Predictive value of surgical pleth index for early postoperative pain in children undergoing general anesthesia: A prospective observational study

Predictive value of surgical pleth index for early postoperative pain in children undergoing general anesthesia: A prospective observational study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictive value of surgical pleth index for early postoperative pain in children undergoing general anesthesia: A prospective observational study Lin Li, Qinghua Meng, Weizhi Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6565979/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Oct, 2025 Read the published version in BMC Anesthesiology → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Postoperative pain is common in children during early recovering from general anesthesia, especially for pediatric patients undergoing adenotonsillectomy surgery. There is no valid tool to predict postoperative pain at present. Methods: One hundred and fifty patients aged 4–8 years, scheduled to undergo adenotonsillectomy surgery were enrolled in the clinical trial. All patients were given intravenous general anesthesia and endotracheal intubation by the same pediatric anesthesiologist. Surgical pleth index (SPI) monitoring for each patient was performed from the same shared SpO 2 measurement finger which was on the side opposite to the NIBP measurement through the CARESCAPE Monitor B650 (GE Healthcare, Helsinki, Finland). The SPI values, mean arterial pressure (MAP) and heart rate (HR) were recorded at each minute for five minutes immediately after surgery. The maximum values of SPI, MAP and HR (SPI max , MAP max and HR max respectively) were taken for analysis. Early postoperative pain was assessed for each patient using the modified Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) in postanesthesia care unit (PACU). Receiver-operating characteristics (ROC) curves and the associated areas under the curves (AUC) were computed to analyze the ability of SPI to predict early postoperative pain. Results: One hundred and thirty-two patients were included and analyzed finally. The SPI max , MAP max and HR max of the patients whose CHEOPS scores less than 4 were 43±6, 58±9mmHg and 90±12 beat/min while of the patients whose CHEOPS scores equal or greater than 4 were 54±8, 67±11mmHg and 96±13 beat/min respectively. The SPI (AUC: 0.84, 95% CI: 0.74-0.92, P<0.001) had a good predictive value for postoperative moderate-to-severe pain compared with MAP (AUC: 0.53, 95% CI: 0.41-0.67, P=0.58) and HR (AUC: 0.62, 95% CI: 0.46-0.76, P=0.19). The best-fit (highest combined sensitivity and specificity ) cut-off values of SPI to distinguish mild pain from moderate-to-severe pain was 46 with the sensitivity of 79.4% and specificity of 87.8%. Conclusions: SPI can effectively predict the occurrence of early postoperative moderate-to-severe pain in pediatric patients undergoing adenotonsillectomy surgery under general anesthesia. SPI might be one reliable pain assessment tool to guide pediatric anesthesiologists for timely identification and management of postoperative pain. Trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2200058658 (13/04/2022). Surgical pleth index postoperative pain children general anesthesia adenotonsillectomy surgery Figures Figure 1 Figure 2 Introduction Postoperative pain is common in children during early recovering from general anesthesia, especially for pediatric patients undergoing adenotonsillectomy surgery[ 1 – 3 ]. It is crucial to be able to assess postoperative pain in a timely and effective manner, because discomfort and other adverse events such as emergence agitation will be greatly reduced when postoperative pain is identified and treated as early as possible[ 4 – 7 ]. However, it is full of challenges to predict postoperative pain and deal with it in advance due to lack of reliable pain assessment methods and tools, especially for pediatric patients during early recovery from general anesthesia. At present, the administration of analgesics during surgery still relies on traditional methods based on changes in blood pressure and heart rate[ 8 ]. There have been no effective tools that can precisely monitor the depth of intraoperative analgesia and accurately predict the occurrence of postoperative pain. The surgical pleth index (SPI), first introduced in 2007, an index based on changes related to the balance between the sympathetic and parasympathetic nervous systems, has been used for assessment of nociception-antinociception balance[ 9 ]. SPI is a dimensionless, normalized score (0-100) which is based on an algorithm combining the pulse photoplethysmographic amplitude (PPGA) and the normalised heart beat interval (HBI), both obtained from pulse oximetry