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(Chest. 2004;126:1134-1137.)
© 2004 American College of Chest Physicians

How Do Patients Determine That Their Metered-Dose Inhaler Is Empty?*

Bruce K. Rubin, MD, MEngr, FCCP and Lolly Durotoye

* From the Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to: Bruce K. Rubin, MD, MEngr, FCCP, Professor and Vice Chair, Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Blvd, Winston Salem, NC 27157; e-mail: brubin{at}wfubmc.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: To evaluate how patients determined that pressurized metered-dose inhaler (pMDI) canisters were empty and to measure pMDI depletion under different circumstances in the laboratory.

Setting: Most of the study was performed in a university research laboratory.

Participants: Fifty consecutive patients attending the Brenner Children’s Hospital Asthma Center were initially questioned regarding pMDI use, and they demonstrated their use of the inhaler.

Measurements and results: Of the 50 children and parents questioned, 74% did not know how many actuations were in their canisters, and all used their pMDI until they could not longer "hear" the medication when actuating. Only half shook the canister before actuating. In the laboratory, chlorofluorocarbon (CFC) canisters typically had 86% more actuations than the nominal dose, and hydrofluoroalkane (HFA) canisters had 52% more. Canister flotation was ineffective in identifying when a pMDI was depleted, and water obstructed the valve opening 27% of the time. For CFC inhalers, shaking the pMDI before firing increased the number of actuations per canister (p = 0.009 [vs not shaking]), but this was not true for HFA inhalers.

Conclusions: If patients are not taught to recognize when a pMDI is empty, they may continue to use the medication for up to twice the intended duration. Until accurate dose counters are added to pMDIs, counting the number of doses administered is the only accurate method with which to tell when the canister should be discarded.

Key Words: adherence • aerosol therapy • asthma medication • dose counters • hydrofluoroalkane propellants • pressurized metered-dose aerosol


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
There are many factors that can adversely influence the effectiveness of aerosol therapy.1 Among these is the misuse of medication. Patients may rely on inaccurate methods of determining whether a pressurized metered-dose inhaler (pMDI) canister is depleted, such as by shaking the inhalers or estimating the weight of the canisters. In one study,2 54% of patients surveyed were unaware of the maximum number of actuations listed by the manufacturer for the pMDIs they were using, and only 8% reported counting the number of actuations used. Only 15% of health-care providers and 17% of asthma patients could describe how to estimate the amount of medicine left in the canister.3

Although canister flotation in water has been suggested as a way to determine when a medication canister is depleted, there seems to be no single flotation pattern that accurately reflects when pMDI canisters have exhausted their specified maximum number of actuations.4567 Flotation characteristics have been reported to be product-specific, and are a function of canister size, design, content, and method of testing. An additional problem is that flotation may introduce water into the neck of the actuation valve, reducing the medication output.

Another problem that has been noted is that many patients do not shake the pMDI canister before each actuation.38 In an earlier study,8 it was found that not shaking the MDI before use reduced the total and "respirable" medication dose delivered to a test lung by 25.5% and 35.7%, respectively.

The specific aims of this study were (1) to examine the patient’s understanding of when a pMDI canister contains medication and when it is depleted, (2) to evaluate whether the flotation pattern of pMDI canisters at different stages of depletion is an accurate means of assessing the degree of emptying and to determine the frequency with which pMDI canister valves are affected by water immersion, (3) to determine the total number of "puffs" per canister by auditory assessment and how this relates to the nominal contents stated by the manufacturer, and (4) to evaluate the effect of pMDI canister shaking on the rate of pMDI depletion


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patient Survey
Fifty new patients who regularly used pMDI medications were identified in the asthma clinic of the Brenner Children’s Hospital at Wake Forest University. As part of our asthma education program, each patient and/or parent was asked the question, "How do you know when it is time to replace your inhaler?" Subjects were asked to elaborate on answers that were unclear, such as how they interpreted floating patterns of water-immersed pMDI canisters or how they suspected that a canister no longer held medication.

pMDI Canisters and Actuation
We obtained samples of the following pMDI canisters from the manufacturer:

  1. Fluticasone propionate (Flovent 44 [12 canisters], Flovent 110 [9 patients], and Flovent 220 [13 canisters]; GlaxoSmithKline; Research Triangle Park, NC). Each canister contained 60 actuations, according to the manufacturer.
  2. Salmeterol xinafoate (Serevent [12 canisters]; GlaxoSmithKline). Each canister contained 60 actuations, according to the manufacturer.
  3. Albuterol (Ventolin [4 canisters]; GlaxoSmithKline). Each canister contained 80 actuations, according to the manufacturer.
  4. Beclomethasone dipropionate (hydrofluoroalkane [HFA]-QVAR 40 [4 canisters] and QVAR 80 [3 canisters]; 3M Pharmaceutical Division; St Paul, MN). Each canister contained 100 actuations, according to the manufacturer.

