Comparative Study between the Efficacy of Fentanyl, Antihistamines, and Dexmedetomidine in Suppressing Photic Sneeze Reflex during Peribulbar Block

Abstract

Background:

The photic sneeze reflex (autosomal dominant) is a condition that causes sneezing in response to numerous stimuli, such as looking at bright lights or periocular (surrounding the eyeball) injection. Unexpected or sudden sneezing during injection can be a dangerous side effect in periocular injection, in which abrupt head movement may cause globe injury.

Aims:

We intended to evaluate the efficacy of adding fentanyl, dexmedetomidine, and antihistamines on the incidence of the sneeze reflex associated with propofol sedation during periocular local anesthesia injections.

Settings and Design:

Our study was a randomized, prospective, double-blinded and controlled clinical study.

Patients and Methods:

This study was conducted in Ain Shams and Fayoum university hospitals at the ophthalmic surgery department. After obtaining approval from our universities ethical committee and written informed valid consents from the patients, 90 patients were included in this study. The study population included patients of both sex, ASA grade 1 and 2, in the age ranging from 18-65 years. Patients were scheduled for cataract extraction surgeries and received peribulbar block. Then patients were randomly divided into three groups (30 patients each) using a computer- generated table of random numbers. Patients were preoxygenated with supplemental oxygen by nasal cannula, all 90 patients received intravenous propofol 1mg.kg- 1 bolus for sedation and were randomized to receive adjunctive drug 2 to 4 minutes prior to propofol injection: 30 patients received intravenous fentanyl 1 μmg.kg^-1 (Group F), 30 patients received dexmedetomidine 1μmg.kg^-1 (Group D), and 30 patients received antihistamine (pheniramine 22.75 mg) (Group H). The same local anesthetic admixture, consisting of 5 mL 2% lidocaine with 90 IU hyaluronidase, combined with 5 mL 0.5% plain bupivacaine in a 10-mL syringe at room temperature was administered to all patients using peribulbar block technique. A masked observer (surgeon or anesthesia assistant) recorded whether the patient had a sneezing event. Continuous cardiorespiratory monitoring was performed intraoperatively. Intraoperative and postoperative medication side effects were recorded including bradycardia (HR <55 beats/min), hypotension (MAP <50 mmHg sustained for >10 min), oxygen desaturation (SpO2<90%), nausea, vomiting and prolonged sedation using Ramsay Sedation Score (RSS).

Statistical Analysis Used:

Student's t-test and Chi-square test were used for analysis.

Results:

The demographic data of the three study groups revealed non-significant differences between the three study groups as regards age, sex distribution, and the duration of surgery. No patient was excluded after inclusion to the study. All patients were able to complete the entire study and their data were included in the final analysis. Five events of sneezing had occurred in 90 patients. Two in (D) group and three in (H) group with is no statistically significant difference between the three groups as regard sneezing. Bradycardia, hypotension and sedation had occurred significantly in group (D) compared to group (F) and group (D). No patient suffered from nausea, vomiting or oxygen desaturation in all studied groups. No statistically significant difference as regards patient satisfaction between the three studied groups.

Conclusion:

Fentanyl, dexmedetomidine and antihistamines with propofol sedation suppress photic sneeze reflex during peribulbar block.

INTRODUCTION

The photic sneeze reflex (autosomal dominant) is a condition that causes sneezing in response to numerous stimuli such as looking at bright lights or periocular (surrounding the eyeball) injection.[1] Sneezing or the sternutatory reflex is a primitive neuromuscular physiological response to irritation. The ophthalmic (VI) or maxillary divisions (VII) of the trigeminal nerve when stimulated activate the afferent pathway to relay in trigeminal nucleus and reticular formation and are then relayed to the pons and medulla. Efferent fibers are sent to facial nerves, spinal nerves, and the diaphragm.[2] Periocular local anesthetic injection has been shown to activate this reflex, which may lead to sneezing.[3] Unexpected or sudden sneezing during injection can be a dangerous side effect in periocular injection, in which abrupt head movement may cause globe injury, globe penetration, or vascular injury with subsequent hematoma. The optic nerve may be similarly at risk during retrobulbar injections.[4] Propofol is highly effective in achieving rapid sedation and hypnosis with a low side effect profile. The short duration of action and rapid awakening characteristics are preferable for ophthalmic or other types of short-duration surgeries. Despite many benefits, propofol sedation has been involved in producing the photic reflex induced by periocular injections of anesthetics.[5] The aim of this study was to evaluate the efficacy of adding fentanyl, dexmedetomidine, and antihistamines on the incidence of the sneeze reflex associated with propofol sedation during periocular local anesthesia injections.

