- Email: [email protected]
Sneezing Reflex Associated with Intravenous Sedation and Periocular Anesthetic Injection
Sneezing Reflex Associated with Intravenous Sedation and Periocular Anesthetic Injection ERIC S. AHN, DAVID M. MILLS, DALE R. MEYER, AND GEORGE O. STASIOR ● PURPOSE:
To assess and compare the frequency of reflex sneezing occurring during periocular anesthetic injections with and without intravenous sedation. ● DESIGN: Retrospective, comparative case series. ● METHODS: Seven hundred and twenty-two patients undergoing oculoplastic surgical procedures were included in this study. Those who received a periocular anesthetic injection under intravenous sedation served as the test group of 381 subjects. Those who received a periocular anesthetic injection without intravenous sedation served as the control group of 341 subjects. The absence or presence of reflex sneezing in both groups was recorded and compared using Chi-square analysis. ● RESULTS: Of the 381 patients who received periocular anesthetic injections under intravenous sedation, 19 (5%) exhibited a vigorous sneeze. Conversely, none of the 341 patients who received periocular anesthetic injections without intravenous sedation sneezed (P < .001). ● CONCLUSIONS: Surgeons, anesthesia staff, and other operating room personnel should be aware of this unusual and potentially dangerous sneeze phenomenon when periocular anesthetic injections are delivered under intravenous sedation to reduce potential ocular complications. (Am J Ophthalmol 2008;146:31–35. © 2008 by Elsevier Inc. All rights reserved.)
I
NTRAVENOUS SEDATION IS USED IN MANY SURGICAL
procedures because it offers fairly rapid induction and recovery and can be used adjunctively with other forms of local anesthesia. Oculoplastic surgeons frequently rely on intravenous sedation while administering periocular anesthetic injections before surgery. The additional benefits of relaxation and suppression of sensorimotor afferents and efferents assist the surgeon in safely and comfortably administering local anesthesia to the highly innervated periocular area. Despite these benefits, however, care should be taken when delivering periocular anesthetic injections. A limited number of reports exist documenting reflex sneezing during preparation for certain ocular procedures.1,2
Accepted for publication Feb 15, 2008. From the Department of Ophthalmology at Albany Medical Center, Lions Eye Institute, Ophthalmic Plastic Surgery, Slingerlands, New York. Inquiries to Eric S. Ahn, Albany Medical Center, Lions Eye Institute, 1220 New Scotland Avenue, Suite 302, Slingerlands, NY 12159; e-mail: [email protected] 0002-9394/08/$34.00 doi:10.1016/j.ajo.2008.02.013
©
2008 BY
When performing oculoplastic surgical procedures, we also have noted the occurrence of vigorous reflex sneezing in patients receiving a periocular anesthetic injection under intravenous sedation in the operating room. This reflex was conspicuously absent when similar injections were performed in the office setting without intravenous sedation. This study was undertaken to assess the frequency of this phenomenon and its possible association with periocular injections delivered under intravenous sedation for oculoplastic surgical procedures. We specifically questioned whether it was the injection alone or in combination with intravenous sedation that led to the occurrence of a reflex sneeze. We attempted to delineate such a relationship to elaborate on a potential cause of injury, as well as to educate other physicians and operating room personnel involved with these types of procedures. In addition, we reviewed the literature to assess the current understanding and awareness of this phenomenon, including the possible physiologic features governing this reaction.
METHODS ALL PATIENTS UNDERGOING OCULOPLASTIC SURGICAL
procedures with either periocular anesthetic injection alone or in combination with intravenous sedation were included in this retrospective chart review over an 18month period from September 1, 2005 through March 31, 2007. Patients who received periocular anesthetic injections alone served as the control group, whereas those who received periocular anesthetic injections under intravenous sedation served as the test group. Patients given general anesthesia were excluded from the study, which secondarily eliminated most of the pediatric population because this age group typically received general anesthesia. Demographic information and procedural information were recorded for each patient who sneezed during a periocular anesthetic injection. Oculoplastic surgical procedures performed in this series included: incisional or excisional biopsies of benign and malignant eyelid and conjunctival lesions, primary wound repair, eyelid reconstruction of various types, eyelid malposition (ectropion and entropion) repairs, upper and lower eyelid functional and cosmetic blepharoplasties, limited anterior orbitotomies, tarsorrhaphies, chalazion incision and drainage procedures, trichiasis correction procedures includ-
ELSEVIER INC. ALL
RIGHTS RESERVED.