monitoring (GE Healthcare, Helsinki, Finland )[ 9 ]. Recently, the SPI has been used to monitor the surgical stress response and guide appropriate analgesic administration during general anesthesia[ 10 ]. It is related to surgical stimuli and the dosage of analgesics, and predicts the effect of pain stimulation and analgesic treatment more accurately than general clinical parameters[ 11 , 12 ]. An increasing number of studies have shown that SPI has the potential to reflect intraoperative noxious stimuli and guide the management of opioids in adult patients[ 13 – 15 ]. The evidence of SPI in guiding intraoperative analgesia and predicting postoperative pain in pediatric patients is scarce. The primary aim of this study was to evaluate the value of surgical pleth index to predict early postoperative pain in pediatric patients undergoing adenotonsillectomy surgery under general anesthesia. Methods Study design and Patients This was a prospective observational study conducted at Shanxi Provincial Children’s Hospital from October 2022 to May 2024. This study was approved by the Institutional Ethics Committee of Shanxi Provincial Children’s Hospital and registered on the Chinese Clinical Trials Registry (ChiCTR2200058658, April 13, 2022). Written informed consent was obtained from parents or legal guardians the day before data collection and surgery. One hundred and fifty patients aged 4–8 years, ASA physical status I or II, scheduled to undergo adenotonsillectomy surgery were enrolled in the clinical trial. Patients with a history of neurological or psychiatric disorders, cardiac arrhythmia, preoperative chronic pain, or a history of upper respiratory tract infection in the preceding 4 weeks were excluded. Patients who had recently used analgesic or sedative drugs, had a history of adverse reactions or allergies to anesthetic drugs, or had a history of abnormal anesthesia were also excluded from the study. The flow chart of this study is shown in Fig. 1 . Anesthetic technique All patients were given intramuscular injection of atropine 0.01mg/kg 30 min before surgery. After entrance to the operating room, noninvasive blood pressure (NIBP), electrocardiography (ECG), and pulse oximetry saturation (SpO 2 ) were monitored for each patient. General anesthesia was performed by the same pediatric anesthesiologist. Anesthesia induction was conducted by intravenous injection of sufentanil 0.4ug/kg, etomidate 0.3mg/kg and cisatracurium 0.15mg/kg sequentially. After spontaneous respiration disappeared, then intraoral endotracheal intubation was performed using video laryngoscope, and pressure-controlled ventilation mode (Drager Fabius GS premium, Germany) was executed. The fraction of inspired oxygen was 50%, and the inspiratory to expiratory ratio was 1:1.5. By adjusting the inspiration pressure and frequency, the end-tidal carbon dioxide partial pressure was maintained between 35 mmHg and 45 mmHg (1 mmHg = 0.133 kPa). General anesthesia was maintained by continuous infusion of propofol 6–10 mg/kg/h and remifentanil 0.3–0.5µg/kg/min. Parecoxib sodium 0.1mg/kg was given intravenously immediately at the beginning of surgery for each patient in order to achieve the effect of preemptive analgesia. The infusion of anesthetic drugs was stopped 5min before the end of surgery. Surgical pleth index monitoring Surgical pleth index (SPI) monitoring for each patient was performed from the same shared SpO 2 measurement finger which was on the side opposite to the NIBP measurement through the CARESCAPE Monitor B650 (GE Healthcare, Helsinki, Finland). The plethysmographic waveform was continuously recorded and reanalyzed to produce the normalized pulse plethysmographic amplitude (PPGAnorm), and the normalized heartbeat interval (HBInorm). SPI was computed as a combination of PPGAnorm and HBInorm: SPI = 100-(0.7×PPGAnorm + 0.3×HBInorm)[ 9 ]. The Monitor B650 displayed the SPI values between 0 and 100 directly. The SPI values, mean arterial pressure (MAP) and the heart rate (HR) were recorded at each minute for five minutes immediately after surgery. The maximum values of SPI, MAP and HR (SPI max , MAP max and HR max respectively) were taken for analysis. Evaluation of early postoperative pain All patients were sent to the postanesthesia care unit (PACU) for further observation after surgery and extubation. In the PACU, pain score was performed each 10min for a total of 3 times (10min, 20min and 30min after admission to PACU, the maximum score was taken for analysis). The pain score was determined using the modified Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS), which comprises five items including crying, facial, verbal, torso, and leg status that were summed to calculate a final pain score (range: 0–10)[ 16 ]. The final score of 0–3 is classified as no or mild pain, 4–6 as moderate pain, and 7–10 as severe pain. Children with moderate to severe pain (score ≥ 4 points) were treated with intravenous injection of sufentanil at 0.1ug/kg as a remedy. Statistical analysis The sample size was calculated using PASS software (version 15.0, NCSS statistical software, Kaysville, UT, USA) based on the previous research data from our pilot study. 