These were sequentially emptied of their contents by actuation. We had a 10-s pause between each manual actuation. Half of the canisters were shaken five times before each actuation, while the others were fired without shaking. A 20% "overfill" was assumed for each canister (Dr. C. Crim, GlaxoSmithKline; personal communication). We weighed canisters at each stage of emptying, as follows: full; half empty, based on the nominal number of actuations; "empty," as defined by the manufacturer; empty plus 20%; and until no sound was heard with actuation. The absence of a sound with actuation was confirmed by both investigators.

Flotation
We evaluated how each canister floated when new, half empty, and empty based on the nominal dose specified by the manufacturer. The canisters then were actuated and weighed after an additional 20% of the nominal dose, and finally until there was no longer an audible release of aerosol. Canisters were immersed in a clear Plexiglas tank, and digital photography was used to capture the image of the canister, then the angle of flotation at each level of emptying was measured (salmeterol, three canisters; Flovent 44, three canisters; Flovent 110, three canisters; and Flovent 220, three canisters). We determined how frequently the canister valve became obstructed by water during flotation by the direct examination of the canister valve nozzle using a dissecting microscope. This examination was performed after each flotation. For consistency, canister valves were always air-dried after each water immersion.

Statistical Analysis
The statistical analysis of data was performed using a statistical software package (StatView, version 5; SAS Institute; Cary, NC) to determine the relationships among flotation angle, medication type, and degree of emptying as well as the variability among different canisters of the same medication and frequency of valve obstruction, and whether canister shaking affected the pMDI medication output.

All pMDI canisters were compared only with canisters of the same drug and dosage. Based on preliminary data (not shown), this study was powered to detect a 25% difference in actuations heard compared with the nominal number of actuations with 85% confidence and an {alpha} of 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Survey Results
We found that 36 subjects (72%) determined that a canister was out of medication when they could no longer hear the canister make a sound when actuated. Ten subjects said that they replaced the canister when it was "old," but none gave a precise time for replacement. The most frequent answers were "after a month or so" (four patients) or "after a while" (three patients). Four patients said that they were supposed to float the canister, and all four stated that they were told that the canister would sink to the bottom when there was still medication but would float on top when empty. None of these four patients had actually ever used the flotation technique.

We also found that although 78% of patients knew that they were supposed to shake the canister before each actuation, when later asked to demonstrate the use of the pMDI only half (25 patients) first shook the canister before actuating.

Flotation Results
All pMDI canisters that were evaluated had similar flotation patterns (Fig 1 ). The mean (± SD) flotation angles in water when fully depleted ranged from 27.6 ± 0.96° for Ventolin to 31.7 ± 0.65° for Serevent, with all Flovent canisters falling between these values. Water obstructed the valve or collected near the valve 27% of the time (13 of 48 times) when the canisters were floated.



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  		Figure 1.. The flotation pattern of a pMDI in water. All canisters sunk to the bottom when full but floated upright even when 50% of the nominal dose was used. The mean flotation angles in water when fully depleted ranged from 27.6 ± 0.96° for Ventolin to 31.7 ± 0.65° for Serevent, with all Flovent canisters falling between these values.

 
Canister Depletion and the Effect of Shaking the Canister
Overall, the chlorofluorocarbon (CFC) propellant canisters (ie, Ventolin, Serevent, and Flovent) had a mean of 86 ± 14% more audible puffs than the maximum number stated by the manufacturer, and the HFA canisters (QVAR) had a mean of 54 ± 16% more puffs (Table 1 ). In general, shaking the canister increased the total number of medication doses available until pMDI depletion. The number of actuations (shaken vs not shaken) for Flovent was 116 vs 108, respectively (p = 0.0027), for QVAR the difference was not significant, for albuterol was 171 vs 125, respectively (p = 0.01), and for salmeterol was 113 vs 109, respectively (p = 0.048).


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  		Table 1.. Canister Actuations Until Depletion*

 
The change in weight of a piece of filter paper that was 5 cm in diameter was determined after actuation and drying. The aerosol solid mass remaining on the filter paper was used as a surrogate measure for the medication dose emitted. The amount of medication on the paper was not directly determined. The pMDI was fired in a fume hood from a distance of 3 cm directly onto a completely dry filter paper at the bottom of a glass funnel. This paper then was air dried in a desiccant jar. Canister shaking before actuation had a variable effect on the medication solids on the filter, as shown in Figure 2. For CFC pMDIs, shaking increased the amount of drug deposited on the filter (p = 0.009), but there was no difference in drug deposited for the HFA inhalers (p = 0.83).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this study, we surveyed patients using pMDI inhalers to determine their methods for deciding when to replace an inhaler. We also determined the number of actuations remaining in inhalers beyond the specified number listed by the manufacturer and progressively assessed the flotation status of the inhalers during pMDI canister depletion. We also evaluated the effect of always or never shaking the canister before actuation on the number of actuations remaining in inhalers beyond the nominal dose and on the amount of aerosol-derived solid mass deposited on a filter paper during the process of pMDI depletion.