31
ing electrolysis, cryotherapy, and surgery, ptosis repair procedures including levator advancement, conjunctivoMüllerectomy, and frontalis sling, canthoplasties, symblepharon lysis procedures, conjunctivoplasties, dacryocystorhinostomies and conjunctivodacryocystorhinostomies with Jones tube placement, direct and endoscopic functional and cosmetic brow lifts, CO2 laser skin resurfacing procedures, eyelid retraction repair, and eyelid gold weight placements. During these procedures, patients were supine with the head of the table slightly elevated and overhead lights directed away from their eyes. If used, monitored anesthesia care with intravenous sedation then was administered, after which loss of sensation was confirmed by the absence of eyelash responsiveness. An infiltrative or regional periocular block consisting of 2% xylocaine with 1:100,000 epinephrine, typically buffered with 10:1 sodium bicarbonate, was applied afterward. The volume of anesthetic injection varied from 1 to 5 ml per site, with a maximum of 10 ml total for two lids. One of the oculoplastic surgeons (D.M.M.) directly monitored each patient during all procedures and documented the presence of reflex sneezing in a surgical log book. A sneeze was recorded only for those reactions that could be described as “involuntary, sudden, violent, and [an] audible expulsion of air through the mouth and nose.”3
represented right-side only procedures, six (31.6%) of 19 patients represented left-side only procedures, and eleven (57.9%) of 19 patients represented bilateral procedures. All 19 patients (100%) received propofol (Diprivan; AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA) as part of their intravenous sedation. Seventeen (89.5%) of 19 patients also received midazolam (Versed; Hoffmann-La Roche, Inc, Nutley, New Jersey, USA), three (15.8%) of 19 patients also received fentanyl (Baxter Healthcare Corp Anesthesia and Critical Care, New Providence, New Jersey, USA), and one (5.0%) of 19 patients also received diphenhydramine (Benadryl; Parke Davis Division of Pfizer Co, New York, New York, USA). No adverse events or complications resulted from the sneeze reflexes observed in this study.
DISCUSSION INTRAVENOUS SEDATION FREQUENTLY IS USED IN THE OP-
erating room to provide anesthesia for more comfortable administration of periocular anesthetic injections in oculoplastic surgical procedures. Unanticipated movement by the patient during a periocular anesthetic injection, like that observed with sneezing, may threaten the patient’s sight. The surgeon performing the injection and other operating room and anesthesia personnel involved with the case should be aware of this potential risk. Based on limited previous reports of this particular reaction during periocular anesthetic injections, and having witnessed this phenomenon ourselves, we examined the actual frequency of this reflex during periocular injections and its possible association with intravenous sedation. In this study, we found that 19 patients (5%) sneezed violently during the injection, and all 19 were from the group injected under intravenous sedation. None of the patients receiving periocular anesthetic injections alone sneezed. This phenomenon seemed to be related to the use of intravenous sedation and occurred frequently enough to merit attention, given the common use of periocular anesthetic injections under intravenous sedation. All patients observed to sneeze received propofol as a component of the intravenous sedation delivered before injection. Other studies also have demonstrated a relationship between intravenous sedation (particularly propofol) and a sneezing reaction.2,4 The use of intravenous sedation, specifically propofol, has been shown to induce excitatory events related to effects on ␥-aminobutyric acid (GABA) receptors throughout the central nervous system (CNS), and possible antagonist effects on glycine in the spinal cord. Initially, alterations produced by propofol manifest by increased cortical activity, indicated by electroencephalogram (EEG) desynchronization and temporary suppression of inhibitory neurons in the brainstem. Reports have indicated that seizures, opisthotonus, and involuntary
RESULTS SEVEN HUNDRED AND TWENTY-TWO PATIENTS UNDERGO-
ing oculoplastic surgical procedures were included in the study period from September 1, 2005 through March 31, 2007. Three hundred and eighty-one (52.8%) of these patients received periocular anesthetic injections while under intravenous sedation, and 341 (47.2 %) received periocular anesthetic injections alone. Reflex sneezing occurred in 19 (5.0%) of 381 patients who received a periocular anesthetic injection under intravenous sedation, whereas none of the patients given only periocular anesthetic injections sneezed. This difference was statistically significant (P ⬍ .001). All of the patients in this series were given infiltrative anesthetic injections, with a small minority also receiving supplemental regional nerve blocks. Sneezing was noted in both groups, but the number receiving supplemental block precluded meaningful separate statistical analysis. Generally, each patient would average more than one but fewer than six forceful sneezes. None of the patients who sneezed had to be converted to general anesthesia in this study. Also, sneezing never recurred during the planned procedure, even with repeat injections. The mean age of the 19 patients who sneezed was 69 years (range, 41 to 89 years; standard deviation, 12 years). Eleven (57.9%) of 19 patients who sneezed were male and eight (42.1%) of 19 were female. Two (10.5%) of 19 patients 32
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JULY 2008
movements are possible side effects of the use of propofol.5 After this brief initial period, the desired shift to a generalized low-frequency delta wave pattern, characteristic of deep sleep, is achieved for sedation and analgesia. We postulate that the sneeze reflex observed in this study and others may be part of a tonically suppressed neuronal arc that temporarily becomes disinhibited through the administration of intravenous sedation. The threshold for inducing involuntary movements may be reduced, whereas the sensitivity to stimulation is increased. The introduction of a periocular anesthetic injection causes stimulation of the ophthalmic branch of the trigeminal nerve (V1), the maxillary branch of the trigeminal nerve (V2), or both, leading to downstream reception and summation by trigeminal sensory nuclei, especially at the caudalis subnucleus of the spinal trigeminal tract, thought to be a relay center for nociceptive information. Neuronal interactions may be altered by intravenous sedation, possibly allowing nociceptive signals from a periocular anesthetic injection to be transmitted aberrantly to areas of the brainstem that effect a sneeze response. Interestingly, studies have proposed that such a sneezing center may exist in the medulla in close proximity to the interpolaris-caudalis portions of the spinal trigeminal tract and nucleus.6,7 Clearly, however, despite the