125 patients was calculated to detect a 0.75 value of the area under the curve (AUC) (receiver operating characteristic [ROC] curve, calculated for the SPI to predict moderate-to-severe pain) with an alpha error of 5% and a power of 90%. Considering a dropout rate of 15%, the final sample size of 150 patients was needed. All the data were analyzed by using IBM SPSS 26.0 statistical software (SPSS, Chicago, IL, USA). Continuous data are presented as the mean ± SD, or median with the interquartile range [IQR] according to the normality of the distribution. Categorical variables are presented as category counts and percentages. ROC curves were analyzed, the associated AUC and the sensitivity, the specificity were computed to examine the ability of SPI to predict postoperative moderate-to-severe pain. The maximum value of Youden’s index (the highest combined sensitivity and specificity) was regarded as the best cut-off value of the variable of the ROC curve. The asymptotic 95% CI of each AUC was calculated. A two-tailed P level less than 0.05 (P < 0.05) was considered statistically significant. Results Patient characteristics One hundred and fifty patients undergoing adenotonsillectomy surgery were enrolled in this study. Four patients were excluded due to cancellation of surgery, five patients were excluded because of protocol violation during the study, five other patients were excluded due to intraoperative use of atropine and another four patients was excluded because of laryngeal spasm after extubation. Finally, one hundred and thirty-two patients were included and analyzed in the study (Fig. 1 ). Demographic data, including age, sex, weight, height, body mass index, duration of surgical procedure and duration of anesthesia were obtained. Patients and clinical characteristics were presented in Table 1 . Table 1 Patients and clinical characteristics (n = 132) Variable Age (months) 69(53,87) Gender(Male/Female) 73/59 Weight (kg) 23.4(18.6,30.2) Height (cm) 122(109,138) BMI (kg/m 2 ) 15.9 ± 2.8 Duration of surgical procedure (min) 39(30,59) Duration of anesthesia (min) 58(48,81) NOTE. Data are presented as mean ± standard deviation or median with interquartile range. Abbreviations: BMI = body mass index. Predictive power of SPI for early postoperative pain The SPI max , MAP max and HR max of the patients whose CHEOPS scores less than 4 were 43 ± 6, 58 ± 9mmHg and 90 ± 12 beat/min while of the patients whose CHEOPS scores equal or greater than 4 were 54 ± 8, 67 ± 11mmHg and 96 ± 13 beat/min respectively(Table 2 ). According to ROCs, the SPI had a good predictive accuracy (AUC: 0.84, 95% CI: 0.74–0.92, P < 0.001) for postoperative moderate-to-severe pain compared with MAP (AUC: 0.53, 95% CI: 0.41–0.67, P = 0.58) and HR (AUC: 0.62, 95% CI: 0.46–0.76, P = 0.19) (Table 2 , Fig. 2 ). The best-fit (the highest combined sensitivity and specificity) cut-off values of SPI was 46 with the sensitivity of 79.4% and specificity of 87.8% to distinguish mild pain from moderate-to-severe pain after surgery. (Table 2 ). Table 2 Predictive power of surgical pleth index for early postoperative pain CHEOPS (0–3) CHEOPS (≥ 4) Cutoff value Sensitivity (%) Specificity (%) AUC (95% CI) P value SPI max 43 ± 6 54 ± 8 46 79.4 87.8 0.84(0.74–0.92) < 0.001 MAP max (mmHg) 58 ± 9 67 ± 11 / / / 0.53(0.41–0.67) 0.58 HR max (beat/min) 90 ± 12 96 ± 13 / / / 0.62(0.46–0.76) 0.19 Abbreviations: SPI max =the maximum value of surgical pleth index; MAP max =the maximum value of mean arterial pressure; HR max =the maximum value of Heart rate; CHEOPS = Children’s Hospital of Eastern Ontario Pain Scale; AUC = area under curve. Discussion In this study, we found that SPI can effectively predict the occurrence of early moderate-to-severe pain for the children admitted to PACU after adenotonsillectomy surgery under general anesthesia while neither MAP nor HR can predict the occurrence of moderate-to-severe pain. The present study indicated that SPI can better predict and evaluate early postoperative pain in pediatric patients than traditional monitoring variables such as MAP and HR. Several studies have also shown that SPI guiding the administration of opioids may be beneficial and SPI was superior to MAP and HR in detecting nociceptive events. Chen et al. used SPI-guided analgesia in the adult patients undergoing elective ear-nose-throat surgery, resulting in less remifentanil