ClinicalComparison of OcularIrrigationFluids FollowingChemical Injury ROBERT D. HERR, MD,* GEORGE L. WHITE, JR, PHD,t KURT BERNHISEL, MD,* NICK MAMALIS, MD,t ERIC SWANSON, BS$ This study tested the hypothesis that four ocular irrigating solutions were equally Mating during copious Irrigation. We conducted a prospective, double-blind study of patients with chemical exposure to the eye. Each underwent cross-over irrigation with all of the followtng in random order: normal saline (MS), lactated Ringer’s (UT), normal saline adjusted to pH 7.4 with sodium bicarbonate (MS + Blcarb), and Balanced Saline Solution Plus (BSS Plus, Alcon laboratories, Fort Worth, TX). Compared with traditional MS and LR, MS + Bicarb tended to be more comfortable. BSS Plus was statistically superior (P < .05) to MS and preferred over LR and MS + Blcarb. Three patients demanded discontinuance of MS or MS + Blcarb infusions. All solutions had comparable normalization of conjunctival pH and degree of injection. Alternate solutions including BSS Plus should be considered for use in those patients whose poor tolerance to normal saline threatens to delay or interrupt eye irrigation following a chemical injury. (Am J Emerg Mad lggl;g:22B-231. Copyright 0 1991 by W.B. Saunders Company)

Chemical burns to the eye are serious ophthalmologic emergencies and must be treated immediately and appropriately. Extensive ocular irrigation must begin with the most readily available source of fluid. Patients who subsequently present to the emergency department often require additional irrigation. This is done with a readily available sterile solution such as normal saline. Our experience has shown that patients exhibit a wide range of tolerance to irrigation with normal saline. Some patients complain of excessive discomfort and request that the ocular infusion be slowed or stopped. This discomfort is refractory to repeated instillation of topical anesthetic. Whereas normal saline has been a customary irrigant in our department, we sought to study if osmotic and pH-balanced solutions might prove more comfortable, better tolerated, but as effective as normal saline. The solutions we chose to compare were normal saline (NS), lactated Ringer’s (LR), normal saline with bicarbonate added (NS + Bicarb), and Balanced Saline Solution Plus (BSS Plus, Alcon, Fort Worth, TX). The pH, osmolality, and constituents of these

From the ‘Division of Emergency Medicine, Department of Surgery, and the TDepartment of Ophthalmology, SUniversity of Utah Medical School, Salt Lake City, UT. Manuscript received August 8, 1990; revision accepted November 30, 1990. Presented as a poster at the Society for Academic Emergency Medicine, Minneapolis, MN, May 23, 1990. Accepted for a poster at EMRYSAEM Combined Meeting, Edinburgh, Scotland, October 20, 1990. Address reprint requests to Dr Herr, Division of Emergency Medicine, University of Utah Hospital, 50 N Medical Dr, Salt Lake City, UT 84132. Key Words: Chemical conjunctivitis, irrigation, ocular injury. Copyright 0 1991 by W.B. Saunders Company 0735-6757/91/0903-0006$500/O 228

solutions are listed (Table 1). This study was approved by the Human Studies Committee at the University of Utah. MATERIALSAND METHODS We enrolled consecutive adult patients presenting to the University of Utah Emergency Department who required emergency eye irrigation after chemical exposure. The study continued from July, 1989 until the bottles of BSS Plus ran out in December, 1989. Patients were excluded if mental impairment precluded their determination of eye comfort. To avoid delay in initiating irrigation, informed consent was obtained verbally, usually as the patient was being escorted to the treatment room. Each patient had initial eye inspection for chemical particulate matter. The conjunctival pH and degree of injection was noted prior to and following each bottle of irrigant. The patient was laid recumbent, topical proparacaine (Alcaine, Alcon L) was instilled, and a Mediflow lens (Morgan therapeutic lens, MorTan Inc, Torrington, WY) was inserted. A 500 mL bottle of fluid was chosen at random and run through intravenous (IV) tubing at a wide open rate. After approximately five minutes, the patient was asked “How does your eye feel?” Responses were recorded. The patient was then asked to rank discomfort from 0 (none) to 10 (worst imaginable). After the infusion finished, pH and injection were determined, and another bottle was chosen in a random order. This was continued until all four different bottles were infused. The patient was then asked to rank in preference all four bottles from 1 to 4. Ties were accorded an average of the rankings. The first four patients were not asked to rate discomfort; this was asked to the last seven patients. All were clear solutions in identical 500 mL bottles. The labels were covered to hide their identities. All personnel were blinded to the bottles’ identities except the person preparing the solutions, who did not participate further in the trial. If requested by the patient, the infusate was stopped and another begun. Conjunctival pH was measured by “litmus” paper (pHydrion Papers, Micro Essential Laboratory, Brooklyn, NY). Injection was graded by the following scale: 0, normal pattern of vessels; 1, mild injection, no chemosis; 2, moderate injection or chemosis; 3, severe injection and chemosis. NS + Bicarb was prepared by adding 0.2 mL of a 1 mEq/mL bicarbonate solution to a 500 mL bottle of NS. This quantity of bicarbonate had been determined by pH meter titrations of three bottles to raise the pH of NS from 5.95 to 6.0 to approximately physiological pH for the conjunctival tear film, 7.4. All bottles were from the same lot number to minimize pH differences. Therefore, whereas the reported range of pH of NS is from 4.5 to 7.2, we believe these bottles to represent a narrower pH range.