ability of intravenous sedation to alter stimulation threshold, unidentified patient-specific factors, the initial or maintenance dose of anesthetic, the time from induction to injection, or a combination thereof may affect the actual response to the agent such that involuntary movements and related types of reactions occur at variable frequency. Not all patients receiving injection under sedation sneezed. In these patients, sedation may have been of sufficient strength to have suppressed directly sensory transmission, the sneeze center, respiratory neurons, or a combination thereof. Also, enough time may have passed between intravenous sedation and the periocular anesthetic injection that there was a decreased effect on inhibitory neurons, perhaps by physiologic adjustments by the CNS or by local decreases in sedative concentration. Other patients may have had different patterns of neuronal connectivity or simply did not receive enough stimulation to incite the reflex. The stimulatory effects elicited by the anesthetic injection itself also deserve mention. One may wonder whether sneezing observed after a periocular anesthetic injection actually may result from direct activation of the physiologic sternutatory reflex because of stimulation of the anterior ethmoidal nerve (V1) near the medial wall of the orbit or the maxillary nerve (V2) near the lower nose and orbit.6 Although it is possible that sneezing may have resulted from direct stimulation of these nerves, as demonstrated with direct ethmoidal nerve stimulation,6 the sneezing observed in this study occurred only when a periocular anesthetic injection was administered under intravenous sedation, and never with a periocular anesthetic injection alone, despite overlapping injection locaVOL. 146, NO. 1
tions between the groups. (e.g., medial canthal blocks were delivered to patients in each group. However, only the patients receiving them under intravenous sedation ever sneezed.) This suggests that direct activation alone is less likely to cause reflex sneezing and that the sneezing observed in this study required more than physical manipulation alone. The sneezes observed in this study also occurred with injections in other locations away from the medial canthus or nose. Although we did not administer any retrobulbar blocks under intravenous sedation, previous studies have suggested an increased incidence of sneezing in response to periocular anesthetic injections under intravenous sedation as compared with retrobulbar injections delivered under similar intravenous sedation for procedures on the globe (cataract extraction, PKP, trabeculectomy, iridotomy, pterygium excision, etc.).1 In a study by Wessels, where all participants received intravenous sedation, 23.8% who received periocular anesthetic injections and 4.5% who received retrobulbar injections demonstrated reflex sneezing.1 In the same study, there also seemed to be no reported difference with regard to gender in the incidence of reflex sneezing induced by a periocular anesthetic injection under intravenous sedation.1 Our study also showed a relatively similar proportion of male (58%) and female (42%) patients displaying the sneeze phenomenon (P ⫽ .474). This study does not unequivocally implicate propofol as the primer of reflex sneezing, because approximately 90% of patients also received midazolam. However, other studies exist that link propofol with sneezing after local anesthetic injection to the eye.2,4 Further investigation would be needed to confirm any direct or causal association. That said, we found no studies to date that suggest midazolam as inciting this reflex. Even accepting the possible association of reflex sneezing with propofol, it would be unreasonable to avoid this agent based on our study and information in the literature, given its many well-recognized benefits. Rather, we advise surgeons and other operating room personnel to be aware that there may be a greater risk of sneezing with injections performed under sedating agents such as propofol. There have also been attempts to implicate the photosternutatory reflex, or autosomal-dominant compelling heliotropic ophthalmic outburst (ACHOO) syndrome, with sneezing that seems to result from ocular manipulation. The photosternutatory reflex or ACHOO syndrome manifests as vigorous and insuppressible reflex sneezing outbursts on sudden exposure to bright light.2 This reflex has been characterized as occurring in a susceptible individual sensitized to a dark environment who is subjected to intense light (flash bulbs, fluorescent bulbs, and the sun) or on photic EEG stimulation.8,9 These particular sneezes are intense, multiple (two to three), and have a refractory period of approximately 24 hours. They also typically occur three seconds after light exposure and show variable
SNEEZING REFLEX
33
plastic surgical procedures. Also, the amount of intravenous sedation may have been variable because it depended on the anesthetist or anesthesiologist, who varied by location and day. The actual use of intravenous sedation was chosen by the surgeon based on the type of procedure and patient preference, and the type of intravenous sedation was chosen by the anesthesia staff. Neither was randomized, nor were the subjects age or gender matched. Although we cannot exclude some other covariable, this does not change the conclusion of the study that there is a clear association between sneezing and the combination of anesthetic injection and intravenous sedation, under the general conditions described. Finally, this study was retrospective in nature, and future prospective studies using a standardized time between the initiation of intravenous sedation to the administration of the periocular anesthetic injection, standardized doses of intravenous sedation and local anesthetic injection, and group matched parameters by procedure, periocular anesthetic injection location, and demarcated zones may be helpful in substantiating our findings. In summary, periocular anesthetic injections elicited vigorous and potentially dangerous reflex sneezing in 19 (5%) of 381 oculoplastic surgical patients when delivered under intravenous sedation, but did not elicit a similar reflex in any of the 341 patients who received periocular anesthetic injections without intravenous sedation during the same period (P ⬍ .001). This is a potentially high-risk situation, because the sneeze reflex generates enough force to propel the patient’s head toward the periocular injection needle. Awareness of this sneeze reflex phenomenon by operating room personnel may help to reduce potential morbidity. Because intravenous sedation is used commonly in many surgical fields, this topic may have relevance to fields outside of ophthalmology as well. However, because the vast majority of injections were around the eyes, we cannot elaborate on the frequency of this phenomenon with injections in other locations. Nevertheless, we hope to have drawn attention to the frequency of reflex sneezing for the safety of patients undergoing periocular anesthetic injections.
