Association between general anesthesia in early childhood and neurodevelopment up to 4 years of age: the Japan Environment and Children's Study.

PURPOSE: The effects of general anesthesia on neurodevelopment in children remain controversial. We explored the relationship between general anesthesia and neurodevelopment in children participating in the Japan Environment and Children's Study (JECS). METHODS: This study enrolled children born between 37 and 41 weeks of pregnancy via single-vaginal delivery to pregnant women registered in the JECS between January 2011 and March 2014. Data were collected from mother-completed questionnaires and medical transcripts. Neurodevelopment in five domains was assessed every 6 months between 12 and 48 months of age, using the Ages and Stages Questionnaires. The associations between general anesthesia exposure during early childhood and neurodevelopment in children were evaluated at each time point. Adjusted odds ratios and 95% confidence intervals were estimated after covariate adjustment using logistic regression models. RESULTS: Children who received general anesthesia before age 1 year had higher risks of neurodevelopmental delay in all five domains throughout the observational period. The largest risk was for gross motor delay at 18 months (adjusted odds ratio: 3.51; 95% confidence interval: 2.75-4.49). The effects on the incidence of neurodevelopmental delays after age 3 were not observed except for problem solving at 48 months. The risk of neurodevelopmental delay in children who first received general anesthesia after age 1 was considerably small. CONCLUSIONS: This study suggests that general anesthesia administration before age 1 is associated with neurodevelopmental delay during 1-4 years of age. The risk of general anesthesia after age 1 may be small.

Associations between intraoperative nociceptive response index and early postoperative acute kidney injury in patients undergoing non-cardiac surgery under general anesthesia: a single-center retrospective cohort study.

Both tissue hypoperfusion and elevated surgical stress during surgery are involved in the pathogenesis of postoperative acute kidney injury (AKI). Although intraoperative hypotension, which evokes renal hypoperfusion, has been reported to be associated with the development of postoperative AKI, there is no consensus on the association between surgical stress responses (e.g., hypertension and inflammation) and postoperative AKI. Given that intraoperative values of nociceptive response (NR) index are reportedly associated with surgical stress responses, the present study was performed to assess associations between intraoperative NR index and postoperative AKI in patients undergoing non-cardiac surgery. In this single-institutional retrospective cohort study, data of the highest and lowest values of NR index during surgery were obtained in consecutive adult patients undergoing non-cardiac surgery under general anesthesia from February 2022 to August 2023. Data on highest and lowest mean blood pressure (MBP) during surgery were also obtained. In 5,765 patients enrolled, multivariate regression analysis revealed that the development of early postoperative AKI was significantly associated with highest NR during surgery ≥ 0.920, lowest MBP during surgery < 54 mmHg, age ≥ 48 years, male sex, ASA-PS ≥ III, emergency, and duration of surgery ≥ 226 min. In addition to intraoperative hypotension, a higher level of intraoperative NR index is likely associated with higher incidence of early postoperative AKI in adult patients undergoing non-cardiac surgery under general anesthesia.

The Impact of Nociception Monitor-Guided Multimodal General Anesthesia on Postoperative Outcomes in Patients Undergoing Laparoscopic Bowel Surgery: A Randomized Controlled Trial.

BACKGROUND: Excess surgical stress responses, caused by heightened nociception, can lead to elevated levels of postoperative inflammation, resulting in an increased incidence of complications after surgery. We hypothesized that utilizing nociception monitor-guided multimodal general anesthesia would exert effects on postoperative outcomes (e.g., serum concentrations of C-reactive protein (CRP) after surgery, postoperative complications). METHODS: This single-center, double-blinded, randomized trial enrolled ASA class I/II adult patients with normal preoperative CRP levels, scheduled for laparoscopic bowel surgery. Patients were randomized to receive either standard care (control group) or nociception monitor-guided multimodal general anesthesia using the nociceptive response (NR) index (NR group), where NR index was kept below 0.85 as possible. The co-primary endpoint was serum concentrations of CRP after surgery or rates of 30-day postoperative complications (defined as Clavien-Dindo grades ≥ II). MAIN RESULTS: One hundred and four patients (control group, n = 52; NR group, n = 52) were enrolled for analysis. The serum CRP level on postoperative day (POD) 1 was significantly lower in the NR group (2.70 mg·dL-1 [95% confidence interval (CI), 2.19-3.20]) than in the control group (3.66 mg·dL-1 [95% CI, 2.98-4.34], p = 0.024). The postoperative complication rate was also significantly lower in the NR group (11.5% [95% CI, 5.4-23.0]) than in the control group (38.5% [95% CI, 26.5-52.0], p = 0.002). CONCLUSIONS: Nociception monitor-guided multimodal general anesthesia, which suppressed intraoperative nociception, mitigated serum concentrations of CRP level, and decreased postoperative complications after laparoscopic bowel surgery.

