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Anesth Analg 2001;92:379-383
© 2001 International Anesthesia Research Society

TECHNOLOGY, COMPUTING, AND SIMULATION

Canister Tip Orientation and Residual Volume Have Significant Impact on the Dose of Benzocaine Delivered by Hurricaine® Spray

Arjang Khorasani, MD*{dagger}{ddagger}, Kenneth D. Candido, MD{dagger}{ddagger}, Ahmed H. Ghaleb, MD{dagger}, Simin Saatee, MD{dagger}{ddagger}, and Samuel K. Appavu, MD§

*Division of Critical Care Anesthesiology and {dagger}Department of Anesthesiology & Pain Management, Cook County Hospital; {ddagger}Department of Anesthesiology, Rush-Presbyterian-St. Luke’s Medical Center; and §Division of Surgical Critical Care, Cook County Hospital, and Department of Surgery, University of Illinois College of Medicine at Chicago, Chicago, Illinois

Address correspondence and reprint requests to Arjang Khorasani, MD, Department of Anesthesiology & Pain Management, Cook County Hospital, 1835 W. Harrison St., Chicago, IL 60612. Address e-mail to arjangk{at}SPHK.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Delivered quantities of 20% benzocaine spray (Hurricaine®; Beutlich L.P. Pharmaceuticals, Waukegan, IL) are estimated by counting the number of sprays or the spraying time. Because Hurricaine spray supplies a continuous (albeit nonmetered) stream of benzocaine, neither method addresses delivered dose. We hypothesized that dose per time is a function of canister content and orientation. Thirty full canisters of Hurricaine were placed into three equal orientations (upright, inverted, or horizontal). Extrapolating from a full canister, four different estimates of benzocaine residual volume were determined before spraying out the contents (80%, 60%, 40%, and 20% full). Each canister was then sprayed for 10-s intervals, and the quantity delivered was calculated and compared statistically. Upright canisters 100% full emitted more benzocaine than canisters with residual volume 20% full (190 ± 10 vs 172 ± 10 mg/s). Inverted canisters emitted significantly less benzocaine from 100% full to residual volume 20% full (188 ± 14 vs 70 ± 10 mg/s). Oriented horizontally, two full canisters emitted <76 mg/s benzocaine, contrasted with the remaining eight in that group (186 ± 20 mg/s). We conclude that the benzocaine (Hurricaine) sprayed in milligrams per second depends on canister content and orientation. When residual volumes diminish, there is a reduction in spraying volume per time. This diminution occurs progressively from larger to smaller residual volumes with canisters oriented horizontally, inverted, or upright. Arbitrary documentation of spraying time bears no relationship to dose delivered. Perhaps affixing an atomization device to a graduated syringe filled with benzocaine will help increase accuracy and precision in dosing.

Implications: There is substantial variability in dose of benzocaine administered by nonmetered Hurricaine® spray. Canister orientation and residual volume of anesthetic significantly affect output of benzocaine and are clinically uncontrollable. Methemoglobinemia may occur even after the manufacturer’s suggested spraying guidelines. We saw no correlation between dose and spraying time or number of sprays.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Benzocaine spray (Hurricaine®; Beutlich L.P. Pharmaceuticals, Waukegan, IL) is used to provide topical anesthesia. Because it is a nonmetered preparation, the delivered amount of benzocaine has been estimated by counting the number of sprays (1) or, conventionally, by duration, i.e., the "sprayed time in seconds" (2). Neither of these methods has satisfactorily addressed the issue of quantity delivered.

There is no agreement in the literature regarding the delivered amount of benzocaine emitted per spray or per second of spraying time of Hurricaine. There is enormous variability, with published reports of benzocaine being delivered in amounts as small as 60 mg/s (2) or as large as 3300 mg/spray (3). Also, the effect of the Hurricaine canister’s residual content and spray tip orientation in relationship to a planar surface on the delivered dose of benzocaine has never been reported. Therefore, we examined the effect of these variables on the amount of benzocaine delivered.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Thirty full canisters of Hurricaine were randomly selected for study, with 10 canisters each placed into one of the three orientation categories (upright, inverted, or horizontal). Group A consisted of canisters held upright (n = 10). Group B consisted of canisters held in an inverted position (n = 10). Group C consisted of canisters held horizontal to a planar surface (n = 10). A full canister of Hurricaine had been determined during the preliminary part of the current study to weigh approximately 79.7 ± 0.9 g. The tare weight of the canister is approximately 21.7 ± 0.2 g, leaving a net weight of 58.0 ± 0.6 g of solution (benzocaine, denatured alcohol, polyethylene glycol, and sodium saccharin) (4). The specific gravity of Hurricaine has been determined by Beutlich Pharmaceuticals LP to be equal to 1 (4).