penetrance and degree of severity with a prevalence of 11% to 36%.9 one may wonder whether some of the sneezes observed in this study actually represented sneezes because of this photosternutatory reflex phenomenon (from operating room lights or other stimuli) or whether perhaps patients with a positive photosternutatory reflex history would be more susceptible to reflex sneezing with a periocular anesthetic injection. This study cannot rule out the photosternutatory reflex as a cause of the observed sneezing, because this was not a factor that was controlled for specifically. However in general, patients were exposed to a minimum of light before and at the time of injection, with the operating room lights directed away from the patient until the initiation of surgery. Furthermore, all observed sneezes occurred at the time of the periocular anesthetic injection, and no patients sneezed during surgery when the lights were focused directly on them during the course of surgery. A study by Wessels specifically examined the photosternutatory reflex as a risk for sneezing with periocular anesthetic injections under intravenous sedation and demonstrated no statistical relationship (7.7% of patients with a history of photosternutatory reflex sneezed in response to periocular or retrobulbar injection vs 4.8% without a history of photosternutatory reflex who sneezed; P ⫽ .43).1 We did not specifically inquire as to whether our patients had a history of a photosternutatory reflex. Other potential limitations of our study also warrant mention. One may question the time that elapsed between the initiation of intravenous sedation to the administration of the periocular injection. It is possible that performing the periocular injections at various times after intravenous sedation may alter the frequency of the sneezing reflex. Although no specific interval was strictly adhered to before administering periocular anesthetic injections after intravenous sedation, it was common practice to proceed with the periocular anesthetic injection after the patient was found to be unresponsive to voice and touch using the eyelash reflex. Another potential area of variability was the amount of local anesthetic injected, because this study involved three surgeons who each delivered a preferred amount of anesthetic for oculo-
THE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FINANCIAL CONFLICT OF INTEREST. INVOLVED IN DESIGN AND conduct of study (E.S.A., D.M.M., D.R.M.); collection, management analysis, and interpretation of data (E.S.A., D.M.M., D.R.M., G.O.S.); and preparation, review, and approval of manuscript (E.S.A., D.M.M., D.R.M., G.O.S.). The Albany Medical College Institutional Review Board (IRB) considered this study exempt under local institutional review board guidelines. Health Insurance Portability and Accountability Act compliance was maintained. Care of the patients in this study was in adherence to the Declaration of Helsinki and all federal and state laws.
3. Dorland WAN. Dorland’s illustrated medical dictionary. Philadelphia, Pennsylvania: W.B. Saunders Co, 1994:1536. 4. Boezaart AP. A comparison of propofol and remifentanil for sedation and limitation of movement during periretrobulbar block. J Clin Anesth 2001;13:422– 426. 5. Sneyd JR. Excitatory events associated with propofol anesthesia: a review. J R Soc Med 1992;85:288 –291.
REFERENCES 1. Wessels IF. The photic sneeze reflex and ocular anesthesia. Ophthalmic Surg Lasers 1999;30:208 –211. 2. Abramson DC. Sudden unexpected sneezing during the insertion of peribulbar block under propofol sedation. Can J Anaesth 1995;42:740 –743.
34
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JULY 2008
6. Batsel HL, Lines AJ. Neural mechanisms of sneeze. Am J Physiol 1975;229:770 –776. 7. Martinez MS, Varela-Freijanes A, Grandes J, Vazquez F. Sneeze related area in the medulla: localisation of the human sneezing centre? J Neurol Neurosurg Psychiatry 2006;77:559 – 561.
8. Yarrow S. General anaesthesia and the photosternutatory reflex. Anaesthesia 2003;58:925–926. 9. Moreno JMG, Paramo MC, Navarro G, Gamero M, Lucas M, Izquierdo G. Autosomal dominant compelling helio-ophthalmic outburst syndrome (photic sneeze reflex): clinical study of six Spanish families. Neurologia 2005;20:276 –282.
AJO History of Ophthalmology Series George Milbry Gould, the Refractionist
G
eorge Milbry Gould (1848 to 1922) was a Philadelphia ophthalmologist with an international reputation, recognized as a medical editor of great distinction and author of the famous Gould Medical Dictionary. His whole life in ophthalmology was dominated by his crusade for careful cycloplegic refractions. Like most refractionists, he believed that a suitable pair of glasses not only sharpened the vision, but sometimes rested straining eyes. To him, this relief was of crucial importance because he felt that the unconscious effort of straining for clear vision would, if not corrected, so drain and weaken the body, the mind, and the will as to make a person
VOL. 146, NO. 1
vulnerable to many diseases, including especially migraine headaches, myopia, macular degeneration, insomnia, night terrors, depression, vertigo, epilepsy, and all manner of digestive troubles leading to anorexia and malnutrition and hence to anemia and so to various infections. At his office he was a charismatic refractionist who, every afternoon, went happily to work convinced that he was not only improving his patients’ eyesight but also their general health. Provided by H. Stanley Thompson, MD, of the Cogan Ophthalmic History Society.