Age-related changes in intraoperative mean values of nociceptive response in patients undergoing non-cardiac surgery under general anesthesia: A retrospective cohort study.

Intraoperative nociception is affected by preoperative factors, surgical invasiveness, and anesthesia. Although age-related changes in nociception in conscious humans have been well examined, those in intraoperative nociception in unconscious patients under general anesthesia are unknown. To clarify associations between age and intraoperative nociception under general anesthesia, we performed a retrospective cohort study in consecutive patients of all ages undergoing non-cardiac surgery under general anesthesia from January 2019 to July 2023. The intraoperative nociception value in each surgery was assessed by the averaged value of nociceptive response (mean NR) index during surgery. Patient characteristics, including age, sex, body mass index (BMI), emergent surgery, preoperative serum C-reactive protein (CRP) level, and comorbidities were also collected. After excluding patients with missing data of CRP and mean NR index, 22,061 patients were enrolled, and were divided into low, intermediate, and high surgical risk groups. Multivariable regression analysis showed a significant association between age and mean NR index in all three surgical procedure risk groups. The preoperative variables of CRP levels, BMI, emergent surgery, atrial fibrillation, renal failure, and long-term steroid use also showed significant associations with mean NR index in all three groups. Sensitivity analysis showed that intraoperative mean NR index was higher in younger children than that in both older children and younger adults, and it gradually increased again in older adults to the same level as in younger children. In conclusion, there is likely an association between age and intraoperative mean NR index in patients under general anesthesia.

Outcomes of Pain Management Training for the Fourth- and Fifth-Year Medical Students.

Pain management is a major medical issue. However, current medical education in Japan is inadequate with regard to training students to properly assess patients with acute and chronic pain and plan their treatment. Therefore, starting in 2019, Hyogo Medical University established a multidisciplinary educational system to better train medical students to provide pain care. The course, called clinical pain study, is offered to fourth- and fifth-year medical students. Fourth-year students learn the scientific aspects of pain through clinical practice. In this study, we assessed students' understanding of pain management based on the results of pretests and posttests performed before and after their practicum. These tests were administered from November 2019 to April 2022 to 263 fourth- and fifth-year medical students who took the clinical pain study class. The test results were compared in terms of the percentage of correct answers and the total score for each question using McNemar's chi-square test and paired t-tests, respectively. The results showed a significant improvement in the mean of the total score, confirming the improvement in medical students' knowledge (6.43 vs. 7.35 points; p < 0.001). Based on the results, overall, pain education at the university has had positive outcomes and will therefore be continued in the future.

Intraoperative nociception and postoperative inflammation associated with the suppression of major complications due to thoracic epidural block after pleurectomy/decortication for malignant pleural mesothelioma under general anesthesia: A retrospective observational study.

A recent study showed that thoracic epidural block (TEB) suppressed the occurrence of major complications after pleurectomy/decortication (P/D) for malignant pleural mesothelioma (MPM) under general anesthesia. To investigate the mechanisms underlying the correlation, both acute inflammatory status and intraoperative nociception were evaluated in the present study. In a single-institutional observational study, consecutive adult patients undergoing P/D were enrolled from March 2019 to April 2022. Perioperative acute inflammatory status was evaluated using differential White blood cell (WBC) counts and serum concentration of C-reactive protein (CRP) both before and after the surgery on postoperative day (POD) 1. The averaged value of nociceptive response index during surgery (mean NR) was obtained to evaluate the level of intraoperative nociception. Multivariable logistic regression analysis was performed to determine the association between perioperative variables and major complications Postoperative major postoperative complication was defined as Clavien-Dindo grades ≥ III. We conducted this study with 97 patients. After logistic regression analysis showed that general anesthesia without TEB was a sole risk factor for major complications, patients were divided into 2 groups: general anesthesia with and without TEB. The incidence of major complications was significantly lower in patients with TEB (33.3%, n = 33) than in those without TEB (64.1%, n = 64, P < .01). Although there was no significant difference in the CRP level between 2 groups, the lymphocyte-to-monocyte ratio (LMR) on POD 1 in patients with TEB was significantly higher than that in patients without TEB (P = .04). The mean NR was significantly lower in patients with TEB than that in those without TEB (P = .02). Both lower mean NR during surgery and higher LMR on POD 1 are likely associated the suppression of major complications due to TEB after P/D under general anesthesia. Decreases in the postoperative acute inflammatory response, caused by the reduction of intraoperative nociception due to TEB, may help suppress major complications after P/D.