HERR ET AL n COMPARISON OF OCULAR IRRIGATION FLUID

TABLE1.

229

Chemical Composition of Tear Film, Aqueous Humor, and Ocular Irrigation Fluids

Fluid Tear film”

Aqueous humor NS (pH depends on lot no.) NS + bicarb, 0.2 ml 1 mEq/ml sol’n LR (pH depends on lot no.)

BSS Plus solution

PH

Osmolality (m0sm)

7.4 (range: 7.3-7.7)

318

7.38 4.5-7.2 Approx. 7.4

304 290 290

6.0-7.2

277

7.4

305

BSS Plus was obtained from Alcon. It is reconstituted prior to use by adding a 20 mL vial of concentrate to a 480 mL bottle of solution. NS and LR were obtained from American Hospital Supply in 500 mL bottles. Discomfort ratings were compared using analysis of variance (ANOVA). If the ANOVA was significant, paired ttests with the Bonferroni correction were used to determine pairwise differences. Rankings (from 1 to 4) were compared using the Friedman test. If the Friedman test was significant, paired Wilcoxon tests with the Bonferroni correction were used to determine pairwise difference. All determinations of the type II error are expressed as sample size using 90% power (one sided) to find a difference of 1.0 in ranking or 1.0 in discomfort (at the P < .05significance level). RESULTS Eleven patients and a total of 12 eyes underwent irrigation, each with a single round of all four solutions. The types of chemical exposures encountered were as follows: alkali, 5 (potassium hydroxide, unknown cleaner [to both eyes], ammonia, ammonium chloride); phenol and ethanol, trichloroethane (Liquid Paper, Gillette Co, Boston, MA), lindane shampoo, methylene chloride, detergent, lidocaine, and hydrogen peroxide. More severe injection (at least grade 2) was seen in patients exposed to lindane, methylene chloride, detergent, potassium hydroxide, alkaline cleaner, and ammonium chloride. The others had mild injection. To show that the preference was not influenced by the order each solution was given, correlations were run between patient ranking and the order a solution was administered. Correlation coefficients were below .25 with each solution. Comments elicited could be grouped as negative: “buming,” “ stinging,” and “irritating,” and as positive: “cool,” Positive comments were offered for “OK,” “soothing.” NS, LR, NS + Bicarb, and BSS Plus, 25%, 41%, 50%, and 75% of the time, respectively. No patient had trouble distinguishing between positive and negative comments and gave

Constituents 120-135 mmol/L sodium chloride 26 mmol/L sodium bicarbonate 15-29 mmol/L potassium chloride 154 mmol/L 154 mmol/L .2 mmol/L 102 mmol/L 4 mmol/L 3 mmol/L 28 mmol/L 122 mmol/L 5 mmol/L 1 mmol/L 3 mmol/L 25 mmol/L 5 mmol/L .3 mmol/L

sodium chloride sodium chloride sodium bicarbonate sodium chloride potassium chloride calcium chloride sodium lactate sodium chloride potassium chloride calcium chloride disodium phosphate sodium bicarbonate dextrose glutathione (oxidized)

negative comments for NS, LR, NS + Bicarb, and BSS Plus, 75%, 5%, 50%, and 25% of the time, respectively. Exact ranking of each fluid is illustrated in Figure 1. Overall, rankings (f SD) for NS, LR, NS + Bicarb, and BSS Plus were, 3.17 (*.94), 2.63 (-el.ll), 2.54 (+1.17), and 1.67 (?.75), respectively. The differences among solutions were statistically significant, (x2 = 8.76, P < .05). BSS Plus was significantly preferred over NS (P < .Ol). Both LR and NS + Bicarb were intermediate in rankings; neither differed significantly from NS or BSS. A power analysis indicated a sample size of 29 patients is required to show that LR or NS + Bicarb is superior to NS by 1.0 in ranking (at the P < .05 significance level). Showing BSS superior to LR or NS + Bicarb (again specifying P < .05 difference of 1.O in ranking) would require a sample size of 13 and 34, respectively. In the discomfort category, discomfort (?SD) for NS, LR, NS + Bicarb, and BSS Plus was 4.9 (*3.4), 3.6 (?2.1), 3.5 (?2.6), and 2.0 (? 1.6), respectively. BSS Plus scored significantly better than NS (P< .Ol). Both LR and NS + Bicarb were intermediate in discomfort. Neither differed significantly from NS or BSS Plus. Power analysis indicated that a sample size of 117 is required to show a P < .05 superiority of 1.0 of LR or NS + Bicarb over NS. Showing BSS superior to LR or NS + Bicarb (again specifying P < .05 difference of 1.0 in discomfort) would require a sample size of 29 and 31, respectively. Irritation required that the infusion be stopped in three different patient trials: twice with normal saline, once with NS + Bicarb. In each case, other solutions were nearly as intolerable except for BSS Plus. No patient elected to withdraw from the study. Examination of pH and injection showed eventual normalization of conjunctival pH with each of the four irrigation fluids. There was no associated change in conjunctival injection with any particular solution. DISCUSSION Chemical spillage into the eye makes up 9.9% of ocular trauma in the United States’ and 7.2% in a British casualty