SNEEZING REFLEX
35
To assess and compare the frequency of reflex sneezing occurring during periocular anesthetic injections with and without intravenous sedation. ● DESIGN: Retrospective, comparative case series. ● METHODS: Seven hundred and twenty-two patients undergoing oculoplastic surgical procedures were included in this study. Those who received a periocular anesthetic injection under intravenous sedation served as the test group of 381 subjects. Those who received a periocular anesthetic injection without intravenous sedation served as the control group of 341 subjects. The absence or presence of reflex sneezing in both groups was recorded and compared using Chi-square analysis. ● RESULTS: Of the 381 patients who received periocular anesthetic injections under intravenous sedation, 19 (5%) exhibited a vigorous sneeze. Conversely, none of the 341 patients who received periocular anesthetic injections without intravenous sedation sneezed (P < .001). ● CONCLUSIONS: Surgeons, anesthesia staff, and other operating room personnel should be aware of this unusual and potentially dangerous sneeze phenomenon when periocular anesthetic injections are delivered under intravenous sedation to reduce potential ocular complications. (Am J Ophthalmol 2008;146:31–35. © 2008 by Elsevier Inc. All rights reserved.)
I
NTRAVENOUS SEDATION IS USED IN MANY SURGICAL
procedures because it offers fairly rapid induction and recovery and can be used adjunctively with other forms of local anesthesia. Oculoplastic surgeons frequently rely on intravenous sedation while administering periocular anesthetic injections before surgery. The additional benefits of relaxation and suppression of sensorimotor afferents and efferents assist the surgeon in safely and comfortably administering local anesthesia to the highly innervated periocular area. Despite these benefits, however, care should be taken when delivering periocular anesthetic injections. A limited number of reports exist documenting reflex sneezing during preparation for certain ocular procedures.1,2
Accepted for publication Feb 15, 2008. From the Department of Ophthalmology at Albany Medical Center, Lions Eye Institute, Ophthalmic Plastic Surgery, Slingerlands, New York. Inquiries to Eric S. Ahn, Albany Medical Center, Lions Eye Institute, 1220 New Scotland Avenue, Suite 302, Slingerlands, NY 12159; e-mail: [email protected] 0002-9394/08/$34.00 doi:10.1016/j.ajo.2008.02.013
©
2008 BY
When performing oculoplastic surgical procedures, we also have noted the occurrence of vigorous reflex sneezing in patients receiving a periocular anesthetic injection under intravenous sedation in the operating room. This reflex was conspicuously absent when similar injections were performed in the office setting without intravenous sedation. This study was undertaken to assess the frequency of this phenomenon and its possible association with periocular injections delivered under intravenous sedation for oculoplastic surgical procedures. We specifically questioned whether it was the injection alone or in combination with intravenous sedation that led to the occurrence of a reflex sneeze. We attempted to delineate such a relationship to elaborate on a potential cause of injury, as well as to educate other physicians and operating room personnel involved with these types of procedures. In addition, we reviewed the literature to assess the current understanding and awareness of this phenomenon, including the possible physiologic features governing this reaction.
METHODS ALL PATIENTS UNDERGOING OCULOPLASTIC SURGICAL
procedures with either periocular anesthetic injection alone or in combination with intravenous sedation were included in this retrospective chart review over an 18month period from September 1, 2005 through March 31, 2007. Patients who received periocular anesthetic injections alone served as the control group, whereas those who received periocular anesthetic injections under intravenous sedation served as the test group. Patients given general anesthesia were excluded from the study, which secondarily eliminated most of the pediatric population because this age group typically received general anesthesia. Demographic information and procedural information were recorded for each patient who sneezed during a periocular anesthetic injection. Oculoplastic surgical procedures performed in this series included: incisional or excisional biopsies of benign and malignant eyelid and conjunctival lesions, primary wound repair, eyelid reconstruction of various types, eyelid malposition (ectropion and entropion) repairs, upper and lower eyelid functional and cosmetic blepharoplasties, limited anterior orbitotomies, tarsorrhaphies, chalazion incision and drainage procedures, trichiasis correction procedures includ-
ELSEVIER INC. ALL
RIGHTS RESERVED.