Intraoperative Assessment of Surgical Stress Response Using Nociception Monitor under General Anesthesia and Postoperative Complications: A Narrative Review.

We present a narrative review focusing on the new role of nociception monitor in intraoperative anesthetic management. Higher invasiveness of surgery elicits a higher degree of surgical stress responses including neuroendocrine-metabolic and inflammatory-immune responses, which are associated with the occurrence of major postoperative complications. Conversely, anesthetic management mitigates these responses. Furthermore, improper attenuation of nociceptive input and related autonomic effects may induce increased stress response that may adversely influence outcome even in minimally invasive surgeries. The original role of nociception monitor, which is to assess a balance between nociception caused by surgical trauma and anti-nociception due to anesthesia, may allow an assessment of surgical stress response. The goal of this review is to inform healthcare professionals providing anesthetic management that nociception monitors may provide intraoperative data associated with surgical stress responses, and to inspire new research into the effects of nociception monitor-guided anesthesia on postoperative complications.

Association between averaged intraoperative nociceptive response index and postoperative complications after lung resection surgery.

OBJECTIVES: Since postoperative complications, defined as Clavien-Dindo grade ≥II, correlate with long-term survival after lung resection surgery in patients with primary lung cancer, identification of intraoperative risk factors for postoperative complications is crucial for better perioperative management. In the present study, we investigated the possible association between intraoperative variables for use in anaesthetic management and Clavien-Dindo grade ≥II. METHODS: In this multi-institutional observational study, consecutive adult patients undergoing video-assisted thoracic surgery for primary lung cancer under general anaesthesia from March 2019 to April 2021 were enrolled. All patients were divided into 2 groups with Clavien-Dindo grade

Associations between insomnia and central sensitization in cancer survivors undergoing opioid therapy for chronic cancer pain: A STROBE-compliant prospective cohort study.

Several risk factors for insomnia in cancer patients have been recognized, including chronic pain and treatment with opioid. Although associations between insomnia and central sensitization were previously reported in patients with chronic non-cancer pain, those have not been elucidated among cancer survivors undergoing opioid therapy for chronic cancer pain. To investigate the associations between insomnia and central sensitization among cancer survivors undergoing opioid therapy for chronic cancer pain, consecutive patients undergoing chemotherapy with chronic cancer pain under opioid therapy on an outpatient basis were enrolled from September 2019 to August 2020 and answered questions from the Athens Insomnia Scale (AIS) for assessing insomnia. Pain characteristics, including pain intensity, neuropathic pain, central sensitization assessed using the central sensitization inventory (CSI), opioid use disorder, and pain-related psychological symptoms were also examined. Uni- and multivariate regression analyses were performed to elucidate correlations between the AIS score and these pain characteristics. Of 44 enrolled patients, 20 patients completed to answer all questions. Insomnia was identified in 9 patients (45%). Although AIS scores showed no significant associations with pain intensity, neuropathic pain, opioid use disorder, or psychological symptoms, multivariate regression analysis revealed that CSI scores showed a positive relationship with AIS scores (P = .004). Discrimination was assessed using linear regression analysis which confirmed a significant association between the AIS and CSI scores (P = .002). Insomnia appears to be associated with central sensitization in cancer survivors with chronic cancer pain under opioid therapy.

Association of epidural analgesia during labor with neurodevelopment of children during the first three years: the Japan Environment and Children's Study.

