Evaluation of Vital Signs’ Fluctuations and Behavioral Responses in the Assessment of Pain in Patients With Traumatic Brain Injury

Background Traumatic brain-injured (TBI) patients suffer severe pain. The assessment of behavioral responses and vital signs seems to be necessary for pain detection in these patients, a matter that this study aims to evaluate. Methods This cross sectional study uses repeated measures and included ninety-seven TBI patients from Poorsina hospital, Rasht, Iran. Patients’ relevant parameters were recorded using demographic checklist, specications related to the disease, RASS, CPOT, and FPT tools. The data subsequently were entered into SPSS software V. 21 and were analyze using several tests including Bonferroni’s inferential test and Greenhouse-Geisser test, multiple analysis regression coecient and general linear model by GEE method. The average age of patients was 42.3 ± 18.2. The average consciousness level was 9.30 ± 2.96. There was signicant difference between the painful and non-painful stimulations in heart rate, systolic blood pressure and diastolic blood pressure (p <0.001). Heart rate (p < 0.001, r = 0.253), number of respiration (p < 0.001, r = 0.173), systolic (p = 0.002, r = 0.128) and diastolic (p<0.001, r=0.223) blood pressures had a positive correlation with behavioral responses. However, the arterial oxygen saturation showed a negative correlation with behavioral responses (p < 0.001, r = -0.361). Statistical models demonstrated a signicant direct relationship between CPOT with heart rate (β = 2.39, p < 0.001) and both systolic blood pressure (β= 1.31, p=0.002) and the uctuations of diastolic blood pressure (β = 0.690, p = 0.009).


Conclusion
It seems that behavioral responses are appropriate indices for pain detection. However, vital signs are not capable of being considered as proper indexes for pain assessment since they changed during several procedures while remained unchanged in other tests. Background Traumatic brain injury (TBI) is a physiological disorder of brain function due to strike and results in either chronic or acute disruption in brain neurological functions (1, 2). Short-term memory loss, change in mental condition immediately after the injury (such as amnesia, anxiety, and wandering), and focal neurological defects are known to be the brain post-traumatic complications (3). TBI is considered one of the main causes of disability worldwide as the number of traumatic brain-injured patients indicates that 200,000 cases need to be hospitalized in the intensive care unit (ICU) each year. Moreover, 1.74 million patients with mild TBI need to be urgently visited by a doctor and cured (4,5).
Pain is the main concern in patients injured with brain trauma since they experience severe pain and it can alter the natural blood ow and nally increase the risk of brain damage (6,7). TBI patients are usually prescribed high dosages of analgesic or nervous blocking agents in order for the risk of brain edema to reduce (8). However, the use of these medicines provides a challenge for pain assessment because high dosages of analgesic medicines (such as sleeping aids and benzodiazepines) decrease patients' responses to the sensory stimulations and nervous blocking agents cause paralysis. On the other hand, the medicines of both groups have no bene cial effects on pain. As a result, the existence of pain cannot be denied in TBI patients, making the assessment of pain crucial in these patients (9).
Overall, the assessment and of pain and its appropriate treatment are known to be the main concerns in ICU because the majority of the patients are unable to articulate their pain. To address this problem, various methods such as the evaluation of vital signs' uctuations and behavioral responses are applied for pain assessment (10). vital signs' uctuations are de ned as any changes in body temperature, respiration, pulse rate, and blood pressure, all of which indicate one's health condition usually regulated by hemostatic and several normal domains (11,12). The analysis of behavioral responses to pain is another method by which pain can be evaluated in TBI patients admitted to ICU.  Pain behavior assessment tool (PBAT), behavioral pain scale (BPS), and critical care pain observation tool (CPOT) are used to analyze behavioral responses, with CPOT as one of the reliable measures (13). Numerous studies have proved the validity of COPT for ICU patients who are unable to self-report their pain (14). Gelinas et al. demonstrated that TBI cases have various facial expressions and psychological parameters compared to other patients (15). In a study conducted by Arbur et al. pain behaviors in critically ill TBI sufferers were described based on their conciseness levels (16). These behaviors included ushing, sudden eye-opening, moaning, and movement of extremities. A study on the identi cation of the sensitivity and speci city of (CPOT) for intubated patients who experienced bypass heart surgery showed that CPOT is a valuable tool for the assessment of painful procedures (such as suctioning) in ICU patients (17).
ICU TBI cases are usually not able to talk and self-report the intensity of their pain. Moreover, their related behaviors may be invisible or incomprehensible as a result of analgesic and nervous blocking medicines. Therefore, the evaluation of vital signs and behavioral responses seem to be necessary for ICU patients especially when taking contradictions of various studies into consideration (4,15). More research is needed to verify if monitoring for uctuations in vital signs can assist nurses in this di cult endeavor (18) . This study aims to monitor the uctuations of vital signs and behavioral responses during the evaluation of pain in TBI patients.