31
ing electrolysis, cryotherapy, and surgery, ptosis repair procedures including levator advancement, conjunctivoMüllerectomy, and frontalis sling, canthoplasties, symblepharon lysis procedures, conjunctivoplasties, dacryocystorhinostomies and conjunctivodacryocystorhinostomies with Jones tube placement, direct and endoscopic functional and cosmetic brow lifts, CO2 laser skin resurfacing procedures, eyelid retraction repair, and eyelid gold weight placements. During these procedures, patients were supine with the head of the table slightly elevated and overhead lights directed away from their eyes. If used, monitored anesthesia care with intravenous sedation then was administered, after which loss of sensation was confirmed by the absence of eyelash responsiveness. An infiltrative or regional periocular block consisting of 2% xylocaine with 1:100,000 epinephrine, typically buffered with 10:1 sodium bicarbonate, was applied afterward. The volume of anesthetic injection varied from 1 to 5 ml per site, with a maximum of 10 ml total for two lids. One of the oculoplastic surgeons (D.M.M.) directly monitored each patient during all procedures and documented the presence of reflex sneezing in a surgical log book. A sneeze was recorded only for those reactions that could be described as “involuntary, sudden, violent, and [an] audible expulsion of air through the mouth and nose.”3
represented right-side only procedures, six (31.6%) of 19 patients represented left-side only procedures, and eleven (57.9%) of 19 patients represented bilateral procedures. All 19 patients (100%) received propofol (Diprivan; AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA) as part of their intravenous sedation. Seventeen (89.5%) of 19 patients also received midazolam (Versed; Hoffmann-La Roche, Inc, Nutley, New Jersey, USA), three (15.8%) of 19 patients also received fentanyl (Baxter Healthcare Corp Anesthesia and Critical Care, New Providence, New Jersey, USA), and one (5.0%) of 19 patients also received diphenhydramine (Benadryl; Parke Davis Division of Pfizer Co, New York, New York, USA). No adverse events or complications resulted from the sneeze reflexes observed in this study.
DISCUSSION INTRAVENOUS SEDATION FREQUENTLY IS USED IN THE OP-
erating room to provide anesthesia for more comfortable administration of periocular anesthetic injections in oculoplastic surgical procedures. Unanticipated movement by the patient during a periocular anesthetic injection, like that observed with sneezing, may threaten the patient’s sight. The surgeon performing the injection and other operating room and anesthesia personnel involved with the case should be aware of this potential risk. Based on limited previous reports of this particular reaction during periocular anesthetic injections, and having witnessed this phenomenon ourselves, we examined the actual frequency of this reflex during periocular injections and its possible association with intravenous sedation. In this study, we found that 19 patients (5%) sneezed violently during the injection, and all 19 were from the group injected under intravenous sedation. None of the patients receiving periocular anesthetic injections alone sneezed. This phenomenon seemed to be related to the use of intravenous sedation and occurred frequently enough to merit attention, given the common use of periocular anesthetic injections under intravenous sedation. All patients observed to sneeze received propofol as a component of the intravenous sedation delivered before injection. Other studies also have demonstrated a relationship between intravenous sedation (particularly propofol) and a sneezing reaction.2,4 The use of intravenous sedation, specifically propofol, has been shown to induce excitatory events related to effects on ␥-aminobutyric acid (GABA) receptors throughout the central nervous system (CNS), and possible antagonist effects on glycine in the spinal cord. Initially, alterations produced by propofol manifest by increased cortical activity, indicated by electroencephalogram (EEG) desynchronization and temporary suppression of inhibitory neurons in the brainstem. Reports have indicated that seizures, opisthotonus, and involuntary
RESULTS SEVEN HUNDRED AND TWENTY-TWO PATIENTS UNDERGO-
ing oculoplastic surgical procedures were included in the study period from September 1, 2005 through March 31, 2007. Three hundred and eighty-one (52.8%) of these patients received periocular anesthetic injections while under intravenous sedation, and 341 (47.2 %) received periocular anesthetic injections alone. Reflex sneezing occurred in 19 (5.0%) of 381 patients who received a periocular anesthetic injection under intravenous sedation, whereas none of the patients given only periocular anesthetic injections sneezed. This difference was statistically significant (P ⬍ .001). All of the patients in this series were given infiltrative anesthetic injections, with a small minority also receiving supplemental regional nerve blocks. Sneezing was noted in both groups, but the number receiving supplemental block precluded meaningful separate statistical analysis. Generally, each patient would average more than one but fewer than six forceful sneezes. None of the patients who sneezed had to be converted to general anesthesia in this study. Also, sneezing never recurred during the planned procedure, even with repeat injections. The mean age of the 19 patients who sneezed was 69 years (range, 41 to 89 years; standard deviation, 12 years). Eleven (57.9%) of 19 patients who sneezed were male and eight (42.1%) of 19 were female. Two (10.5%) of 19 patients 32
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JULY 2008
movements are possible side effects of the use of propofol.5 After this brief initial period, the desired shift to a generalized low-frequency delta wave pattern, characteristic of deep sleep, is achieved for sedation and analgesia. We postulate that the sneeze reflex observed in this study and others may be part of a tonically suppressed neuronal arc that temporarily becomes disinhibited through the administration of intravenous sedation. The threshold for inducing involuntary movements may be reduced, whereas the sensitivity to stimulation is increased. The introduction of a periocular anesthetic injection causes stimulation of the ophthalmic branch of the trigeminal nerve (V1), the maxillary branch of the trigeminal nerve (V2), or both, leading to downstream reception and summation by trigeminal sensory nuclei, especially at the caudalis subnucleus of the spinal trigeminal tract, thought to be a relay center for nociceptive information. Neuronal interactions may be altered by intravenous sedation, possibly allowing nociceptive signals from a periocular anesthetic injection to be transmitted aberrantly to areas of the brainstem that effect a sneeze response. Interestingly, studies have proposed that such a sneezing center may exist in the medulla in close proximity to the interpolaris-caudalis portions of the spinal trigeminal tract and nucleus.6,7 Clearly, however, despite the