BACKGROUND: Epidural analgesia relives pain during labor. However, the long-term effects on neurodevelopment in children remain unclear. We explored associations between exposure to epidural analgesia during labor and childhood neurodevelopment during the first 3 years of life, in the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: Pregnant women were recruited between January 2011 and March 2014, and 100,304 live births of singleton children born at full-term by vaginal delivery, and without congenital diseases were analyzed. Data on mothers and children were collected using a self-administered questionnaires and medical record transcripts. The children's neurodevelopment was repeatedly assessed for five domains (communication, gross motor, fine motor, problem solving, and personal-social), using the Ages and Stages Questionnaires, Third Edition, at six time points from age 6 to 36 months. After adjusting for potential confounders, the associations between exposure to epidural analgesia during labor and children's neurodevelopment at each time point were assessed. RESULTS: Of the 42,172 children with valid data at all six time points, 938 (2.4%) were born to mothers who received epidural analgesia during labor. Maternal exposure to epidural analgesia was associated with neurodevelopmental delays during the first 3 years after birth. Delay risks in gross and fine motor domains were the greatest at 18 months (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.40 [1.06, 1.84] and 1.54 [1.17, 2.03], respectively), subsequently decreasing. Delay risks in communication and problem-solving domains were significantly high at 6 and 24 months, and remained significant at 36 months (aOR [95% CI]: 1.40 [1.04, 1.90] and 1.28 [1.01, 1.61], respectively). Exposure to epidural analgesia was also associated with the incidence of problem solving and personal-social delays from 18 to 24 months old. Neurodevelopmental delay risks, except for communication, were dominant in children born to mothers aged ≥30 years at delivery. CONCLUSIONS: This study showed that maternal exposure to epidural analgesia during labor was associated with neurodevelopmental delays in children during the first 3 years after birth.

Association between thoracic epidural block and major complications after pleurectomy/decortication for malignant pleural mesothelioma under general anesthesia.

INTRODUCTION: A curative-intent surgical procedure, pleurectomy/decortication, for malignant pleural mesothelioma is accompanied by a high incidence of major postoperative complications. Although epidural block, which suppresses nociception during and after surgery, reportedly has both benefits and disadvantages in terms of outcomes after thoracic surgery for other diseases, the effects of epidural block on major complications after pleurectomy/decortication have not been evaluated. The aim of this study was to evaluate the association between epidural block and major postoperative complications following pleurectomy/decortication. METHODS: In a single-institutional observational study, consecutive adult patients undergoing pleurectomy/decortication under general anesthesia were enrolled from March 2019 to December 2021. Multivariable logistic regression analysis was performed to determine the association between perioperative variables and major complications. Next, patients were divided into two groups: general anesthesia with and without epidural block. Incidences of major postoperative complications, defined as Clavien-Dindo grades≥III, were compared between groups. RESULTS: In all patients enrolled with American Society of Anesthesiologists (ASA) physical status II or III (n=99), general anesthesia without epidural block was identified as a sole risk factor for major complications among perioperative variables. The incidence of major complications was 32.3% (95% CI 19.1% to 49.2%) in patients with epidural block (n=34), which was significantly lower than 63.1% (95% CI 50.9% to 73.8%) in patients without epidural block (n=65). In sensitivity analysis in patients with ASA physical status II alone, the same results were obtained. CONCLUSION: Epidural block is likely associated with reduction of the incidence of major complications after pleurectomy/decortication for malignant pleural mesothelioma under general anesthesia.

Quantitative evaluation of the effects of interscalene block on physiological responses to the balance between nociception and anti-nociception among inpatients undergoing total shoulder arthroplasty under general anesthesia.

Although the suppression of physiological responses to the balance between nociception caused by surgical trauma and anti-nociception due to anesthesia during total shoulder arthroplasty (TSA) is relevant for better perioperative managements, quantitative evaluations of the effects of ultrasound-guided interscalene brachial plexus block (ISB) on physiological responses have not been performed. Physiological responses were assessed using the nociceptive response (NR) index. In this multi-institutional observational study, associations between ISB and NR values were examined among inpatients undergoing TSA under general anesthesia between March 2019 and January 2021. The effects of ISB on acute postoperative pain and major complications within 30 days after surgery were also examined. NR values after skin incision clearly showed significant suppressions of physiological responses in patients undergoing TSA with ISB (n = 60), compared to those without ISB (n = 24). Acute postoperative pain on the day of surgery was also significantly less in patients with ISB than in those without ISB. Postoperative complications, classified by Clavien-Dindo grades, showed no significant differences between patients with and without ISB. A propensity score-matched sensitivity analysis confirmed the same results in patients with (n = 21) and without ISB (n = 21). In conclusion, suppression of physiological responses to the balance between nociception and anti-nociception by ISB can be quantitatively evaluated by NR index during TSA.

Imaging evaluation of continuous extrapleural intercostal nerve block for minimally invasive cardiac surgery: a case report.

