Helium-Oxygen Mixtures in Intubated Patients with Status Asthmaticus and Respiratory Acidosis

Helium-Oxygen Mixtures in Intubated Patients with Status Asthmaticus and Respiratory Acidosis· Eric H. Gluck, i\'.D., F.C.C.R;t Douglas J Onorato, M.D.;:f:. and Richard Castriotta, L\J.D., F.C.C.R§

Seven patients with status asthmaticus intubated for respiratory failure who had elevated airway pressures and persistent respiratory acidosis were successfully ventilated using a mixture of 60 percent helium and 40 percent oxygen. All patients experienced a rapid reduction in airway pressures, CO2 retention, and resolution of acidosis while breathing a helium-oxygen mixture. There were no untoward effects. Helium-oxygen mixtures improve ventilation by reducing the Reynolds number and reducing density

dependent resistance. Helium's beneficial effects are due to its high kinematic viscosity, high binary diffusion coefficient for COu and high diffusivity. Helium-oxygen mixtures should be considered for use in mechanically ventilated asthmatics with respiratory acidosis who fail conventional therapy. (Chest 1990; 98:693-98)

Status asthmaticus is a familiar clinical management problem confronting emergency, pulmonary and critical care physicians. It represents the penultimate event in a conlplex cascade of pathologic processes including diffuse airway inflammation, bronchoconstriction, and ahnorlnal ventilation/perfusion relationships.1 In general, deaths due to asthma are uncommon, yet there appears to be a multifactorial mediated rise in asthma mortality over the last ten years. 2 Classic teachings su~est that normocapnia and hypercapnia portend uimpending respiratory failure" which requires endotracheal intubation and mechanical ventilation. 3 However, this position has recently been challenged. 4 In fact, endotracheal intubation may intensify the degree of bronchospasm. 5 Moreover, generated airway pressures may exceed pressure limits causing ventilators to prematurely recycle, resulting in decreased alveolar ventilation. Despite disabling the alarms, there are instances ofsevere bronchospasm in which the ventilator is incapable of delivering sufficient tidal volume to reverse hypoventilation. In the past, halothane anesthesia has heen employed to ameliorate bronchospasm, hypoxia, and hypercapnia. Halothane therapy is logistically difficult to obtain and carries inherent risks. 6 Helium is an inert gas which has a long history of safe utilization in pulmonary medicine. Helium, because of its unique position on

the periodic table, is ideally suited to ventilation in asthmatic patients. We report seven intubated patients in whom severe status asthmaticus and respiratory acidosis \\'as not amenable to a~ressive conventional therapy but responded immediately to the inhalation of heliox.

*From the Hartford Hospital and Mount Sinai Hospital, Hartford, CT. tDireetor of t\1edical Intensive Care. tResearch Pulmonary Fello\\~ §Direetor of Pulmonary Medicine. Manuscript reeeived January 2; revision aecepted February 26. Reprint rel/ru~sts: Dr. Gluck, B5 Seymour Street, Hartford, CT06106