PATIENTS AND METHODS

This study was conducted in Ain Shams and Fayoum University Hospitals at the Ophthalmic Surgery Department. After obtaining approval from our university's ethical committee and written informed valid consents from the patients, 90 patients were included in this study. The study population included patients of both sex, ASA physical status Classes 1 and 2, in the age ranging from 18 to 65 years. Patients were scheduled for cataract extraction surgeries and received peribulbar block. Our study was a randomized, prospective, double-blinded, and controlled study. Patients excluded from our study were those with bleeding disorders or on anticoagulants, local infection at the injection site, mentally retarded, patient refusal, and history of allergy to local anesthetics, propofol, fentanyl, or dexmedetomidine. Preoperative investigations were in the form of electrocardiography (ECG), chest X-ray, complete blood picture, and coagulation profile. Details of anesthesia technique and study protocol were explained to the patients at the preoperative visit. Intravenous line was inserted and basic monitors were applied (ECG, pulse oximetry, and noninvasive blood pressure). Then, patients were randomly divided into three groups (30 patients each) using a computer-generated table of random numbers. Patients were preoxygenated with supplemental oxygen by nasal cannula; all 90 patients received intravenous propofol 1 mg/kg bolus for sedation and were randomized to receive adjunctive drug 2–4 min before propofol injection: 30 patients received intravenous fentanyl 1 μg/kg (Group F), 30 patients received dexmedetomidine 1 μg/kg (Group D), and 30 patients received antihistamines (pheniramine 22.75 mg) (Group H).

The same local anesthetic admixture, consisting of 5 mL 2% lidocaine with 90 IU hyaluronidase, combined with 5 mL 0.5% plain bupivacaine in a 10 mL syringe at room temperature was administered to all patients using peribulbar block technique by the same anesthetist who is not involved in the study. Injections were done just after achieving propofol hypnosis, which was determined by both nonresponse to verbal commands and loss of the blink response to digital eyelash stimulation and was completed before a return to consciousness. To eliminate a potentially confounding photic sneeze reflex, overhead surgical lamps were turned off, and all injections were performed under ambient room light conditions.

A masked observer (surgeon or anesthesia assistant) recorded whether the patient had a sneezing event. Continuous cardiorespiratory monitoring was performed intraoperatively. Intraoperative and postoperative medication side effects were recorded including bradycardia (heart rate [HR] <55 beats/min), hypotension (mean arterial pressure <50 mmHg sustained for >10 min), oxygen desaturation (SpO₂ <90%), nausea, vomiting, and prolonged sedation using Ramsay Sedation Score:

1. Anxious, agitated, or restless

2. Cooperative, oriented, and tranquil

3. Responds to command

4. Asleep but has a brisk response to light glabellar tap or loud auditory stimulus.

The patients were interviewed for subjective assessments of the adequacy of anesthesia and overall satisfaction. Assessment of patient's satisfaction was done by asking the patient to answer the question, “How would you rate your experience during surgery?” using a 7-point Likert verbal rating scale. This assessment of patient's satisfaction was performed just before shifting to ward to minimize the effects of sedation on patient's judgment.

1. Extremely dissatisfied

2. Dissatisfied

3. Somewhat dissatisfied

4. Undecided

5. Somewhat satisfied

6. Satisfied

7. Extremely satisfied.

The primary outcome of this study was to evaluate the efficacy of adding fentanyl, dexmedetomidine, and antihistamines on the incidence of the sneeze reflex associated with propofol sedation during periocular local anesthesia injections. The secondary outcome was to compare hypotension, bradycardia, sedation, and patient satisfaction between the studied groups.

Statistical analysis

Data were analyzed using SPSS 21.0 for Windows (SPSS, Chicago, IL, USA). Analysis of variance was used to compare the three groups for quantitative parametric data with post hoc Tukey's test performed if there was a significant difference among the groups; (a) Kruskal–Wallis test was used for quantitative nonparametric data. Chi-square test was used for comparison of qualitative data. Continuous parametric data were presented as mean ± standard deviation nonparametric data as median (interquartile range), and categorical data were presented as number of patients. P < 0.05 was considered as statistically significant. Using PASS 11 for sample size calculation, it was calculated that group samples’ size of 30 patients per group will achieve 82% power to detect a difference between the group proportions of 20%. The test statistic used is the two-sized Z-test with pooled variance. The significance level of the test was targeted at 0.05. The significance level achieved by this design is 0.0488.

RESULTS

The demographic data of the three study groups were summarized in Table 1. Statistical analysis revealed nonsignificant differences between the three study groups as regards age, sex distribution, and the duration of surgery. No patient was excluded after inclusion to the study. All patients were able to complete the entire study, and their data were included in the final analysis. Five events of sneezing had occurred in 90 patients; two patients in Group D and three patients in Group H with no statistically significant difference between the three groups as regards sneezing [Table 2]. Bradycardia, hypotension, and sedation had occurred significantly in Group D compared to Group F and Group H [Table 2]. No patient suffered from nausea, vomiting or oxygen desaturation in all studied groups. There was no statistically significant difference as regards patient satisfaction between the three studied groups [Table 2].

Table 1.