We extrapolated from the average weight of the full Hurricaine canister (79.7 g) as well as the average net weight of the solution (58.0 g) to determine four different estimates of residual solution present in each canister before spraying: 80%, 60%, 40%, and 20% full. All canisters (full and after spraying) were weighed on a digital scale (Mettler Balance model PE 3600; Mettler Instrument Corp, Highstown, NJ) that has a readability of 0.01 g. These weights (solution plus canister) corresponded approximately to 68.1 g (79.7 - 0.2 x 58.0), 56.5 g (79.7 - 0.4 x 58.0), 44.9 g (79.7 - 0.6 x 58.0), and 33.3 g (79.7 - 0.8 x 58.0), respectively. This was done to estimate the requisite residual content of a Hurricaine canister before study. We next sprayed each canister continuously for 10-s intervals to estimate the quantity of delivered solution on the basis of its starting volume. This was done for each canister in each of the three orientation groups (A, B, and C). The sprayed amount of Hurricaine in 10-s intervals from five predetermined residual volumes in each of the three orientation groups was calculated from the weight of solution and compared with statistical analysis ( Table 1).


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  		Table 1. Effect of Canister Orientation and Residual Volume on Emitted Milliliters of Hurricaine® per 10 s of Spraying
 
Our preliminary study demonstrated that the sprayed amount of Hurricaine in 10-s intervals for a full canister in an upright position is 9.5 ± 0.5 mL. During this study, it became evident that some canisters could not be emptied completely in orientations other than upright. It was also evident that even with residual solution in the canister, there was extreme variability in the emitted volume. On the basis of these findings, we categorized the following three canister scenarios:

  1. 1. Empty canister: the canister was considered empty if shaking the canister demonstrated a lack of residual liquid in the canister.
  2. 2. Spraying failure: the canister was considered to be a spraying failure if shaking the canister confirmed the presence of a liquid in the canister, which, however, emitted <1 mL per 10 s when the residual estimated content of the canister before spraying was 40% or less, compared with full.
  3. 3. Canister malfunction: the canister was considered to malfunction when the estimated residual content of the canister before spraying was 60% or more compared with full, which, however, sprayed out <40% of the average sprayed amount of a full Hurricaine canister over 10 s in an upright position (corresponding to 3.8 mL per 10 s).

We opened a Hurricaine canister to examine its internal structure and working parts. As shown in Figure 1, the manufacturer uses a ball-valve system to permit spraying of the liquid preparation with variable orientations of the canister in relationship to a planar surface. In the ball-valve system, when the canister is held upright, the rolling ball closes orifice A; hence, the pressurized gas in the canister forces the liquid to pass through orifice B, and solution courses through conducting tube C.



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  		Figure 1. Photograph of internal spraying structure of Hurricaine® spray showing the ball-valve apparatus.

 
The solution can be sprayed when someone opens the proximal end of tube C by depressing the spring-loaded valve D ( Fig. 2). In the inverted position, the ball will move away from orifice A, leaving the orifice open (Figs. 1 and 2). Consequently, when the spring-loaded valve D is opened, the pressurized gas will cause the solution to enter tube C through orifice A. As shown in Figures 1 and 2, the ball valve and tube C are displaced more than 5 mm off the center of the canister. Unless otherwise specified, values are expressed as mean ± SD. Statistical comparison among groups was performed with analysis of variance, Student’s t-test, and the Bonferroni modification for multiple comparisons. Differences were considered significant at P < 0.05.



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  		Figure 2. Photograph of internal spraying structure of Hurricaine® canister with and without cross-section of the canister. A, Orifice A. B, Orifice B. C, Tube C. D, Spring-loaded valve D. A 10-mm ruler is placed next to orifice A, showing approximately a 5-mm off-center displacement of tube C, orifice A, and the rolling ball. Bottom, The rolling ball closing orifice A. Top, The rolling ball has moved away from orifice A, leaving the orifice open.

 

   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
When full canisters of Hurricaine were held in the upright position (Group A) and sprayed continuously for 10 s, the average volume sprayed per second was 0.95 ± 0.05 mL, equal to delivering 190 ± 10 mg of benzocaine (range, 174–202 mg). There were no significant differences in the sprayed volume of Hurricaine during any 10-s interval with canisters held in the upright position as long as the residual volume in the canister remained more than 20% of the full canister. However, when the canister was allowed to empty to <20% of its full volume, there was a decrease in the sprayed quantity of Hurricaine over 10 s as compared with the full canister (Table 1). It was nevertheless possible to spray out the contents of each canister completely.