=

EPP equal pressure print; Heliox and 40% oxygen

=mixture of 60%

helium

MATERIALS AND METH()OS

Between June 1, 1987, and Dee 31, 1988, all patients 15 to 40 years old \\rjth a prior history of asthnla presentin~ to the emer~ency departments of Hartford Hospital or Mount Sinai Hospital, lIartfilrd, CT, \\lere <.'onsidered eligible for a trial of heliurn-oxyJten therapy. Patients were initially evaluated by emer~ency department physk-ians in <.'onjunetion with medieal housestafT and intubated on dinical Jtrounds after arterial blood Jtas measurements were obtained. All patients were immediately treated \\'ith 125 m~ methylprednisolone, 0.5 to 1.0 m~ aerosolized alhuten)l, 300 m~ aminophylline holus followed hy a 0.6 InWk~ (.'ontinuous infusion and 0.3 ml suheutaneous epinephrine. Ventilator parameters were adjusted to minimize peak aim'ay pressures. Aftt.-r review of the pertinent history, dia~nostic and ventilator parameters, patients were entered into the helium treatment protoeol if they exhibited a pI 1<7 .20, PaO z>60, PaC0 2 >50; a persistently elevated peak aim'ay pressure in exeess of 75 cm H 20 after 1 hour of conventional therapy; and a persistent hypercapnia and addosis after 1 hour of conventional therapy. Excluded from the protocol \\'ere patients who exhihited a 20 pereent fall in PaCD:! on subsequent arterial blood ~as measuretnents, or a reduction in peak aim'ay pressures to less than 75 em H 2 0 on (.'onventional therapy; a combined respiratory addosis and metabolic alkalosis Oil initial blood ~as measurements; historic.' or physieal eviden<.'C of cardiac, renal, Ilt-l1rolo~ie, ~astrointestinal or restrictive 11In~ dise&lse; and rClentgeno~raphie evidenee of infection or diffuse lun~ injury. Patients were admitted to the medical intensive care unit, Inonitored by ECG and pulse oximeter, and continued reeeivin~ intravenous aminophylline, (.'ortk-osteroids, and aerosolized f3-a~()nists. All patients "'ere paralyzed and sedated. All patients were initially mana~ed on a Puritan Bennett 7200. All patients were s\\'itched to a Bear 1 ventilator prior to the substitution of helium for nitro~en heeause the tidal volume is not re~ulated by in-line Row tneters. CHEST I 98 I 3 I SEPTEMBER. 1990

693

Table I-Arterial Blood Gases and Ventilation Parameters a/Intubated Status Asthmaticu8 Patients Breathing a 60%-40% Helium-Oxygen Mixture lIeliurn-Oxy~en

Nitro~en-Oxy~en*

Patient No.

A~e

Sex

16 21 34 39 28 23 30

F F M

1 2 3 4

5 6 7 *PI~

M ~t

M M

I:E Ratio

PIP

pH

Pcoz

P02

1:1.8 1:1.1 1:1.5 1: 1.2 1: 1.2 1:1.2 1:1.4

100 95 85 80 75 90 75

6.95 7.01 7.10 6.87 7.15 7.08 7.00

110 82 75 103 62 90 84

120 102 90 75

90

88 96

I:E Ratio 1:4 1:5 1:4.5 1:1.3 1:1.4 1:1.5 1:1.3

PIP

pH

Peo z

55 65 50 70 45

7.34 7.29 7.40 7.21 7.34 7.36 7.34

65 55 40 70

40 45

40

51

35

POz 95

98

98 88 92 90 100

peak inspiratory pressure in em H 20; Peo:!. partial pressure of CO 2 in mm H~; Po 2 , partial pressure of O 2 in mm H~.

Arterial blood ~as Ineasurernents were ohtained at ten-minute intervals until rn'o ('onsecutive values for PaCO z measured less than 42 mrn H~. Ventilator settin~s \\'ere periodically adjusted to maximize flow and minimize peak airway pressure. Pure helium at 50 psi, and PUrt~ oxy~en at 50 psi were delivered to the air port and oxy~en port. respectively. Adjustments were made \\ith the internal hlender to providt~ heliox mixtures from 80 to 60 per(.'ent helium. {;as from the patient side of the inspiratory limb was analyzed for oxygen percenhl~t~. An in-line Wri~ht spironleter, recalihrated for the density of helium. \\'as utilized to nleasure the tidal volumes and the inspiratory/expiratory ratios. A t\\'o-way analysis of variance was perforrned to test for the si~nificance of differences in the measured variables. RESULTS

All seven patients experienced a statistically significant (p
after the introduction of helium as the carrier gas (Table 1). The mean elapsed time for the reduction in Pco2 was 22.2 minutes. The mean reduction in Pco2 was 35.7 mm H~. There were no statistically significant changes in P0 2 (Fig 1). Six out of the seven patients had a precipitous fall in peak airway pressure after the onset of heliox breathing. The mean duration oftime until peak airway pressure nadir was 2.5 minutes. The mean reduction in airway pressure was 32.86 cm H 20. Patient 6 had a 2-hour trial of halothane anesthesia prior to the introduction of a 60 percent helium-40 percent oxygen mixture. After 5 minutes ofheliox treatment, both the peak airway pressure and the PC()2 were rapidly reduced.

