On The Bright Side of Life - The Effect of Ambient Light Intensity on Postsurgical Patient-Reported Outcomes


 Light intensity affects humans in multiple ways. We aimed to characterize the potential impact of light intensity on patients’ pain management experience in the perioperative setting. Within the German multicenter registry project QUIPS, we collected patient reported outcomes (PROs) concerning pain and side effects, demographics and perioperative pain medication, and measured the light intensity in their rooms on the first postoperative day. Primary endpoint was maximum pain intensity rated on the numerical rating scale (NRS, 0-10). Secondary endpoints were pain intensity during movement, mood, nausea, tiredness and satisfaction. Measurement of light intensity was done with a calibrated light meter. For analysis, we used linear and log-linear regression models with age, gender, pre-existing chronic pain, ASA status, and logarithmized light intensity as independent variables. Data of 539 surgical patients from 9 hospitals were included. We found no significant effect of light intensity on the primary endpoint. However, we observed a strong positive correlation between nausea and light intensity. Perspective: Our study indicates that further investigations about the clinical importance of light exposure with regard to nausea and other medical conditions might be worthwhile.Trial registration: QUIPS is registered in the German Clinical Trials Register (DRKS00006153)


Introduction
Light is defined as optical radiation entering the eye that provides visual sensation in humans. The effects of light fall into two categories: those modifying the individual endocrine, hormone, and metabolic state by light reaching the retina and those resulting from light on the skin. According to this specific vision related definition, light has been increasingly related to a range of ocular circadian, neuroendocrine, neurobehavioral and therapeutic responses in humans. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( app. 480 nm) blue light [2]. Exposure to natural sunlight has been associated with improvement in mood, reduced mortality and decreased stress, pain and analgesic medication use and pain medication cost in patients who have undergone spinal surgery. [3] Among hormonal effects by light, the (reduced) secretion of melatonin from the pineal gland is the most important.
Moreover, the activity of serotonin n-acetyltransferase is reduced after exposure to light.
While light exposure elevates the serotonin levels and likewise reduces melatonin levels, serotonin might most likely act as a modulator of pain in the central nervous system. [4] Serotonin is a significant modulator of sensory input to the central nervous system; however, the only analgesics that selectively target G-protein-coupled 5-HT receptors are highly specific for treatment of headache. [4] Previous work has indicated that serotonin can both potentiate and inhibit primary afferent neurotransmission, and given that most subtypes of 5HT receptor are present in sensory ganglia, serotonin potentially has both pro-and antinociceptive effects through modulation of primary afferent neurotransmission.
Postoperative pain is a major problem of modern medicine, confronting every hospital with structural, procedural and financial challenges. Extensive studies have demonstrated that many patients suffer from moderate to severe postoperative pain. [5], [6] Severe pain is associated with decreased patient satisfaction, delayed postoperative ambulation, increased incidence of chronic postoperative pain, [7] pulmonary [8], [9] and cardiac complications [10] and increased morbidity and mortality [11]. Options for treatment of acute, postoperative, as well as for chronic pain, are limited, and many drugs are marginally effective [13] and often accompanied by severe side effects.
Non-pharmacological options for the treatment of pain would be highly desirable and advantageous in safety, including lack of tolerance, somnolence, addiction, gastrointestinal disturbances and, perhaps, other factors such as convenience and cost. Light therapy has been reported to be useful for multiple medical conditions [14], for example to control depression, [15], [16] to increase daytime circadian stimulation, to improve sleep quality, and mitigate depression in Alzheimer disease [17]. Exposing patients to bright light of more than 6000 lux significantly improved seasonal affective disorder, a serious condition with increased risk of suicidality. An association has also been found between staying in a sunny room and a decreased need for analgesic medication following surgery. Patients who were accommodated on the bright side of the hospital perceived less stress and required less analgesic medication than those on the dark side [18]. In addition, a market for substance free alternatives to relieve pain emerged, including light based products like LED-belts for back pain treatment.
These findings indicate a physiological relationship of pain perception and lighting condition.
However, this relationship has not yet been studied in a larger number of patients. Therefore, the main objective of this study was to observe a potential association between ambient light intensity and pain-related patient-reported outcomes (PROs) in clinical postoperative routines.

Study design
This study was based on a prospective German multicentre registry named QUIPS (Quality Improvement in Postoperative Pain Treatment), which was started as a benchmark initiative to compare pain outcome parameters among participating German hospitals. The QUIPS project is supported by the German Societies and Professional Associations of anesthesiologists and surgeons [19]. Patients complete a validated 15-item QUIPS questionnaire on the first postoperative day. Patient reported data were gathered along with information on the type of surgery, anesthesia and pain treatment. Data assessment was carried out by trained study personnel. Data were collected in a standardized manner in randomly selected patients, unknown to the medical staff before data collection.
Patients were informed in written form as well as orally by the study personnel that data collection was voluntary and anonymous and that they could refuse to be included at any time. Informed consent was documented by filling in the questionnaire. The project was approved by the Ethics Committee as well as the Data Security Board of Jena University Hospital, Germany, and all participating sites obtained approval from their respective Ethics Committees.