Methods
Population This is a cross sectional study with repeated measures in which the vital signs' uctuations have been detected in ninety-seven TBI patients hospitalized at the ICU section of PoorSina hospital, Rasht, Iran. Members of the population were chosen by consecutive sampling method. A sample size of fty-seven patients was determined using Cochran equation in which con dence level and test's power were considered 95% and 90%, respectively. Then, ve cases for each disturbing variable were added to the sample size according to the eight disturbing variables found in this study. The nal population size included ninety-seven patients.

Ethical considerations
To meet ethical considerations, the purpose of the study was explained to either patients or their companions, making them sure that patients' information will be kept anonymous and be used without their names or any pictures. This study was approved at the ethical committee of Guilan University of Medical Sciences, Rasht, Iran (IR.GUMS.REC-1396.88).

Inclusion criteria
Age ≥18, being hospitalized in ICU following TBI ≥ 24 hours, GCS≥13, the consent of the patients or their companions.

Exclusion criteria
Any kind of injury or any change in peripheral nervous (motor paralysis, spinal cord injury, or taking nervous blocking agents), any background for chronic drug misuse (based on the medical records), delirium (according to medical records), non-available medical information.

Data collection tools
In this study, data collection tools included demographic characteristics (age, gender, career, education), disease-related condition (detection, GCS, drowsiness level, type and dosage of analgesic and sedative medicines, and the cause, location, and intensity of pain). Drowsiness level was monitored using RASS. To begin with, patients were visited without any involvement and if conscious, the scores 0-4 were given to them. Unconscious patients were called by researchers and -1 to -3 points were considered based on their responses. When no response was observed, their shoulders were shaken and if there was no answer, their sternums were strongly squeezed and an appropriate point from -5 to -4 was recorded.
The severity of pain was detected using CPOT score. This checklist included ve categories of facial expression, body movements, muscle stretching, and the ability to talk in non-intubated patients, and adaptation to ventilation. Each behavior had (0-2) scores and the total scores were (0-8). A total score equal to zero was the minimum score and implied "without pain". Scores 1-3 and 4-5 de ned mild pain and moderate pain, respectively. The maximum scores (6 and above) belonged to uncontrolled severe pain. the sum of behavioral changes' scores were calculated by CPOT, a standard tool whose validity and reliability are proved in several studies (19,20) .
In this study, face pain thermometer (FPT) was used after either painful or non-painful stimuli and was prepared by the researcher. Vital signs' table (including heart rate, blood pressure, arterial blood oxygen, and respiration) was prepared before, during, and after both painful (change in position) and non-painful (non-invasive blood pressure (NIBP)) stimuli.

Data Collection
Patient's vital signs were incessantly monitored. NIBP was induced by lling the cuff when. Patients were visited during the NIBP procedure and the following position change as a non-painful stimulus. The supervision periods of 1 min, 2 mins, and 15 mins were carried out before, during, and after each procedure with total six evaluation items. At rst, patients were visited as a baseline (1 min) and vital signs, as well as behavioral responses, were recorded by a researcher. The accuracy of the evaluation was checked by the assistance of an expert who was asked to ll the CPOT forms separately. Then, the NIBP procedure was carried out and the patients were visited during the last two minutes and their items were recorded again before the nal record after 15 mins.
The ability to self-report was evaluated by directly asking patients without delirium who was able to communicate and had GCS ≥13 so that they would express the existence (yes/no) and the intensity (0-10 points) of their pain. Afterward, they were asked to score their pain using a 10-score pain scale. Following NIBP, the painful test was done and the vital signs were documented at 1, 2, and 15 mins. Moreover, the ability to self-report was assessed as NIBP test. It has to be mentioned that an expert supervised all stages and lled the CPOT forms separately.

Statistical analysis
The data were entered to SPSS V. 23 software. Qualitative variables were described using frequency and frequency percentage while quantitative variables were presented using mean, standard deviation, maximum, minimum, median, and con dence interval 95%. Mean, standard deviation, Bonferroni's test, and Greenhouse-Geisser test were used in order to compare behavioral responses before, during, and after both painful and non-painful stimuli. The potential relationships between pain and either behavioral responses or vital signs' uctuations were evaluated using multilinear regression for studied variables based on the general linear model using GEE method and with the control of disturbing factors. p<0.05 was considered as statistically signi cant.

