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.

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.

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.

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

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.

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.

Adrenal pheochromocytoma treated by combination of adrenal arterial embolization and radiofrequency ablation.

Combined therapy with adrenal arterial embolization and RF ablation may represent a useful therapeutic option with curative properties in select patients with pheochromocytoma.

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.

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.

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.

Effects of Simulation Study of High Neuraxial Block During Epidural Analgesia for Labor Pain on Pre/Posttest Evaluation in Junior Clinical Trainees.

BACKGROUND: Since a high neuraxial block is one of the serious complications in obstetric anesthesia, simulation training is required for the education of rapid diagnosis and treatment of this complication. OBJECTIVES: This study aimed to evaluate the effects of a simulation study of the high neuraxial block during epidural analgesia for labor pain on pre- and post-simulation tests in junior clinical trainees, who had graduated a medical school within one or two years and being under a two-month program for anesthesia during the Japanese Postgraduate Medical Education. METHODS: Twenty-two junior clinical trainees participated in this study from September 2016 to May 2017. Before the simulation training, the participants answered a pretest, providing written responses on "how to approach and treat the rapid spread of anesthesia (high neuraxial block) in painless epidural delivery" in a bullet-point form. The number of correct answers to 12 items was counted for each participant. These items were as follows: mask ventilation, preparation for tracheal intubation, oxygenation, supraglottic airway placement, checking the breathing, checking oxygen saturation using pulse oximetry, checking blood pressure, ephedrine injection, checking epidural tube, assessing the level of sensory block, assessing the level of consciousness, and left uterine displacement. After performing our original training, all participants were debriefed and written responses were obtained to a posttest containing the same content as the pretest. RESULTS: The percentage of correct answers significantly increased from 8.3 to 16.7% (P = 0.041) after training. The response rates for "mask ventilation" and "check epidural tube" significantly increased from 13.6 to 54.5% (P = 0.004) and from 4.5 to 27.3% (P = 0.039), respectively, after training. CONCLUSIONS: Simulation training is likely an effective method for junior clinical trainees on studying diagnosis and treatment of high neuraxial block during epidural analgesia in parturient patients.

Acute and chronic neuropathic pain profiles after video-assisted thoracic surgery: A prospective study.

Acute postsurgical pain, probably including acute neuropathic pain (ANeP), starts at the early postoperative period, and chronic postsurgical pain including chronic neuropathic pain (CNeP) persists at least 3 months after surgery. Although it must be important for prevention and treatment of acute and chronic postoperative pain to reveal the time course of postoperative neuropathic characteristics, a neuropathic pain profile after surgery has not been evaluated.Pain status at the surgical site in adult patients who underwent video-assisted thoracic surgery (VATS) for lung cancer was prospectively assessed until 12 months after surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire until 6 days after surgery and the DN2 questionnaire throughout the study.Twenty-seven patients were enrolled in this study. Pain intensity at surgical sites were significantly higher at 1 and 6 days after surgery during resting state, and were also significantly higher at 3, 6, and 12 months after surgery during movement than those before surgery. The incidence of ANeP was 33.3% at 1 day, and 18.5% at 6 days after surgery. The incidence of CNeP decreased to 12.5% at 3 months, 5.0% at 6 months, and 0.0% at 12 months after surgery. The number of neuropathic characteristics, assessed by DN2 scores, significantly increased at 1 and 6 days after surgery, compared to those before surgery. DN2 scores at 3, 6, and 12 months after surgery, however, showed no significant differences compared to those before surgery.In patients with acute postsurgical pain, 20% to 30% of patients show ANeP characteristics, and the incidence of CNeP gradually decreases after VATS in patients with chronic postsurgical pain.

Association between intraoperative nociception and postoperative complications in patients undergoing laparoscopic gastrointestinal surgery.

A higher degree of surgical invasiveness, which increases intraoperative nociception, might induce postoperative complications. Although several nociceptive indices for use during surgery are available in clinical practice, association between intraoperative nociception and postoperative complications has not been reported. An index representing intraoperative nociception, which is the averaged value of Nociceptive Response throughout the surgery (mean NR) was applied to examine the association in the present study. The retrospective study evaluated consecutive adult patients undergoing laparoscopic gastrointestinal surgery, American Society of Anesthesiologists-physical status (ASA-PS) I or II, whose preoperative C-reactive protein level was < 0.3 mg dL-1. We first used ordinal logistic analysis to examine the association between preoperative and intraoperative risk factors and complications graded by the Clavien-Dindo classification. Next, we performed propensity score matched analysis to evaluate the effects of mean NR throughout surgery on postoperative complications. Ordinal logistic analysis (n = 158) revealed that duration of surgery (P < 0.001), mean NR during surgery (P = 0.002), and ASA-PS (P = 0.016) were risk factors for postoperative complications. Then all patients were divided into two propensity score matched groups, based on a mean NR of < 0.85 and ≥ 0.85, with matching for age, ASA-PS, body mass index and duration of surgery. The severity of postoperative complications was significantly higher in the high NR group than in the low NR group (P = 0.005). In conclusion, there was likely an association between intraoperative nociception and postoperative complications in patients without serious preoperative conditions and comorbidities.