxygen mixture for 15 minutes reduced pulsus paradoxus by 50%, most probably because of reduction in airway resistance. These results are compatible with the density dependence of the increased resistance seen in narrowed bronchi between the carina and the 10th airway generation, which accounts for about 70% to 85% of lower pulmonary resistance in the normal human lung.
In this study, pulsus paradoxus returned to normal after helium-oxygen use was discontinued. PEF increased 35%, suggesting that expiratory airway resistance is about as density dependent as inspiratory airway resistance (38%). Helium-oxygen use decreased inspiratory and expiratory resistance and dyspnea in patients presenting to the emergency department with an exacerbation of asthma. These effects may provide a window of time of reduced respiratory distress, during early treatment of a severe exacerbation of asthma, before definitive bronchodilators or anti-inflammatory medications become effective.
Helium-oxygen use is suggested for patients with very severe exacerbations of asthma in whom intubation appears imminent and for patients who do not respond to vigorous bronchodilator therapy.
The effect of 80:20 helium-oxygen was evaluated in 15 patients with severe COPD by Swidwa et al. Forced residual capacity fell during helium-oxygen; there were nonsignificant changes in minute ventilation, tidal volume, frequency, or inspiratory-expiratory ratio. Of the 15 patients, 11 had reduced PaCO2 levels and carbon dioxide excretion during rest while breathing a helium-oxygen mixture. Expiratory flows were increased for a given lung volume, as expected. The authors speculate that use of a less dense gas in obstructed patients can result in less hyperinflation (with changes in chest-wall and diaphragm configuration), placing the inspiratory muscles at better mechanical advantage, improving muscle efficiency, and reducing work of breathing. Helium-oxygen use should be considered as a noninvasive means of support for patients with severe COPD when an acute reduction in PaCO2 and work of breathing is likely to be beneficial.
The effects of helium on COPD patients were further clarified by Oelberg et al, who had eight patients perform two incremental cycling tests while breathing air and a helium-oxygen mixture. Peak minute exhaled volumes during exercise were higher with helium-oxygen (25.5 LPM versus 19.3 LPM) and PaCO2 was lower (42 mm Hg versus 46 mm Hg, P=.0003). The improved mechanics, however, did not fully account for exercise intolerance in COPD.
There have also been a few reports of mechanical ventilation with helium. Gluck et al reported on seven patients with status asthmaticus who were intubated for respiratory failure with elevated airway pressures and persistent respiratory acidosis. They were successfully ventilated with 60:40 helium-oxygen, with rapid reduction in airway pressures and carbon dioxide retention, and resolution of acidosis, and there were no untoward effects. The authors hypothesized that beneficial effects were due to high kinematic viscosity, the high binary diffusion coefficient for carbon dioxide, and the high diffusivity of helium. Their findings suggest that helium-oxygen mixtures should be considered for use in asthma patients with respiratory acidosis who fail conventional therapy. Sauder et al22 reported similar positive results using helium-oxygen and conventional mechanical ventilation in the treatment of large-airway obstruction and respiratory failure in an infant.
Pizov et al reported on seven sedated and paralyzed patients in respiratory failure with PaCO2 levels of more than 50 mm Hg and peak inspiratory pressures of more than 35 cm H2O. They were ventilated in volume-control mode at tidal volumes of 5 to 7 mL/kg, with tracheal gas insufflation administered at 2, 4, and 6 LPM with oxygen and 100% helium. Tracheal gas insufflation with both gases decreased PaCO2 (P<.05) and increased airway pressure at all flows. At flow rates of 6 LPM, however, tracheal gas insufflation with helium resulted in lower peak inspiratory pressures than those seen for oxygen. The authors concluded that tracheal gas insufflation with helium was more effective than oxygen insufflation at all flow rates (P<.05).
Practical Aspects for Administration
The use of helium-oxygen in a clinical practice requires careful attention to several key issues. The following considerations are provided to demonstrate only a few of the available methods to safely administer He:O2. In the absence of helium-specific flowmeters, oxygen or air flowmeters may be used with the conversion factors used in Table 1, page 76. The conversion factor can be found by dividing the square root of the density of the gas for which the flowmeter is calibrated, by the square root of the density of the He:O2 mixture. Desired flow to the patient divided by the conversion factor yields the flow to be dialed in on the meter. Actual flow is found by multiplying the correction factor by the flow rate indicated on the meter.
Key Issues for Administration
Helium-oxygen is commercially provided in mixtures of 80:20 and 70:30. In patients who do not require more than 30% oxygen, helium-oxygen may be administered directly from the cylinder via regulator and flowmeter to a tightly fitting non-rebreathing oxygen mask (with all one-way valves in place). Using an oxygen flowmeter, flow rates of 5 to 10 LPM (delivering 9 to 18 LPM) should be sufficient to provide high-flow therapy. When additional oxygen is required to maintain an oxygen saturation level of 90%, low-flow oxygen may be administered via nasal cannula.
Closed-dilution (gas-injection) nebulizers are well suited for helium-oxygen dilution with oxygen. The oxygen source should be attached to the nebulizer input and the helium-oxygen source should be attached to the secondary inlet port. A standard oxygen analyzer can be used to determine helium concentration indirectly (that is, what is not oxygen must be helium).