AMERICAN

230

I BSS

PLUS

I

I

NS

LR

TYPE

JOURNAL

NS +BICARB

OF FLU10

FIGURE 1. Number of rankings given each fluid (each circle rep-

resents one selection). Ties are recorded the average of rankings. department.’ Most are relatively innocuous substances such as shampoo and hairspray. Acid and base burns as a portion of eye injury were found only 1.6% and 0.6% of the time, respectively. ’ Occasionally, strong alkalis and acids are poured over lovers suspected of infidelity.3 While uncommon, chemical bums constitute true emergencies. The immediate management may be the single most important factor in determining the outcome.1’4m9 Injury begins with a corneal epithelial defect that can result in clouding of the cornea and conjunctiva. Alkali exposure has been found to penetrate the cornea and can alkalinize the aqueous humor within 1 to 10 minutes.‘j It can cause damage to the iris, ciliary body, lens, and trabecular meshwork resulting in glaucoma and loss of vision.1,6 Any suspicion that ocular exposure could involve a damaging chemical requires immediate, extensive irrigation of the eye.‘r4,5’.9-~’ One should initially use the most readily available source of water at the scene of the accident.‘,“*i2 For acid or base bums, one author recommends that irrigation be continued during transport to the medical facility.’ Medical treatment includes removal of any particulate matter from the conjunctiva and continuous irrigation until the pH in the conjunctival sac approximates 7.4. Recommendations of minimal irrigation time for acid and alkali bums ranges from 20 minutes’ to between 2 to 4 hours.’ Recommended fluids include water,4 NS,4,5y’o and LR.’ The ideal fluid would be effective at irrigation and pH normalization, comfortable at copious flow rates, and inexpensive. The search for a fluid better tolerated than NS included adjusting the mildly acidic pH of NS (pH 4.5-6.0) to better approximate the physiological pH of the conjunctiva (pH 7.4) by adding sodium bicarbonate. Because of instability of pH, this was done immediately before use in addition to vigorous shaking of the bottle. LR, which ranges from pH 6.0 to 7.2 depending on lot number, was selected as inexpensive, available, and less acidic than NS. BSS Plus was developed for ophthalmic operations that require prolonged irrigation after NS and LR solutions were found to damage comeal endothelium.i3,i4 It is similar to aqueous humor, containing bicarbonate, glucose, and

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n Volume 9, Number 3 n May 1991