BACKGROUND: Spinal nerve block is difficult with minimally invasive cardiac surgery (MICS), because of the risk of serious bleeding complications due to full heparinization. Continuous extrapleural intercostal nerve block (CEINB) is a postoperative pain treatment for intercostal thoracotomy, with fewer complications. Here, we report a case in which imaging evaluation of CEINB with contrast medium was conducted to anatomically confirm the spread of local anesthetics after MICS. CASE PRESENTATION: A 65-year-old woman with severe mitral regurgitation underwent mitral valve plasty under general anesthesia via right-sided mini-thoracotomy. A CEINB catheter was placed before the incision was closed, without creating a conventional extrapleural pocket. We conducted an imaging evaluation with a contrast medium via the inserted catheter and confirmed sufficient spread around the intercostal nerve area. In addition, postoperative pain was well controlled by the nerve block. CONCLUSIONS: Imaging evaluation of CEINB with contrast medium could increase analgesic quality and decrease complications post-MICS.

Intra-operative nociceptive responses and postoperative major complications after gastrointestinal surgery under general anaesthesia: A prospective cohort study.

BACKGROUND: Surgical procedures stimulate nociception and induce physiological responses according to the balance between nociception and antinociception. The severity of surgical stimuli is associated with major postoperative complications. Although an intra-operative quantitative index representing surgical invasiveness would be useful for anaesthetic management to predict and prevent major complications, no such index is available. OBJECTIVES: To identify associations between major complications after gastrointestinal surgery and intra-operative quantitative values from intra-operative nociception monitoring. DESIGN: A multi-institutional observational study. SETTING: Two university hospitals. PATIENTS: Consecutive adult patients undergoing gastrointestinal surgery under general anaesthesia. MAIN OUTCOME MEASURES: Averaged values of nociceptive response index from start to end of surgery (mean NR index) and risk scores of the Surgical Mortality Probability Model (S-MPM) were calculated. Pre and postoperative serum C-reactive protein (CRP) levels were obtained. After receiver-operating characteristic (ROC) curve analysis, all patients were divided into groups with high and low mean nociceptive response index. Associations between mean nociceptive response index and postoperative major complications, defined as Clavien-Dindo grade at least IIIa, were examined using logistic regression analysis. RESULTS: ROC curve analysis showed a nociceptive response index cut-off value for major complications of 0.83, and we divided patients into two groups with mean nociceptive response index less than 0.83 and at least 0.83. The incidence of major complications was significantly higher in patients with mean nociceptive response index at least 0.83 (23.1%; n = 346) than in patients with mean nociceptive response index less than 0.83 (7.7%; n = 443; P < 0.001). Multivariate analysis revealed emergency surgery, S-MPM risk score, mean nociceptive response index and postoperative CRP levels as independent risk factors for major complications. CONCLUSION: Mean nociceptive response index during surgery likely correlates with major complications after gastrointestinal surgery. TRIAL REGISTRATION: The current observational study had no intervention, and was therefore, not registered.

Three-day tracheal intubation manikin training for novice doctors using Macintosh laryngoscope, McGRATH MAC videolaryngoscope and Pentax AirwayScope.

BACKGROUND: We compared the intubation skills obtained by novice doctors following training using 3 instruments, the conventional Macintosh laryngoscope (Mac) and 2 types of indirect video-laryngoscopes (McGrathTM-MAC: McGrath (McG) and AirwayScope (AWS)), to determine the most appropriate instrument for novice doctors to acquire intubation skills, especially focusing on visual confirmation of vocal cords, during a 3-day intensive manikin training program. METHODS: Fifteen novice doctors who did not have sufficient experience in endotracheal intubation (ETI) and consented to participate in this study were included. We used AirSim and AMT (Airway management Trainer) manikins. First, an experienced anesthesiologist instructed the trainees on using the 3 instruments for a few minutes. Then, after familiarizing themselves with each device for 10 minutes, the participants attempted ETI on the 2 manikins with the 3 devices used in random order. Intubations with each device were practiced and performed for 3 successive days. We assessed the percentage of glottic opening (POGO) score, successful intubation rate and tracheal intubation time for each participant, with each device, and on each day. RESULTS: In the first manikin, AirSim, POGO scores in the McG and AWS groups were significantly higher than those in the Mac group on all 3 days (P < .0001). The number of intubation failures in the Mac group decreased from 2 cases on day 1, to 1 case on day 2 and zero cases on day 3. There were no failures in the McG and AWS groups on any of the days. With the second manikin, AMT, POGO scores in the Mac group were significantly lower than those in the McG and AWS groups on all 3 days. There were no intubation failures in the AWS group on all 3 days. In the Mac group, the number of intubation failures decreased from 3 on day 1, to 2 on day 2 and zero failures on day 3. In the McG group, there were only 3 failures on day 1. CONCLUSION: The 2 types of indirect video-laryngoscopes (McGRATH and AirwayScope) were demonstrated to be suitable instruments for novice doctors to achieve higher POGO scores in a 3-day intensive ETI training.