consumption, more stable hemodynamics, lower incidence of adverse events, and comparable anesthesia recovery times when compared with standard clinical analgesia practice[ 17 ]. They also found that SPI performed better in detecting the balance between nociception and antinociception than BIS, MAP, and HR. GRUENEWALD et al. evaluated the nociception-antinociception balance using SPI and Analgesia Nociception Index (ANI) in twenty-four adult patients scheduled for non-emergency surgery during sevoflurane-induced anesthesia and a stepwise increase of remifentanil effect site concentration[ 18 ]. They eventually concluded that both SPI and ANI were more suitable for detecting nociceptive events and inadequate analgesia than standard monitoring variables such as BIS, HR and MAP. Thee et al. investigated the correlation between SPI and pain intensity in 100 adult patients undergoing elective surgery under general anesthesia[ 19 ]. In their study, SPI was moderately correlated with the Numerical Rating Scale (NRS) while MAP and HR showed no significant correlation with NRS. The ROC curve showed moderate sensitivity and specificity of SPI in discriminating between low and moderate, and between moderate and severe pain. Park et al. carried out one research on intraoperative analgesic requirements by comparing SPI-guided analgesia with traditional analgesia practices (MAP and HR) in pediatric patients undergoing adenotonsillectomy under general anesthesia[ 20 ]. Their research suggested that SPI-guided analgesia reduced fentanyl consumption during the surgery compared with conventional analgesia practices. Harju et al. tested the performance of SPI in detecting nociception at the time of intubation, surgical incision, and at signs of insufficient anti-nociception in children younger than 24 months[ 21 ]. Their study indicated that an increase in SPI was associated with the clinical decision to administer fentanyl in infants, and the SPI had potential to detect nociception in small children. However, the duration of response was very short and there were significant inter-individual differences among children, which might have interfered with clinical application of the SPI in pediatric patients. The present study showed that the best cutoff of SPI = 46 had a sensitivity of 79.4% and a specificity of 87.8% to discriminate between patients with CHEOPS less than 4 points (no or mild pain) and CHEOPS equal or greater than 4 points (moderate or severe pain). This study is almost consistent with the conclusion of Ledowski et al. relevant study[ 22 ]. In their study, 93 children aged 2 to 16 years scheduled for elective surgery under general anesthesia with sevoflurane and opioids were analyzed to determine a appropriate target of SPI to predict moderate-severe postoperative pain. The SPI was directly recorded before the end of surgery and compared with acute postoperative pain (different pain scale scores were adopted for children of different ages among 2–3 years, 4–8 years and 9–16 years old) in the PACU. Their study showed that the optimal cutoff value of SPI to predict moderate-severe postoperative pain was 40 with the highest combined sensitivity (76%) and specificity (62%), and slightly higher values in younger children (2–3 years) vs older (9–16 years) children. Their research also indicated that there was a significant negative correlation between the SPI and the age in children with moderate-severe pain in PACU. That might be related to the different heart rates of pediatric patients at different ages. According to the formula of SPI = 100-(0.7×PPGAnorm + 0.3×HBInorm), the SPI is influenced predominantly by two factors PPGAnorm and HBInorm. Firstly, the amplitude of the plethysmographic pulse wave depends on autonomic tone and especially on sympathetic nerve drive, which in turn may depend on emotions of the individual such as fear, excitement or personal discomfort[ 19 ]. Secondly, the heartbeat interval (HBI) may be affected by pacemakers or drugs such as atropine. Heart rates after atropine were 59% higher than normal heart rates in adults, and the HBI was 63% of the normal heart rate after using atropine, which was 4% lower than the baseline HBI[ 23 ]. Therefore, considered that intravenous injection of atropine may affect HBI, we excluded the patients who received atropine during the operation in this study. In another study, Ledowski et al. investigated the use of SPI to predict postoperative pain in two hundred adult patients who underwent non-emergency surgery[ 24 ]. They concluded that the best cut-off value of SPI = 30 measured at the end of the surgery predicted moderate-to-severe postoperative pain in adult patients, which was significantly lower than that in pediatric patients. That might be because the