When full canisters of Hurricaine were held in the inverted position (Group B) and sprayed continuously for 10 s, the average volume sprayed per second was 0.94 ± 0.07 mL, equal to delivering 188 ± 14 mg of benzocaine (range, 164–212 mg). There were no statistically significant differences in the sprayed volume of Hurricaine over 10-s intervals with canisters held in the inverted position when the contents of the canister remained more than 20% full. However, there was a decrease in the sprayed volume of Hurricaine over 10 s when the starting contents of the canister were 20% full, as compared with when the canister was 100%, 80%, 60%, or 40% full (Table 1). As the volume in the canisters became <20% full, drug delivery decreased precipitously to the point that we were not able to spray out the entire contents of any of the canisters in Group B (spraying failure). The average estimated amount of residual Hurricaine that was unable to be sprayed was 7.4 ± 0.6 mL.

When full canisters were held in a horizontal position (Group C) and sprayed continuously for 10 s, the average volume sprayed per second was 0.93 ± 0.1 mL, equal to delivering 186 ± 20 mg of benzocaine (range, 160–210 mg). There were no statistically significant differences in the sprayed volume of Hurricaine over 10 s when canisters were held in a horizontal position as long as the contents of the canister remained more than 60% full. However, in two full canisters, canister malfunction was noted, and they were eliminated from the study (statistical analysis was performed for the eight remaining canisters). In the remaining eight canisters with contents 80% full, one canister malfunction occurred, and statistical analysis was subsequently performed on the seven remaining canisters. In one canister with residual content of 40% and in four of the six remaining canisters with residual contents of 20%, spraying failure occurred. Only two canisters with residual contents of 20% were able to spray more than 1 mL per 10 s. We were not able to spray out the full contents of any of the canisters in Group C. The average estimated amount of residual Hurricaine that was unable to be sprayed (spraying failure) for the remaining seven canisters in the study was 13.6 ± 4.6 mL.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Benzocaine-induced methemoglobinemia has been described after its use by various routes of administration, both legitimate and illicit (3,5–9). Development of methemoglobinemia is related to the total drug dose as well as to factors enhancing systemic absorption, such as breaks in the skin or mucous membranes, tissue hyperemia, prolonged contact time, and large concentrations of drug in the preparation (2). Hurricaine spray contains benzocaine in a 20% concentration. Severinghaus et al. (10) recommended to product suppliers that "all products containing benzocaine over 8% should carry suitable warning of the probability that methemoglobinemia will occur in proportion to dosage. Labels should provide information of the possible need for methylene blue treatment and the recommended dosage."

Benzocaine-induced methemoglobinemia may be caused by excessive dosing (11), but it can also occur after a one-second spray (12). Beutlich Pharmaceuticals LP recommends that when using their Hurricaine product, "Spray 1/2 s. Repeat if necessary." However, there is no agreement in the literature regarding a recommended safe spraying time for Hurricaine. Guertler and Pearce (13) demonstrated with their prospective human study a clinically insignificant increase in methemoglobin levels after two seconds of continuous Hurricaine spraying administered to the oropharynx of healthy adult volunteers and patients. However, they did not report the orientation and the residual content of the canister during the spraying.

There are problems with recommending an arbitrary spraying time. First, we find it virtually impossible in a clinical setting to be able to accurately spray for this brief one-second period. Second, we have shown that it is impossible to accurately gauge the volume of Hurricaine delivered in one second of spraying time, which will vary with the residual volume in the canister and the orientation of the canister with regard to a planar surface. The clinician may be forced to redirect the canister orientation multiple times during the same application of Hurricaine spray to successfully direct the local anesthetic to its intended sites. Third, Hurricaine spray is not administered as a metered dose, and because there is no consistency in the quantity of local anesthetic that can be delivered per unit time, the documentation of an arbitrary spraying time in the patient’s medical record bears no relevance to an administered dose in milligrams.

We were unable to completely empty Hurricaine canisters except when they were held upright. In an effort to determine the basis for our inability to discharge the contents of the canister completely when the device was held in a position other than upright (Groups B and C), we opened a Hurricaine canister (Figs. 1 and 2). With the canister in an inverted position, once the contents of the canister decrease to the extent that there is insufficient residual volume to reach orifice A, the remaining volume will not be accessible for spraying out of the canister. In this study, this volume was 7.4 ± 0.6 mL. In the horizontal position (Group C), once the contents of the canister have decreased to approximately 50% full, the residual volume will not reach either orifice A or B, with the result that the remaining contents of the canister cannot be discharged externally. However, as is shown in (Figs. 1 and 2), the ball valve and tube C are displaced more than 5 mm off the center of the canister. With a canister held in a horizontal position, this 5-mm off-center location of the ball valve and tube C may result in an inability to spray the liquid even in the presence of a residual content more than 50% full if the conduit stays above the liquid meniscus. Alternatively, it may result in the continuing ability to spray liquid even in the presence of residual content <50% if the ball valve and tube C stay immersed in the liquid. In this study, this volume (unsprayable) was 13.6 ± 4.6 mL instead of 50% of the estimated volume of a full canister. The reason for this discrepancy may be caused by the methods of our study or to inherent design flaws in the manufacturing of the Hurricaine canister delivery system. Because three canisters demonstrated canister malfunction and because the remaining volumes of these canisters were not included in our statistical evaluation, we may have actually underestimated the unsprayable volume.