All canisters that were tested contained a much greater number of total actuations than the number listed by the manufacturer. CFC propellant-based canisters had about 86% more audible puffs than the maximum number stated by the manufacturer, and HFA canisters had 54% more. The patient survey indicated that this misunderstanding was a major source of medication misuse. We have termed this practice pseudo-adherence.

There was no universal flotation status that accurately showed when pMDI canisters had reached their specified maximum number of doses. These data are consistent with those of previous studies.4567 Because of this, the National Asthma Education and Prevention Program recommended that the only reliable method for determining the number of doses remaining in a canister is to subtract the number of doses used from the number available. It has further been recommended that all asthma inhalers should be discarded at the discard point labeled on the canister or box. In this study, we also have shown that the practice of flotation to determine the amount of medication remaining in a pMDI is potentially dangerous, as over one quarter of the time this led to water collecting at the top of the valve stem.

Everard and colleagues8 have shown that not shaking a CFC propellant pMDI before use reduced the total medication dose delivered to a test lung by 25.5%, and reduced the respirable dose by 35.7%. They also showed that storing the pMDI stem-down reduced the total dose delivered in the first actuation by 25.0% despite shaking the MDI before use. Our data for CFC inhalers are consistent with this, and we have shown that this problem persists at all levels of pMDI depletion. However, our limited data suggest that HFA beclomethasone inhalers (QVAR) were less influenced by shaking than were the CFC inhalers.

Patients are rarely instructed that it is important to count the number of doses used throughout the life of a pMDI inhaler and to discard the inhaler once the stated maximum number of puffs are used. Furthermore, for medications taken only as needed, counting doses is likely to be difficult and inaccurate. An accurate, effective, and inexpensive means of dose counting is important. Devices with built-in dose counters, such as some dry powder inhalers, can have a great impact on the effectiveness of aerosol drug delivery. Electronic "chronologs" have been developed for dose counting, but these are notoriously inaccurate. In one study,9 only 10 of 24 chronolog units were rated as acceptable after > 8 days when using generous criteria for acceptable reliability. Another study10 determined that the accuracy of a chronolog in recording the number of actuations varied between 50% and 100%, and the authors concluded that these were not sufficiently reliable for clinical use. Aside from problems with accuracy, these devices add considerably to the cost of pMDIs.

We measured the amount of aerosol-derived solid mass that was deposited on a filter paper, but we did not directly measure the amount of the different medications that was deposited. Although there was a falloff in the amount of solid mass observed on the filter paper as the canisters were emptied, it will be very important to determine to what extent these solids contain active medication.

If patients are not taught to recognize when a pMDI is empty, they may continue to use the medication canister long past its intended duration of use. Until effective dose counters are added to pMDI inhalers, counting the number of doses administered is the only accurate method with which to tell when the canister should be discarded.


   Footnotes
 
Abbreviations: CFC = chlorofluorocarbon; HFA = hydrofluoroalkane; pMDI = pressurized metered-dose inhaler

Received for publication July 24, 2003. Accepted for publication April 30, 2004.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Rubin, BK (2004) What does it mean when the patient says, "My asthma medicine isn’t working"? Chest 126,972-981[Free Full Text]
  2. Ogren, RA, Baldwin, JL, Simon, RA How patients determine when to replace their metered-dose inhalers. Ann Allergy Asthma Immunol 1995;75,485-489[Medline]
  3. Jones, JS, Holstege, CP, Riekse, R, et al Metered-dose inhalers: do emergency health care providers know what to teach? Ann Emerg Med 1995;26,308-311[CrossRef][Medline]
  4. Wolf, BL, Cochran, KR Floating patterns of metered dose inhalers. J Asthma 1997;34,433-436[Medline]
  5. Cain, WT, Oppenheimer, JJ The misconception of using floating patterns as an accurate means of measuring the contents of metered-dose inhaler devices. Ann Allergy Asthma Immunol 2001;87,417-419[ISI][Medline]
  6. Brock, TP, Wessell, AM, Williams, DM, et al Accuracy of float testing for metered-dose inhaler canisters. J Am Pharm Assoc 2002;42,582-586[Medline]
  7. Weinstein, AG When should your asthmatic patients refill their MDI propelled with chlorofluorocarbons? Del Med J 1998;70,293-297[Medline]
  8. Everard, ML, Devadason, SG, Summers, QA, et al Factors affecting total and "respirable" dose delivered by a salbutamol metered dose inhaler. Thorax 1995;50,746-749[Abstract]
  9. Brueckner, JW, Marshik, P, Sherman, J, et al Reliability of the Medtrac MDI Chronolog. J Allergy Clin Immunol 1997;100,488-491[Medline]
  10. Wamboldt, FS, Bender, BG, O’Connor, SL, et al Reliability of the model MC-311 MDI Chronolog. J Allergy Clin Immunol 1999;104,53-57[Medline]



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Counting inhaler doses
.Karen S D Robinson
Chest Online, 22 Nov 2005 [Full text]
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