If oxygen blenders are required, a low-flow blender with minimal leakage should be selected, attaching the helium-oxygen source to the air inlet.
Most modern ventilators mix and deliver gas based on the internal measurement of gas pressure and on predicted flow rates through fixed orifices and valves, assuming that the density of the gas being delivered is in the range of air or oxygen–creating large errors in volume and flow delivery (and monitoring). Some common adult ventilators will not deliver helium-oxygen mixtures at all, while others may be used with a variety of compensatory adjustments of both breath and alarm parameters. Constant flow, time-limited, or pressure-limited ventilators (such as those popular for use with infants) and piston-based volume-limited ventilators (now seen more commonly in the subacute arena) are the most reliable devices for helium-oxygen delivery.
It is best to explore how a specific ventilator will perform with helium-oxygen using a volume-displacement test lung before committing the ventilator to use for a critically ill patient during an emergency situation. Clinical sites should perform extensive bench testing and should develop written administration procedures prior to initiating this therapy for ventilated patients.
Although pressure readings remain accurate, use of pneumotachometers to monitor flow and calculate volumes can yield unreliable, and sometimes erratic, results. The readings of these devices are affected by the differences in gas density, viscosity, and pressure seen for helium-oxygen mixtures. At least one monitor available for bedside use in the intensive care unit has built-in algorithms for varying concentrations of helium, nitrogen, and oxygen, and appears to be fairly accurate at flow rates of helium-oxygen that are higher than 2 to 3 LPM. Another option for monitoring at the bedside is the use of a bellows or volume-displacement spirometer.
Monitoring focused on the patient’s condition and response should include pulse oximetry with supporting ABG sampling and assessments of heart rate, pulsus paradoxus, arrhythmia, shortness of breath, apparent work of breathing, and dyspnea levels.
For mechanical ventilation with a helium-oxygen mixture, start with the maximum concentration of helium that permits an oxygen saturation level of more than 90%. Successful ventilation with helium-oxygen would be evidenced by decreases in PaCO2, peak and plateau airway pressures, and intrinsic positive end-expiratory pressure.
Patients with severe asthma, who require mechanical ventilation for a relatively short period of time, may be good candidates for noninvasive mechanical ventilation. Standard devices delivering bilevel ventilation may not be able to deliver sufficient flows of a helium-oxygen mixture to maintain an adequate helium concentration. Use of a standard ventilator that has been proven to work effectively with helium-oxygen, with a properly fitted mask, may prove to be a more viable alternative for this patient population.
Many of the patients who might benefit from the administration of helium to reduce work of breathing would also benefit from improved delivery of aerosolized bronchodilators to the lung. A helium-oxygen mixture can improve the delivery of aerosols. Anderson et al reported on 10 subjects with asthma who inhaled 3.6 mm particles, with and without a helium-oxygen mixture, at 0.5 and 1.2 L/second. Lung retention was measured immediately and after 24 hours, with the latter value attributed to alveolar deposition. The increase in alveolar retention was larger in asthma patients than in previously studied healthy subjects. At both inspiratory flow rates, oral deposition was less and alveolar deposition was greater with the helium-oxygen mixture than with air.
Svartengren et al demonstrated that aerosol delivered to mechanically ventilated rabbits had a greater peripheral deposition with helium-oxygen than with air. There was a negative correlation between intra-tracheal peak pressures and peripheral deposition.
In the most comprehensive study to date, Hess et al evaluated nebulizer performance when a helium-oxygen mixture was used to power the nebulizer. The particle size and inhaled mass of albuterol decreased significantly (P<.001), increasing nebulization time more than twofold, when nebulizers were powered by helium-oxygen rather than air. The authors found that increasing the flow of helium-oxygen increased nebulizer output and particle size compared to those achieved with normal flow rates of air. The flow used to power the nebulizer should, therefore, be increased when a helium-oxygen mixture is used.
Cost of a Helium-Oxygen Mixture
The cost of helium-oxygen therapy may be high, as helium is more than 13 times as expensive as oxygen. Depending on flow rates, four to six tanks may be required for 24 hours of treatment at a cost of $320 to $480. There is little available outcomes information available to demonstrate whether this is money well spent.
If helium-oxygen treatment can reduce the work of breathing and respiratory failure can be avoided for a patient in the emergency department, the expense seems warranted and the investment seems sound. For the ventilated patient, reduced plateau pressures and lowered risks of pressure trauma and pneumothorax are attractive goals, but the relative financial merits of therapy are less clear.
Helium-oxygen use is clearly not for every patient with obstructed airways. Manthous et al suggest that helium-oxygen mixtures should be reserved for those patients with moderately severe obstructions that may be amenable to medical therapies; helium-oxygen may, in these cases, serve as a bridge therapy to reduce airway resistance and workload, tipping the scales in favor of the respiratory muscles until other therapies take hold. Such situations include post-extubation stridor and airway edema or infection, as well as severe exacerbation of asthma in patients who are slow to respond to standard therapies and who still have enough respiratory muscle reserve. In ventilated patients, helium-oxygen mixtures should similarly be reserved for those asthma patients with extreme hyperinflation in whom low airway pressures can not be achieved, with or without permissive hypercapnia.
James B. Fink, MS, RRT, is a program analyst, respiratory care, Edward Hines Jr Veterans Administration Hospital, Hines, Ill.
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