From 1992 through 2013, patients undergoing strabismus or orbital surgery had deliberate, quantified extraocular muscle tension with prospective monitoring of electrocardiograph and anesthetic variables in an ongoing, HIPAA-compliant study with institutional review board approval from Providence Hospital (ClincalTrials.gov NCT03663413). This ongoing observational study complies with the Declaration of Helsinki and utilizes de-identified data; written informed consent has not been a requirement of the study. The intent of the study has been to monitor the oculocardiac reflex in community surgery centers with choice of agents up to the anesthesia teams. Since profound OCR is a relatively rare event, our ongoing prospective study using identical extraocular muscle stimulation provides a unique opportunity to observe large numbers of patients over time. This present report covers prospectively recorded anesthetic parameters in two cohorts representing different surgery centers and brain wave monitors, but identical strabismus rectus muscle stimulation to elicit oculocardiac reflex (Fig. 1). Patients were selected from all consecutive strabismus surgery patients of one surgeon (RWA) including ASA 1 and 2 patients some with developmental disabilities. There was no health or age related bias directing patients to either surgery center, however younger patients were more likely to receive pre-operative sedation- that may serve as a confounder with respect to age. Anesthesia staff was equally likely to increase or decrease anesthesia depth over the course off the surgery. The known confounder dexmedetomidine was not used in this study group [13]. Excluded were any patients given anticholinergic medication before OCR was measured and re-operations.
At the choice of the outpatient anesthesia team, some patients were given premedication: oral midazolam 0.5 mg/Kg. During induction, some patients were given IV fentanyl 1–2 mcg//Kg and/or propofol 3 mg/Kg. The children were induced with inhaled N2O and sevoflurane and then intravenous catheter inserted. No pre-operative, or induction anticholinergic was given. Most patients had laryngeal mask airway however some had general enotracheal. Few required rocuronium 0.5 mg/Kg. The anesthesiologist deliberately varied anesthetic agents, and specifically the inhalational agent concentration within customary levels to allow observation of the impact of lighter and deeper levels of anesthesia on the same patient.
From 2009 through 2013, each patient was monitored for electrocardiograph, end-tidal agent and CO2 concentration, and brain wave. Anesthetic depth was estimated using bispectral index (BIS) monitors (BIS XP, Aspect Medical Systems, Newton, Mass) in one center, and Narcotrend monitors (MonitorTechnik, Bad Bramstedt, Germany) in another surgical center. The monitors were applied to the forehead and temple according to manufacturer’s instructions, and covered with adhesive, transluscent plastic drape after iodophore preparation. Additional monitoring included end-tidal agent concentration, CO2 monitoring and electrocardiograph. Oculocardiac reflex (OCR) was monitored during deliberate, 10-s, square wave tension on carefully isolated extraocular rectus muscles. Some cases involved surgery on just one extraocular muscle, while the majority of cases involved surgery on more than one muscle with time for heart rate to return to stable baseline between deliberate tension.
Oculocardiac reflex is reported as the maximum percent change in heart rate from stable, pre-tension ECG to the maximally different heart rate induced by the 10-s, deliberate extraocular muscle tension. Stability in brain wave monitor also preceded OCR monitoring. Although some define OCR as a 20% drop in heart rate [17], percent change better allows for comparison between children and adults with different resting heart rates. A negative percent represents bradycardia ((OCR heart rate – pre-heart rate)/pre-heart rate), whereas a positive percent oculocaridac could represent tachycardia. By this definition, more OCR (greater minus percent) implies more bradycardia and lower heart rate. We differentiated between oculocardiac with gradual onset from those with rapid onset- defined by at least 25% heart rate change in the first two seconds after extraocular muscle tension. For practical approach reasons, for uniformity, and because it produces the greatest OCR of the recti [18], inferior rectus muscles were most commonly tested. An example of rapid-onset, inferior rectus oculocardiac reflex can be observed at https://vimeo.com/robertarnold/oculocardiacreflex.
Statistical methods
Continuous data %OCR and brain wave monitor readings were analyzed with linear regression with calculations for coefficient of regression with 95% confidence intervals and Pearson product moment correlation with p values before and after adjustment for multiple comparisons. For cases with two muscles recorded of a given patient, the difference in %OCR from muscle 1 to muscle 2 was correlated to the difference in brain wave monitor reading at time of deliberate muscle tension. Linear regression was also employed comparing %OCR to age.
A multi-variable analysis then sought contributing related explanatory variables as might influence depth of anesthesia (midazolam, propofol, opioid, nitrous oxide, inhalational agent concentration). A p value less than 0.05 was considered significant. To address interaction, interaction terms were generated between pairs of explanatory variables with or without Robust standard errors and none of these contributed to additional significance.
A student’s t-Test was employed to determine difference in means of cases showing rapid versus gradual onset OCR.
Sample size
For a correlation to detect an r of 0.3 or − 0.3 given power of 0.8 and alpha of 0.05, sample size would be 85.
For t-Test, given a power 0.8 and alpha 0.05, we estimate that we could detect a difference of 10% from a mean of − 20% OCR given S.D. of 18% with 51 samples.