7.5 7.4

• • • • • •

7.3

7.2

pH

7.1

~

7.0

Patient 1 Patient 2 Patient 3 Patient 4 Patient S Patient 6 Patient 7

6.9

6.8

Nitrogen-Oxygen

Helium-Oxygen

130

120 110 100 90

mmHg

80

70 60 50 40 30 20

694

Nitrogen-Oxygen

Helium-Oxygen

FIGURE 1. The response of Po2 , Pco:h and pH after chan~in~ from nitro~enoxy~en to helium-oxy~en mixtures.

Gas Mixtures in Intubated Patients (Gluck, Onorato, Castriotta)

All patients were extubated within 24 hours of intubation without complications. The mean duration ofheliox treatment was 6.3 hours (SEM ±2.3 hours). DISCUSSI()N

Ramsey first isolated helium from the mineral cleavite in 1895. Forty years later, Barach7 - 10 introduced mixtures of helium and oxygen to the medical community advocating its use for obstructive lesions of the larynx, trachea and airways. Helium enjoyed therapeutic use until 1940 when international hostilities, pharmacologic bronchodilators and mucolytic agents relegated helium to use as a investigational agent. In addition, autopsy reports suggesting mucus plugging as a prominent feature in deaths due to status asthmaticus further distanced helium from therapeutic use. II During the three decades after World War II, reports of helium applications have punctuated the clinical literature .12-15 Yet, helium has rarely been used for the treatment of asthma. 16.17 The physical properties of helium make it uniquely suited for use as a temporizing agent in patients with severe reactive airways disease, whether or not it is accompanied by mucus plugging. Helium is a biologically inert gas of low molecular weight whose density is one quarter the density of ambient air. Helium is virtually insoluble in human tissues at atmospheric conditions. In addition, helium is nonreactive with biologic membranes and other common respiratory gases. Iii At 1 atmosphere, longterm inhalation of helium-oxygen mixtures has failed to show any deleterious effects. 19 As a result of its lower density, helium has a larger binary diffusion coefficient for carbon dioxide when compared to air. The addition of helium to other gases will enhance the diffusivity of the combination. 20 Mixtures of helium and oxygen are only slightly more viscous than air, although they possess a much larger kinematic viscosity due to their lower density (Table 2). Kinematic viscosity is the ratio of viscosity to density. Gases of equal kinematic viscosity will become turbulent at equal flow rates. Compared to nitrogen-oxygen mixtures, helium-oxygen mixtures should allow laminar conditions to persist at signifi-

cantly higher flow rates. 21 •22 The Reynolds nUlnber is the ratio of kinetic and viscous forces afTectin~ the airflo\v, and predicts \vhether the airflo\\r in a tuhe will he lalninar or turbulent. 23 For a ~iven set of ainvay dilnensions, turbulent flow has a greater resistance than larninar flow. Theoretically, turbulent flo\v is present \vhen the Reynolds numher exceeds 2,000 units. Under high flo\\r conditions in the hUlnan trachea and mainstelll bronchi, the Reynolds nUlllher is estiluated behveen 2,100 and 2,500 units. 24 Even under lo\\r flo\\' conditions, air ffiovelnent in the trachea is turbulent owin~ to the larynx and the irregular surface due to the cartilaginous rin~s.2.,)·26 It is probable that adherent nlUCUS and heter()~eneous hronchoconstriction in the decompensated asthlnatic further contribute to elevated airways resistance. 27 As a result of its reduced density, a substitution of helium for nitro~en as the carrier gas \\'ould reduce the Reynolds number finlrfold, leading to a change from predominantly turbulent to laminar flo\v. For a given drivin~ pressure, this substitution should be Inanifest as si~nificantly less density dependent flo\v-resistive forces, allo\\'ing greater 8o\v during inspiration and expiration. Similarly, this substitution should lead to a reduction in the 80\\' resistive work performed hy the patient or the ventilator. One of the causes of ineffective ventilation in mechanically ventilated asthmatic patients results from proximal airway pressure exceedin~ the Inaximum pressure linlits of the ventilator causing the apparatus to recycle. This phenomena leads to slualler tidal volumes than expected, resulting in alveolar hypoventilation. The increase in larninar flo\v in concert \\'ith reduction in internal ainvay resistance \vhile breathing helium-oxy~en rnixtures enables lar~er tidal volumes and larger inspiratory 80\\'s for any ~iven set of ventilatory parameters. Experiruentall}~ our data demonstrate a statistically and clinically significant reduction in PC()2 (35.7 ± 9.5 n1m Hg); reduction in proximal ainvay pressure (32.7 ± 12.7 cm H 20); and a elevation of pH (0.30 ± 0.06 units). Pulmonary ~as exchange during periods ofbreathin~ variable density gas is not entirely understood. LOIl-