Outcome and Influencing Variables
The primary outcome parameter was maximum pain intensity since surgery, measured with the numeric rating scale (NRS, 0=no pain, 10 = worst pain imaginable). Age, gender, preoperative chronic pain, pain during movement and ASA-score were selected as covariables in the analysis [20]. The secondary endpoints were mood, nausea, tiredness and satisfaction. These items are also part of the validated 15-item QUIPS questionnaire. The outcome satisfaction has been rated on a scale from 0 to 10 (0= low grade,10 = highest grade) while the other secondary outcome parameters nausea, tiredness etc. have been determined binary (yes/no).

Patients
Nine hospitals participated in the study, and patients having completed the QUIPS questionnaire between August 2015 and September 2016 were included. Patients were included if the assessment was done on the day after surgery and if the patient was 18 years or older and able to understand the study. Exclusion criteria were the patient (1) had been transferred to another ward after surgery; (2) was not present in his room or had been

Light Measurement
The light measurement was done with calibrated light meters (unit: lx) by a hand-held device (model PCE-172, manufactured by PCE Instruments, Southampton, UK) in every participating site. The light meter captures the luminous flux per surface unit of measure independent from its direction and extensiveness. The sensor has a spectral sensitivity which is adapted to the human photopic luminosity curve. Light intensity measurement was only executed on days with constant weather conditions between 9 am and 5 pm. Days with frequent changes between sunshine and clouds were not included in the light study. The measurement was conducted all year round to include seasonal dependencies on light intensity. The measurement of light intensity was performed by placing the sensor at the foot of the patients' bed.

Statistical Analysis
The analysis was performed using both logistic and linear regression models. We used logarithmic transformation in order to describe the distribution of light intensity values.
The primary and secondary outcomes were considered as dependent variables. Age, sex and preoperative pain were used as independent factors. For Integration of variables into the regression model, inclusion method was applied. Furthermore we used the same set of covariates including age, gender, chronic pain and asa score for our regression models.

Results
Data were collected from 539 surgical patients in 9 German hospitals for 14

Primary Outcome maximum pain
For the primary endpoint maximum pain intensity, no significant effect of light intensity was found (table 3). Age (p = 0,00) and gender (p = 0,01) had a significant effect on the outcome maximum pain intensity after surgery.  Table 3. Summary of statistical relation between maximum pain and age, gender, pre-existing chronic pain and light intensity.

Secondary Outcome -Tiredness, Satisfaction, Pain during movement
For the secondary endpoints of pain intensity during movement, satisfaction and tiredness no significant effect of light intensity was found. Furthermore, the data showed a significant connection of gender and tiredness ( p = 0,00, CI: 1,96 -4,19), while pain during movement and age (p = 0,00, CI: 0,96 -0, 990) were statistically correlated.

Discussion
To our knowledge, this is the first analysis of an association between ambient light intensity patients are known to suffer from hypersensitivity to light following lowered excitation thresholds in the central nervous system [22]. In addition, a more marked melatonin suppression after light exposure in migraine patients compared to controls suggests that the melatonin level plays a central role in the pathophysiology of migraine [23]. These findings emphasize the assumption that photoregulation of migraine headache is exerted by the nonimage-forming retinal pathway that modulates the activity of dura-sensitive thalamocortical neurons [24]. Finally, a recent study has shown that melatonin functioning as a biomarker for circadian dysregulation correlated with major depression and fibromyalgia symptom severity [25]. These findings manifest the hypothesis that lighting has a severe effect on neurohumoral pain transmission and encourage further research.
In context to our research design that emphasizes on acute postoperative pain there is no further evidence suggesting a significant effect of lighting conditions on pain intensity. Our findings could not provide further evidence on the main hypothesis. Explanation to our

5)
In correspondence with the results of former QUIPS analyses our data identified female gender, age and chronic pain and as confounders of the primary endpoint maximum pain regardless of the type of surgery. [20] 6) The Bonferri correction for maintaining an overall alpha-level of 0.05 was not implemented in our statistical analysis which could potentially raise the chance of false positive results.

Conclusion
Our data show no further evidence for light intensity-induced pain modulation in humans in the postoperative setting. For the secondary outcomes, the data showed an association between brighter light intensity and increased incidence of nausea for the first time.
The subject should be studied under more controlled conditions concerning the variability of the types of surgery, hospital analgesic standards and potential strong differences between sunlight and artificial light concerning intensity and wavelength.
The ideal study design would include measuring the light intensity average of a longer time span for a standardized sub group of patients undergoing similar or same surgical procedures. Furthermore, in order to have less variability, only patients from one ward with comparable lighting conditions and architecture should be included. Randomized controlled trials are needed to have further evidence for making an association between light intensity and acute pain intensity.