Demographic data

	Group F Fentanyl group (n=30)	Group D Dexmedetomidine group (n=30)	Group H Antihistamine group (n=30)	P
Age (years)	50.57±10.6	48.6±13.99	49.23±14.35	0.726
Gender (male/female)	17/13	16/14	18/12	0.873
Duration of the procedure (min)	32.8±4.3	33.8±6.7	33.07±8.9	0.879

Data are presented as mean±SD or ratio of patients. P>0.05 is considered statistically nonsignificant. SD=Standard deviation

Table 2.

Variable data

	Group FFentanyl group (n=30)	Group D Dexmedetomidine group (n=30)	Group H nAntihistamine group (n=30)	P
Sneeze	0	2	3	0.227
Bradycardia	0	6†	0	0.002*
Hypotension	0	8†	0	<0.001*
Sedation	2 (2-2)	2 (2-3)†	2 (2-2)	<0.001*
Satisfaction	6 (6-7)	6 (6-7)	6 (6-7)	0.689

Data are presented as median (IQR) or number of patients. *P<0.05 is considered statistically significant between the 3 groups, ^†P<0.05 is considered statistically significant between Group D and Groups F and H. IQR=Interquartile range

DISCUSSION

Tao, in his study in 2009 about sneezing reflex associated with intravenous sedation and periocular anesthetic injection, raised an interesting point regarding the potential of opioids and other sedatives in suppressing sneezing reflex during ocular regional blocks and he required further studies to be able to better identify which particular intravenous sedatives require greater surveillance to enhance patient safety, as well as methods to suppress this reflex.[6] In the current study, we compared the efficacy of fentanyl, dexmedetomidine, and antihistamines on sneezing photic reflex with propofol sedation during peribulbar block, in addition to their effect on HR, mean arterial blood pressure, sedation, and patient satisfaction. The sneezing center consists of neurons in the trigeminal nucleus and adjacent reticular formation. The afferent nerve fiber signals from the anterior and the upper nose propagate via the anterior ethmoidal branch of the first division of the trigeminal nerve [the ophthalmic nerve (V1)] and those from the lower nose and the orbit propagate via the second division of the trigeminal nerve (the maxillary nerve). The afferent fibers relay in the pons and the medulla. The efferent pathways relay from the medulla through the facial nerves and spinal nerves to the intercostal muscles and diaphragm and from the medulla to the sphenopalatine ganglion. They are distributed to the nasal mucosal blood vessels and glands, causing secretions and nasal congestion, which, in turn, may stimulate further sneezing.[2] Histamine release can be caused by allergens that bind to immunoglobulin E-loaded mast cells in the nasal mucosa, which leads to sneezing.[7]

Ahn et al. reported vigorous sneezing happened in 5% of patients receiving periocular anesthetic injection under intravenous sedation. These authors reported that there was no sneezing incidence in another group of patients receiving periocular anesthetic injection without intravenous sedation and concluded that physicians must be aware of the unusual and potentially dangerous sneeze phenomenon when periocular anesthetic injections were delivered under intravenous sedation.[8] In our study, five events of sneezing had occurred in 90 patients; two patients in Group D and three patients in Group H while no single event of sneezing occurred in patients of Group F with no statistically significant difference between the three groups as regards sneezing. Temporary respiratory inhibition due to the action of fentanyl at the mu opioid receptors, which acts on central nervous system respiratory nuclei, may explain our results in Group F where no patient in this group had sneezed after the peribulbar block. An increased depth of sedation due to synergistic effect between opioids and propofol may also suppress the sneezing reflex.[9] Although adverse effects such as prolonged apnea or toxicity were not noted in this series of patients, temporary respiratory suppression was seen in 7.1% of patients, and monitoring for the potential dangers of these drugs is mandatory.[4] Dexmedetomidine is a highly selective alpha-2 (α₂) agonist that is more potent than clonidine. It has sedative, anxiolytic, and analgesic properties without respiratory depression.[10] Its actions are like those of benzodiazepines when used for premedication. Two patients only had sneezing in Group D. On the other hand, bradycardia, hypotension, and sedation had occurred significantly in this group compared to Group F and Group H. Antihistamines effectively exert the competitive antagonism of histamine for the histamine-1 (H1) receptors. Itching and sneezing are suppressed by an antihistaminic blockade of the H1 receptors on the nasal sensory nerves. Most H1 antihistamines have been found to inhibit sneezing and to lessen the increase in vascular permeability with therapeutic equivalence.[11] In concordance with our results, Morley et al. observed that propofol-based intravenous sedation, in combination with periocular local anesthetic injections, induced sneezing in approximately one-sixth of the patients. These authors further concluded that a history of photic sneezing, bilateral or upper eyelid infiltration, deep sedation, and concurrent administration of midazolam increased the risk whereas adjunctive opioid use reduced it.[12]

CONCLUSION

Fentanyl, dexmedetomidine, and antihistamines with propofol sedation suppress photic sneeze reflex during peribulbar block. The use of dexmedetomidine can cause significant bradycardia, hypotension, and sedation compared with the use of fentanyl and antihistamines.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.