Association between intraoperative nociception and surgical invasiveness in patients undergoing non-cardiac surgery under general anesthesia: a retrospective cohort study.

There are several indexes of intraoperative nociception during surgery under general anesthesia. Although a higher degree of surgical invasiveness increases intraoperative nociception, an association between the index of intraoperative nociception and severity of surgical invasiveness has not been reported. We hypothesized that there is associations between averaged values of nociceptive response (NR) throughout surgery (mean NR), as the index of intraoperative nociception, and surgical severity codes in the Surgical outcome risk tool (SORT) or procedure risk codes in the Surgical mortality probability model (S-MPM). The primary outcome was the association between mean NR and severity scores of surgical procedure. Hence, a single institutional retrospective cohort study was performed in consecutive patients undergoing non-cardiac surgery under general anesthesia from June 2018 to May 2019. There were significant increases in the three categories of procedure risk in the S-MPM corresponding to the increase in mean NR values in 5090 patients. In the SORT, the highest intensity in the four categories of surgical severity also significantly correlated with the increase in mean NR values. Increasing intensity of intraoperative nociception is likely associated with higher severity codes of surgical invasiveness in prediction models for postoperative morbidity and mortality.

Modified model for predicting early C-reactive protein levels after gastrointestinal surgery: A prospective cohort study.

BACKGROUND: Postoperative serum concentration of C-reactive protein (CRP) is one of the objective quantitative indices integrating the effects of preoperative and intraoperative variables. Higher levels of CRP after gastrointestinal surgery are associated with major postoperative complications. To develop a model for predicting CRP levels on postoperative day (POD) 1 in surgical patients both with and without serious conditions and comorbidities, we modified the previous formula for prediction of CRP levels on POD1, and assessed the accuracy of our modified predictive formula for CRP levels. MATERIAL AND METHODS: Consecutive patients of all ages undergoing gastrointestinal surgery under general anesthesia were enrolled in this single-institution prospective cohort study. We developed a modified predictive formula in a calculation cohort. Next, associations between measured CRP levels on POD1, predicted CRP levels on POD1 using the previous and modified models, and major complications after surgery were examined in a validation cohort. RESULTS: We obtained the following model in the calculation cohort (n = 222): Modified model for predicting CRP levels on POD1 (mg•dL-1) = -10.13 + 0.0025 Duration of surgery (min) + 15.9 Mean Nociceptive Response (NR) + 0.66 Preoperative CRP level (mg•dL-1). In the validation cohort (n = 440), there was a significant association between measured and predicted CRP levels on POD1 (P < 0.001) No significant difference between the measured and predicted CRP levels using the modified model was observed (P = 0.847). There were also significant associations between the predicted CRP levels and major complications after surgery. CONCLUSION: CRP levels predicted using duration of surgery, mean NR, and preoperative CRP levels are likely identical to measured CRP levels on POD1, being associated with major complications after gastrointestinal surgery.

Mathematical evaluation of responses to surgical stimuli under general anesthesia.

Surgical invasion activates nociception, while anesthesia suppresses it. Under general anesthesia, stimulation, which is the balance between nociception and anti-nociception, induces responses, including activation of the autonomic nervous system. To evaluate the associations between stimulation (S) and the resultant responses (R), we examined R values, which were calculated using mathematical models of Stevens' power law, Gompertz function and logistic function. The previously developed Nociceptive Response (NR) formula was applied as a modified logistic model. S values were calculated using a linear function in the NR formula. In a retrospective study, we developed an exponential model of Stevens' power law and a sigmoidal model of Gompertz function using differential equations, by adjusting R values to correspond to NR values, in consecutive patients undergoing surgery under general anesthesia (n = 4,395). In a subsequent prospective study, we validated the superiority of R values of Gompertz function and the NR formula in an exponential model in adult patients undergoing tympanoplasty (n = 141) and laparoscopic cholecystectomy (n = 86). In conclusion, both modified logistic function and Gompertz function are likely appropriate mathematical models for representing responses to stimulation resulting from the balance between nociception/anti-nociception during surgical procedures under general anesthesia.