Table 2- Physical Properties of Respiratory Gases

OXYJ?;en Air Helium He-02 He-O:2 He-O:2

%/%

Density

y'Density

Vis<"'osity

Kineruatic Viscosity

100 100 100 20/80 40/60 80/20

1.429 1.293 0.179 1.178 0.678 0.429

1.182 1.135 0.423 1.085 0.823 0.655

211.4 188.5 201.75 209.5 207.5 203.6

147.9 145.8 1127.1 177.R 306.1 474.6

Ht"lalivt"

FI.)w Halt"* 0.96 1.00 2.68 1.04 1.3H

2.06

*Air assi~ned arbitrary value of 1.00. Viscosity measured in mieropoise. CHEST I 98 I 3 I SEPTEMBER, 1990

695

gitudinal mlxmg of respiratory gas occurs though a combination of convective and diffusive transfer. 2H However, the convective mediated component of transport is eliminated hy hreath holding. 29 Several investigators have shown that convective and diffusive forces interact to mix inspired and alveolar gas during inspiration.:~I':12 Convective forces dominate in conducting airways; diffusive forces dominate in the small airways. In the intermediate airways, a "front" is propagated where the forces meet, causing a sharp concentration gradient at which mixing of alveolar and inspiratory gases predominate. The dissipation of energy at the front enables facilitated diffusion. A theoretic model has been developed to

help explain the complex interaction of convection and diffusion in the heterogeneous lung (Fig 2).33,34 In status asthmaticus, diffuse bronchoconstriction increases stratification inhomogeneity producing a heterogeneous population of ventilation/perfusion units. Increased ventilatory effort may enhance convective forces penetrating narrowed airways, thus preserving inspiratory and alveolar gas mixing at the expense of increased work ofbreathing. With the onset of fatigue, severely constricted airways would remain poorly ventilated, depending on diffusive forces for mixing. A substitution of helium for nitrogen would enhance both convective and diffusive forces, effectively recruiting low V/Q units. Thus, facilitated dif-

FI(;[IIIE 2. A. liP/WI' hit: Under normal Cluiet hreathing mnditions. convective and diffusive forces are halanced. The dissipation on enerl-.')' at the interface of convective and diffusive forces augments gas mixing. Cas transport and alveolar gas mixing are equally dependent on convection and diffusion, B. upper right: Under l1lnditions of hronduK"nstrietion, airways are narrowed aeeentuating penetration of the wave "front" d....pt·r into distal hronchiol..s preserving facilitated diffusion at the expense of increased work of hreathing. Alveolar gas mixing is primarily dependent on overall ventilation. C, lower left: With the onset o£fatigue. ventilation 1lt'<."llles less efficient, and gas transport and alveolar gas mixin/-l becomes dependent on diffusive ",rc..s. D, [ou'n' right: The suhstitulion of helium for nitrogen as the earrier /-las provides incr..as..d laminar flow and distal respiratory unit penetration, as well as reducin/-l the diffusion distance "Ir CO,. Additionally, facilitated diffusion is enhanced.

696

Gas Mixtures in Intubated Patients (Gluck, Onorato. Csstriotts)