ability of intravenous sedation to alter stimulation threshold, unidentified patient-specific factors, the initial or maintenance dose of anesthetic, the time from induction to injection, or a combination thereof may affect the actual response to the agent such that involuntary movements and related types of reactions occur at variable frequency. Not all patients receiving injection under sedation sneezed. In these patients, sedation may have been of sufficient strength to have suppressed directly sensory transmission, the sneeze center, respiratory neurons, or a combination thereof. Also, enough time may have passed between intravenous sedation and the periocular anesthetic injection that there was a decreased effect on inhibitory neurons, perhaps by physiologic adjustments by the CNS or by local decreases in sedative concentration. Other patients may have had different patterns of neuronal connectivity or simply did not receive enough stimulation to incite the reflex. The stimulatory effects elicited by the anesthetic injection itself also deserve mention. One may wonder whether sneezing observed after a periocular anesthetic injection actually may result from direct activation of the physiologic sternutatory reflex because of stimulation of the anterior ethmoidal nerve (V1) near the medial wall of the orbit or the maxillary nerve (V2) near the lower nose and orbit.6 Although it is possible that sneezing may have resulted from direct stimulation of these nerves, as demonstrated with direct ethmoidal nerve stimulation,6 the sneezing observed in this study occurred only when a periocular anesthetic injection was administered under intravenous sedation, and never with a periocular anesthetic injection alone, despite overlapping injection locaVOL. 146, NO. 1
tions between the groups. (e.g., medial canthal blocks were delivered to patients in each group. However, only the patients receiving them under intravenous sedation ever sneezed.) This suggests that direct activation alone is less likely to cause reflex sneezing and that the sneezing observed in this study required more than physical manipulation alone. The sneezes observed in this study also occurred with injections in other locations away from the medial canthus or nose. Although we did not administer any retrobulbar blocks under intravenous sedation, previous studies have suggested an increased incidence of sneezing in response to periocular anesthetic injections under intravenous sedation as compared with retrobulbar injections delivered under similar intravenous sedation for procedures on the globe (cataract extraction, PKP, trabeculectomy, iridotomy, pterygium excision, etc.).1 In a study by Wessels, where all participants received intravenous sedation, 23.8% who received periocular anesthetic injections and 4.5% who received retrobulbar injections demonstrated reflex sneezing.1 In the same study, there also seemed to be no reported difference with regard to gender in the incidence of reflex sneezing induced by a periocular anesthetic injection under intravenous sedation.1 Our study also showed a relatively similar proportion of male (58%) and female (42%) patients displaying the sneeze phenomenon (P ⫽ .474). This study does not unequivocally implicate propofol as the primer of reflex sneezing, because approximately 90% of patients also received midazolam. However, other studies exist that link propofol with sneezing after local anesthetic injection to the eye.2,4 Further investigation would be needed to confirm any direct or causal association. That said, we found no studies to date that suggest midazolam as inciting this reflex. Even accepting the possible association of reflex sneezing with propofol, it would be unreasonable to avoid this agent based on our study and information in the literature, given its many well-recognized benefits. Rather, we advise surgeons and other operating room personnel to be aware that there may be a greater risk of sneezing with injections performed under sedating agents such as propofol. There have also been attempts to implicate the photosternutatory reflex, or autosomal-dominant compelling heliotropic ophthalmic outburst (ACHOO) syndrome, with sneezing that seems to result from ocular manipulation. The photosternutatory reflex or ACHOO syndrome manifests as vigorous and insuppressible reflex sneezing outbursts on sudden exposure to bright light.2 This reflex has been characterized as occurring in a susceptible individual sensitized to a dark environment who is subjected to intense light (flash bulbs, fluorescent bulbs, and the sun) or on photic EEG stimulation.8,9 These particular sneezes are intense, multiple (two to three), and have a refractory period of approximately 24 hours. They also typically occur three seconds after light exposure and show variable
SNEEZING REFLEX
33
plastic surgical procedures. Also, the amount of intravenous sedation may have been variable because it depended on the anesthetist or anesthesiologist, who varied by location and day. The actual use of intravenous sedation was chosen by the surgeon based on the type of procedure and patient preference, and the type of intravenous sedation was chosen by the anesthesia staff. Neither was randomized, nor were the subjects age or gender matched. Although we cannot exclude some other covariable, this does not change the conclusion of the study that there is a clear association between sneezing and the combination of anesthetic injection and intravenous sedation, under the general conditions described. Finally, this study was retrospective in nature, and future prospective studies using a standardized time between the initiation of intravenous sedation to the administration of the periocular anesthetic injection, standardized doses of intravenous sedation and local anesthetic injection, and group matched parameters by procedure, periocular anesthetic injection location, and demarcated zones may be helpful in substantiating our findings. In summary, periocular anesthetic injections elicited vigorous and potentially dangerous reflex sneezing in 19 (5%) of 381 oculoplastic surgical patients when delivered under intravenous sedation, but did not elicit a similar reflex in any of the 341 patients who received periocular anesthetic injections without intravenous sedation during the same period (P ⬍ .001). This is a potentially high-risk situation, because the sneeze reflex generates enough force to propel the patient’s head toward the periocular injection needle. Awareness of this sneeze reflex phenomenon by operating room personnel may help to reduce potential morbidity. Because intravenous sedation is used commonly in many surgical fields, this topic may have relevance to fields outside of ophthalmology as well. However, because the vast majority of injections were around the eyes, we cannot elaborate on the frequency of this phenomenon with injections in other locations. Nevertheless, we hope to have drawn attention to the frequency of reflex sneezing for the safety of patients undergoing periocular anesthetic injections.