We cannot be certain as to the real reason for a given canister’s canister malfunction. We may only speculate that the off-center location of tube C negatively influenced the emitted spray volume, because we were able to effectively spray liquid out of these canisters when they were held upright or in an inverted position.

Several devices are available for accurately quantifying the anesthetic dose of benzocaine administered, most notably a disposable mucosal atomizing device (MADTM; Wolfe Tory Medical, Inc, Salt Lake, UT). Such simple systems connect directly to graduated syringes that may be loaded with predetermined doses of benzocaine. Their use may assist clinicians in avoiding the overzealous and otherwise uncontrolled application of anesthetic spray for topicalizing a mucosal surface. Being position independent, they may negate the inconsistencies we have found when using Hurricaine spray in differing spatial orientations.

Perhaps using preparations of benzocaine in concentrations <20% would help prevent or minimize complications caused by unintended excessive dosing. Concentrations as small as 2.5% have proved to be clinically effective when benzocaine is administered topically (14). Whether or not using benzocaine in this dilute form would maintain its efficacy as an airway anesthetic remains to be seen.

In summary, Hurricaine spray, as it is currently prepared and manufactured, displays significant variability in the emitted quantity of benzocaine. There is no correlation between the dose of benzocaine administered and spraying time or number of sprays.

We have demonstrated the inconsistencies in the delivered quantities of Hurricaine spray emitted per second, especially when the orientation of the canister is not upright in relationship to a planar surface. Also, when the residual volume in the canister has reached 20% full, inconsistencies in the delivered amount of Hurricaine will appear even when the canisters are maintained in an upright orientation.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Clary B, Skaryak L, Tedder M, et al. Methemoglobinemia complicating topical anesthesia during bronchoscopic procedures. J Thorac Cardiovasc Surg 1997; 114: 293–5.[Free Full Text]
  2. Wilburn-Goo D, Lloyd LM. When patients become cyanotic: acquired methemoglobinemia. J Am Dent Assoc 1999; 130: 826–31.[Abstract/Free Full Text]
  3. Ellis FD, Seiler JG, Palmore MM. Methemoglobinemia: a complication after fiberoptic orotracheal intubation with benzocaine spray. J Bone Joint Surg Am 1995; 77: 937–9.[Free Full Text]
  4. Hurricaine® Spray [material safety data sheet]. Waukegan, IL: Beutlich LP Pharmaceutical; 1996.
  5. Ferraro-Borgida MJ, Mulhern SA, DeMeo MO, Bayer MJ. Methemoglobinemia from perineal application of an anesthetic cream. Ann Emerg Med 1996; 27: 785–8.[Web of Science][Medline]
  6. McKinney CD, Postiglione KF, Herold DA. Benzocaine-adultered street cocaine in association with methemoglobinemia. Clin Chem 1992; 38: 596–7.[Abstract/Free Full Text]
  7. Brown CM, Levy SA, Susann PW. Methemoglobinemia: life-threatening complication of endoscopy premedication. Am J Gastroenterol 1994; 89: 1108–9.[Web of Science][Medline]
  8. Rodriguez LF, Smolik LM, Zbehlik AJ. Benzocaine-induced methemoglobinemia: report of severe reaction and review of the literature. Ann Pharmacother 1994; 28: 643–9.[Abstract]
  9. Sherman JM, Smith K. Methemoglobinemia owing to rectal-probe lubrication. Am J Dis Child 1979; 133: 439–40.[Abstract/Free Full Text]
  10. Severinghaus JW, Xu F-D, Spellman MJ. Benzocaine and methemoglobinemia: recommended actions. Anesthesiology 1991; 74: 385–6.
  11. Smith RP, Olson MV. Drug-induced methemoglobinemia. Semin Hematol 1973; 10: 253–68.[Web of Science][Medline]
  12. Guerriero SE. Methemoglobinemia caused by topical benzocaine. Pharmacotherapy 1997; 17: 1038–40.[Web of Science][Medline]
  13. Guertler AT, Pearce WA. A prospective evaluation of benzocaine-associated methemoglobinemia in human beings. Ann Emerg Med 1994; 24: 626–30.[Web of Science][Medline]
  14. American Hospital Formulary Service. Local anesthetics. In: McEvoy GK, Litvak K, Welsh OH Jr, et al., eds. Drug information®. 42nd ed. Bethesda, MD: American Society of Health-System Pharmacists Inc, 2000:2548–9.
Accepted for publication October 17, 2000.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press