glutathione. lJ It has been shown to prevent comeal swelling and preserve cornea1 endothelium.i6,” Major drawbacks include the need to reconstitute this solution from a 20 mL vial of concentrate and 480 mL of fluid, the need to discard unused solutions 6 hours after reconstitution,‘3 and cost in excess of $100 per 500 mL bottle. The preference for BSS Plus over NS may result from one or more properties: more physiological pH, osmolality, chemical constituents, or enhanced buffering capacity. Whereas its current expense and inconvenience precludes its routine use as an eye irrigant, BSS Plus appears to be a reasonable alternative for patients with poor tolerance to normal saline or who must undergo prolonged ocular inigation. Because three patients asked to have infusions of NS or NS + Bicarb stopped, it is possible that chemical damage to eye tissue could have resulted had no tolerable alternate solution been available. Direct benefit is difficult to calculate because in most cases improved comfort would yield no direct pay-off. However, in patients with acid or alkali bums who require that NS irrigation be turned down to a trickle or stopped, its use may be priceless to preserve vision. Its routine use during ocular surgery means it is probably already stocked in those hospitals offering ophthalmologic surgery and could be retrieved from storage when needed. NS + Bicarb was associated with a nonsignificant trend towards better tolerance. Exact titration to pH 7.4 was not possible, because of the impracticality of using a pH meter at the bedside. Bench titrations on three bottles from the same lot number used in the trial showed initial pHs of 5.95, 6.0, and 6.0. Because identical lot numbers were used clinically, it is likely that bicarbonate-adjusted pH was near 7.4 as well, although this could not be proven without having had a bedside pH meter. LR is inexpensive and available, yet is tolerated only slightly better than NS. Because power analysis showed a sample size of 117 is needed to show a discomfort difference of 1.0 at the P < .05 significance level, it is doubtful that it can be shown to offer additional benefit. It is unknown if a painful irrigation means that the cornea is being directly damaged. Further studies are needed to examine the effects on cornea1 swelling and epithelialization for external irrigation, as has been done for internal irrigation. Because this study is limited by the few patients with severe acid or alkali bums, a larger study is indicated to confirm these findings in those who most urgently need copious, uninterrupted eye irrigation. CONCLUSION We conclude that there are significant differences in preference and comfort among ocular irrigation fluids used following chemical injuries. Intolerance to the most widely recommended fluid, NS, caused the infusion to be stopped in two patients and NS was ranked lowest and had the most discomfort. LR and NS + Bicarb were intermediate in preference. BSS Plus was clearly preferred, and was the only solution significantly more comfortable than NS. Drawbacks include the need for reconstitution and high cost, which must be weighed against the benefit of achieving copious irrigation in a comfortable, cooperative patient. BSS Plus is probably already stocked in hospitals that host ophthalmologic sur-

HERR ET AL n COMPARISON OF OCULAR IRRIGATION FLUID

gery. Its use is most appropriately

considered for those patients whose poor tolerance to standard solutions threatens to delay or interrupt eye irrigation after chemical exposure. The authors wish to thank Alcon Laboratories for donating BSS Plus, William Rusho, RPh, for titrating normal saline with bicarbonate, James Reading, PhD, for inestimable statistical assistance, Ann Markowitz for securing pharmacy supplies, Patti Hogan, RN, for advice, and the nurses, interns, and medical students at University of Utah Emergency Room for their interest in and cooperation with this study.

REFERENCES 1. Pfister RR: Chemical cornea1 burns. In Olson RJ (ed): Common Cornea1 Problems. Boston, MA, Little, Brown, 1984, pp 157-l 88 2. Edwards RS: Ophthalmic emergencies in a district general hospital. Br J Ophthalmol 1987;71:938-942 3. Klein R, Lobes LA Jr: Ocular alkali burns in a large urban area. Ann Ophthalmol 1978;8:1185-1189 4. Parrish CM, Chandler JW: Cornea1 trauma. In Kaufman HE, Barron BA, McDonald MB, et al (eds): The Cornea. New York, NY, Churchill Livingstone, 1988, pp 808-821 5. Lubeck D, Greene JS, Cornea1 injuries. Emerg Med Clin North Am 1988;8:73-94 8. Grant WM, Kern HL: Action of alkalies on the cornea1 stroma. Arch Ophthalmol 1955;54:931-939

7. Hughes WF: Alkali burns of the eye I. Arch Ophthalmol 1948;35:423-449 8. Hughes WF: Alkali burns of the eye Il. Arch Ophthalmol 1948;38:189-214 9. Rodeheaver GT, Hiebert JM, Edlich RF: Initial treatment of chemical skin and eye burns. Compre Ther 1982;8:37-43 10. Cohen KL, Hyndiuk RA: Ocular emergencies. Am Fam Phys 1978;18:178-184 11. Preserving eyesight through quick response. Occup Health Saf 1981;50:70-71 12. Clark R: Ocularemergencies. In Tintinalli J, Krome R, Ruiz E (eds): Emergency Medicine: A Comprehensive Study Guide (ed 2). New York, NY, McGraw-Hill, 1988, p 582 13. Intraocular irrigation solutions. Monograph. Alcon Laboratories, Fort Worth, Texas, 1988 14. Edelhauser HF, Gonnering R, Van Horn DL: Intraocular irrigating solution, a comparative study of BSS Plus and lactated Ringer’s solution. Arch Ophthalmol 1978;98:518-520 15. McDermott ML, Edelhauser HF, Hack HM, et al: Ophthalmic irrigants: A current review and update. Ophthalmic Surg 1988;19:724-733 18. Edelhauser HF, MacRae SM: Irrigating and viscous solutions. In Sears M, Tarkkanen A: Surgical Pharmacology of the Eye. New York, NY, Raven Press, 1985, pp 363-387 17. McNamara MJ, Seaber AV, Urbaniak JR: Effect of irrigation fluids on arterial and venous endothelium after ischemia. J Reconstr Microsurg 1987;4:27-32

Clinical comparison of ocular irrigation fluids following chemical injury.

This study tested the hypothesis that four ocular irrigating solutions were equally irritating during copious irrigation. We conducted a prospective, ...
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