penetrance and degree of severity with a prevalence of 11% to 36%.9 one may wonder whether some of the sneezes observed in this study actually represented sneezes because of this photosternutatory reflex phenomenon (from operating room lights or other stimuli) or whether perhaps patients with a positive photosternutatory reflex history would be more susceptible to reflex sneezing with a periocular anesthetic injection. This study cannot rule out the photosternutatory reflex as a cause of the observed sneezing, because this was not a factor that was controlled for specifically. However in general, patients were exposed to a minimum of light before and at the time of injection, with the operating room lights directed away from the patient until the initiation of surgery. Furthermore, all observed sneezes occurred at the time of the periocular anesthetic injection, and no patients sneezed during surgery when the lights were focused directly on them during the course of surgery. A study by Wessels specifically examined the photosternutatory reflex as a risk for sneezing with periocular anesthetic injections under intravenous sedation and demonstrated no statistical relationship (7.7% of patients with a history of photosternutatory reflex sneezed in response to periocular or retrobulbar injection vs 4.8% without a history of photosternutatory reflex who sneezed; P ⫽ .43).1 We did not specifically inquire as to whether our patients had a history of a photosternutatory reflex. Other potential limitations of our study also warrant mention. One may question the time that elapsed between the initiation of intravenous sedation to the administration of the periocular injection. It is possible that performing the periocular injections at various times after intravenous sedation may alter the frequency of the sneezing reflex. Although no specific interval was strictly adhered to before administering periocular anesthetic injections after intravenous sedation, it was common practice to proceed with the periocular anesthetic injection after the patient was found to be unresponsive to voice and touch using the eyelash reflex. Another potential area of variability was the amount of local anesthetic injected, because this study involved three surgeons who each delivered a preferred amount of anesthetic for oculo-
THE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FINANCIAL CONFLICT OF INTEREST. INVOLVED IN DESIGN AND conduct of study (E.S.A., D.M.M., D.R.M.); collection, management analysis, and interpretation of data (E.S.A., D.M.M., D.R.M., G.O.S.); and preparation, review, and approval of manuscript (E.S.A., D.M.M., D.R.M., G.O.S.). The Albany Medical College Institutional Review Board (IRB) considered this study exempt under local institutional review board guidelines. Health Insurance Portability and Accountability Act compliance was maintained. Care of the patients in this study was in adherence to the Declaration of Helsinki and all federal and state laws.
3. Dorland WAN. Dorland’s illustrated medical dictionary. Philadelphia, Pennsylvania: W.B. Saunders Co, 1994:1536. 4. Boezaart AP. A comparison of propofol and remifentanil for sedation and limitation of movement during periretrobulbar block. J Clin Anesth 2001;13:422– 426. 5. Sneyd JR. Excitatory events associated with propofol anesthesia: a review. J R Soc Med 1992;85:288 –291.
REFERENCES 1. Wessels IF. The photic sneeze reflex and ocular anesthesia. Ophthalmic Surg Lasers 1999;30:208 –211. 2. Abramson DC. Sudden unexpected sneezing during the insertion of peribulbar block under propofol sedation. Can J Anaesth 1995;42:740 –743.
34
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JULY 2008
6. Batsel HL, Lines AJ. Neural mechanisms of sneeze. Am J Physiol 1975;229:770 –776. 7. Martinez MS, Varela-Freijanes A, Grandes J, Vazquez F. Sneeze related area in the medulla: localisation of the human sneezing centre? J Neurol Neurosurg Psychiatry 2006;77:559 – 561.
8. Yarrow S. General anaesthesia and the photosternutatory reflex. Anaesthesia 2003;58:925–926. 9. Moreno JMG, Paramo MC, Navarro G, Gamero M, Lucas M, Izquierdo G. Autosomal dominant compelling helio-ophthalmic outburst syndrome (photic sneeze reflex): clinical study of six Spanish families. Neurologia 2005;20:276 –282.
AJO History of Ophthalmology Series George Milbry Gould, the Refractionist
G
eorge Milbry Gould (1848 to 1922) was a Philadelphia ophthalmologist with an international reputation, recognized as a medical editor of great distinction and author of the famous Gould Medical Dictionary. His whole life in ophthalmology was dominated by his crusade for careful cycloplegic refractions. Like most refractionists, he believed that a suitable pair of glasses not only sharpened the vision, but sometimes rested straining eyes. To him, this relief was of crucial importance because he felt that the unconscious effort of straining for clear vision would, if not corrected, so drain and weaken the body, the mind, and the will as to make a person
VOL. 146, NO. 1
vulnerable to many diseases, including especially migraine headaches, myopia, macular degeneration, insomnia, night terrors, depression, vertigo, epilepsy, and all manner of digestive troubles leading to anorexia and malnutrition and hence to anemia and so to various infections. At his office he was a charismatic refractionist who, every afternoon, went happily to work convinced that he was not only improving his patients’ eyesight but also their general health. Provided by H. Stanley Thompson, MD, of the Cogan Ophthalmic History Society.
SNEEZING REFLEX
35