Results
The average age of patients was 42.3 ± 18.2 years. The number of males was more than females (65.9%). Most of the patients had a freelance job (68.22%), and 80.36% had an academic education. Regarding the characteristics related to disease, the average consciousness level was 9.2 ±30.96, with 4 and 15 as maximum and minimum levels. The majority of the patients were unconscious (3.42%). The motorcycle accident was the main cause of the damage (98.65%), followed by fall casualties (23.7%). Damage in the frontal region was observed in most cases (27.42%) with high intensity (24.41%). Most of the patients did not receive either analgesic (98.6%) or sedative (41.8%) medicines. The mean drowsiness was 1.67 ± 2.01.
The evaluation of patients' ability of self-report and their behavioral responses before, during, and after using painful and nonpainful stimuli showed that 22.7% of cases felt pain after painful stimulation while 1% of them had no pain, and 76.3% were not able to express their pain because of GCS<13. Moreover, according to their self-reports after non-painful stimulation, 18.6% of the patients declared pain, 5.3% stated no pain. On the other hand, a majority of 76.3% were unable to state their pain (GCS<13) ( Table 1). MANOVA test showed signi cant difference between the painful and non-painful stimulations in heart rate, systolic blood pressure and diastolic blood pressure (p < 0.001) ( Table 2).
Using a non-painful stimulus, there was no signi cant difference in the number of respirations compared to reference time (p < 0.99). Yet, it signi cantly differed during and after painful stimulation compared to reference time (before painful stimulus) (p < 0.001), although no signi cant difference was seen in arterial oxygen saturation during the assessments compared to reference times (p < 0.05) ( Table 2).

Discussion
This study showed that heart rate is directly related to the painful stimulation compared to before and after using painful stimulus. These results are consistent with those of Aïssaoui et al. (21), Payen et al. (22), and Young et al (23). Our results highlight that heart rate can be considered as a pain indicator in TBI patients since pain activates the sympathetic system, releases epinephrine, and nally increases heart rate in patients laying back at ICU for a long time (22). Therefore, the heart rate can be an appropriate index for the detection of pain in TBI patients.
This study shows that the number of respiration increased signi cantly during and after painful motivation compared to reference time (before painful stimulus). This suggests that respiration rate may detect the severity of pain in TBI patients because different levels of pain especially chronic pain cause various responses in respiration such as changes in lung's volume as well as respiration rate and depth. The results found by Kapostina et al. were aligned with these outcomes (10).
Systolic and diastolic blood pressure increased only during painful stimulation compared to reference time. In a study by Young et al. a signi cant increase in blood pressure reported during a painful procedure (change in position) and a non-painful procedure (eye care) (23). However, Li et al. found no signi cant increase in systolic and diastolic blood pressure when imposing a painful procedure (24). This is why some pain experts do not recommend physiologic parameters such as blood pressure for the detection of pain (25,26). According to the present results, it seems that blood pressure is not capable of being a valuable index for pain detection in TBI patients since it varies in other conditions such as blood volume, blood viscosity, vascular elasticity, and peripheral resistance, the status of health muscles, genetic differences, diet, weight, activity level, and emotional status.
Present results regarding the distribution of behavioral responses (before, during, and after using a painful stimulation) in TBI patients showed a signi cant increase in behavioral responses during a painful stimulation procedure compared to the reference time. Likewise, similar results were found by Roulin et al (14). It should be noted that although behavioral responses proved to increase signi cantly as a result of both painful and non-painful stimuli, the scores of behavioral responses doubled during a painful stimulus comparing before it had been used. Le et al. declared that TBI patients showed more responses following the change in position or during NIBP (27). Moreover, a study by Joffe et al. demonstrated that CPOT scores were considerably increased when patients were moved compared to the time when they were gently touched (28). Our results showed that behavioral responses may be valuable indicators of pain assessment in TBI patients. Likewise, American nursing society and the society of critical care suggest behavioral responses for pain detection in patients who are not able to express their pain since these responses rely on the individual pain tolerance and usually manifest in appearance and body movements such as squeezing teeth, holding the painful part, bending, moaning, crying, and uneasiness (29).
Furthermore, behavioral responses proved to increase signi cantly during non-painful stimulus and after non-painful stimulus. In contrast, Kapoustina et al. reported that his most popular response during three assessment related NIBP was neutral. In their study, several reactions including eye-opening and no resistance to non-active non-vocal movement during both painful and nonpainful stimulation procedures were observed equally (10). Moreover, the behaviors in rest condition did not change in response to non-painful procedure and during NIBP, as Lee et al. reported (27). As numerous tools including pain behavioral assessment tool (PBAT), pain behavioral tool( PBS), and critical pain observation tool (CPOT) which is one of the most straightforward methods (13) and use in this study , the inconsistency between their results and our study can be attributed to the instruments and tools used in the detection of behavioral responses.
Unknown background of any underlying disease and lack of patients' background can be considered as the limitations of this study.

Conclusions
According to the present study, it can be concluded that there is a relationship between behavioral responses or vital signs' uctuations and pain. Since behavioral responses change in all procedures that were expected to be painful for patients, it can be deduced that these responses may be bene cial indicators for pain. However, vital signs do not seem to be appropriate to be considered as pain indices because several signs uctuate during some tests while others remained unchangeable. In conclusion, behavioral responses and several vital signs may be promising indicators of pain. The study was conducted in accordance with the ethical principles and its protocol was approved by the Ethics Committee of Guilan University of Medical Sciences (ethical code: IR.GUMS.REC-1396.88).

Consent for publication: Not applicable
Availability of data and materials: The datasets used and /or analyzed during the current study are available from the corresponding author on reasonable request