fusion would be enhanced and the inhomogeneity of ventilation would be reduced. Moreover, helium may enhance transport through collateral ventilation. 35 Under conditions of sustained inspiratory loading, increases in FRC have been noted. 36 Patients who are in extremis from status asthmaticus likely have an increased FRC from inspiratory and expiratory resistive loading. It is possible that helium-oxygen breathing under these conditions would cause a reduction in FRC. Thus, respiratory muscles would have a mechanical advantage while simultaneously reducing resistive load. Since patients with respiratory failure and hypercapnia are on the steep portion of the alveolar ventilation VS CO2 asymptote, a small increase in alveolar ventilation would result in a significant reduction in Pco2 • It is also interesting to consider the effect helium has on equal pressure points. During a forced expiration, airway and pleural pressures approximate each other, generating an equal pressure point. Mouthward, a How-limiting segment is propagated. Flow on the upstream segment, between the alveolus and the equal pressure point, is laminar and dependent on viscosity. Flow between the equal pressure point and the Bow-limiting segment is turbulent, and densitydependent. Helium-oxygen mixtures move the EPP upstream, without altering the position of the FLS. 37.3Ii A more upstream position of the EPP would result in an increase in the cross-sectional area of the lung that is density dependent. Increasing the area of density dependent lung, while simultaneously breathing a low density gas, should combine to reduce the total airway resistance and increase maximum expiratory flo~ This has been demonstrated in excised human lungs. 39 In bronchoconstricted airways, a wide distribution of time constants accentuates the pendeluft effect resulting in a uneven ventilation and perfusion. The substitution of helium for nitrogen should normalize time constants and produce a more uniform ventilation/perfusion ratio. Still, in patients with significant airflow obstruction, there is evidence to suggest that the pleural pressure time constants may be different from normal patients. 4o Breathing helium-oxygen mixtures may normalize the difference between airway and pleural pressure time constants, thus facilitating removal of alveolar gas. Since the reduction in peak airway pressures, the increase in tidal volume, and the reduction in inspiratory/expiratory ratios all were manifest within the first two minutes in all patients after the transfer to the helium-oxygen mixtures, it is unlikely that the previously administered medication caused this effect. In fact, one patient who had failed a trial of halothane anesthesia, promptly responded to ventilation with heliox. In our trial, we relate our experience in seven

intubated patients in whom severe status asthmaticus and respiratory acidosis were resistant to a~ressive medical management, but prolnptly responded to the addition of helium-oxygen blends. Although the sample size is small, we have demonstrated a statistically and clinically significant reduction in Pco 2 and peak airway pressures while breathing heliuln-oxy~en mixtures. In all patients, tidal volume and inspiratory How rates while breathing helium were able to be increased. There were no untoward effects. Helium's therapeutic benefit is related to its high kinematic viscosity, high binary diffusion coefficient, ]0\\' density, and the subsequent effects of these properties on airway resistance and facilitated diffusion. On practical and on theorectic grounds, the utility ofhelium-oxygen mixtures to reduce barotrauma and improve ventilation represents a beneficial addition to the conventional therapeutic armamentarium. REFERENCES 1 Benatar SR. Fatal asthma. N EnJtI J Med 1986; 314:423-28 2 Robin ED. Death from bronchial asthma. Chest 1988; 93:61420 3 McFadden ER, Austen KF. Asthma. In: Petersdorf RG, Adams RD, Braunwald E, Isselhacher Kj, Martin JB, Wilson jD. eds. Principals of internal medicine. 10th Ed. Ne\\' )(>rk: ~tc(;raw­ Hill, 1983:1512-19 4 Mountain RD. Sahn S. The clinical nutcolne in ~dients ,,'ith acute asthma presentin~ with hypercapnia. Am Rev Respir Dis 1988; 138:535-39 5 Shnider SM, Papper EM. Anesthesia for the asthlnatic patient. Anesthesiolo~ 1961; 22:886-89 6 O'Rourke p~ Crone RIC Halothane in status asthrnaticus. Crit Care Moo 1982; 10:341-43 7 Barach AL. Use of helium as a new therapeutic ~as. Proc Soc Exp BioI Med 1934; 32:462-64 8 Barach AL. The use of helium in the treatment of ,\stI1lna and obstructive lesions of the larynx Clnd trachea. Ann Intern Med 1935; 9:739-65 9 Barach AL. The therapeutic use of helium. JA~tA 1936; 107: 1273-75 10 Barach AL. The use of helium as ,\ new therapeutic J,tas. Anesthesia Analg 1935; 14:210-15 11 Bullen SS Sr. Correlation of clinical and autopsy findin~s in 176 cases of asthma. j Aller~' 1952; 23:193-203 12 Mirzrah S, Yarri Y. Lugassy G, Cotev S. ~faj()r airway ohstruction relieved by helium-()xy~entherapy. erit Care Med 1986; 14:986-

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Gas Mixtures in Intubated Patients (Gluck, Onorato, Castriotta)