basal heart rate of children was higher than that of adults, resulting in a higher baseline value of SPI in pediatric patients. There were several limitations in the present study. First, since the assessment of postoperative pain in children is naturally a challenge, it is conceivable that postoperative emergence agitation in some pediatric patients may have confounded the rating of postoperative pain and the predictive value of SPI. Second, only pediatric patients aged 4–8 years old were included in this study, our results could not be extended to patients younger than 4 years or older than 8 years. It is necessary to further explore the relationship between the SPI and the age. In addition, this study was a single-center study in a specific pediatric population (patients undergoing adenotonsillectomy surgery). A larger and multicenter study is needed to clarify and generalize these findings. Conclusion In conclusion, SPI can effectively predict the occurrence of early postoperative moderate-to-severe pain in pediatric patients undergoing adenotonsillectomy surgery under general anesthesia. SPI might be one reliable pain assessment tool to guide pediatric anesthesiologists for timely identification and management of postoperative pain. The SPI may also provide certain references for pediatric anesthesiologists to implement precise anesthesia during the perioperative period. Declarations Authors’ contributions Weizhi Zhang designed the study；Lin Li and Qinghua Meng collected the data and analyzed the data for the study; Lin Li prepared the manuscript. All authors contributed to the article and approved the submitted version. Financial Support Shanxi Province Natural Science Foundation Project (202203021221290) Conflicts of Interest The authors declare that they have no conflicts of interest. Ethics approval and consent to participate Ethics approval for this trial was obtained from Institutional Ethics Committee of Shanxi Provincial Children’s Hospital (reference number：IRB-KYYN-2021-002, 6 May 2021) and conducted following the Declaration of Helsinki. 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Cite Share Download PDF Status: Published Journal Publication published 31 Oct, 2025 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 01 Aug, 2025 Reviews received at journal 15 Jul, 2025 Reviewers agreed at journal 07 Jul, 2025 Reviews received at journal 25 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviewers invited by journal 23 Jun, 2025 Editor assigned by journal 18 Jun, 2025 Editor invited by journal 27 May, 2025 Submission checks completed at journal 21 May, 2025 First submitted to journal 21 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6565979","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":475962665,"identity":"ddd0e6bd-6c16-441c-9bfd-85af8087d99d","order_by":0,"name":"Lin Li","email":"","orcid":"","institution":"Shanxi Provincial Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Li","suffix":""},{"id":475962666,"identity":"b492e22e-974c-4f5f-b1f0-0712573d5cee","order_by":1,"name":"Qinghua Meng","email":"","orcid":"","institution":"Shanxi Provincial Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qinghua","middleName":"","lastName":"Meng","suffix":""},{"id":475962667,"identity":"82b93221-c181-4a6e-889e-c5afe3eef8e5","order_by":2,"name":"Weizhi Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIie3QMQrCMBTG8VcKD4en2aTQIVeouDgoXiWlg0sHD+AguEZcI14iR4gE6qIncBEKzhUXhw4qiKONm2B+8/fnkQB43u9CAAqNqW7fJZhu1/KrQ0R920KHIVeT8kp1hzO5rywQcNY1n5NACdEnwp46LLWdDqC33ojPSRgLk+URBpq1tVUEIjk2JBinc5snONaMTpbQIaE4Cxa5wFS3JbglET+HYW0wU/sieXxy1PwWLnflRdXFaCWzsqpuQ87ihuSleF91mj/NnJee53l/6A7qa0GoMD3YKgAAAABJRU5ErkJggg==","orcid":"","institution":"Shanxi Provincial Children’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Weizhi","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-04-30 14:38:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6565979/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6565979/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-025-03415-1","type":"published","date":"2025-10-31T15:58:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85616999,"identity":"9f4b829c-c96d-4b38-93bc-41e04a1ead6b","added_by":"auto","created_at":"2025-06-29 14:41:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":219409,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flowchart.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6565979/v1/4836eae61956e0308dc0c94c.png"},{"id":85615902,"identity":"0187a2a8-5458-4986-ac4c-6378ad12ef3a","added_by":"auto","created_at":"2025-06-29 14:33:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":165178,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves of the SPImax, MAPmax and HRmax for prediction of early postoperative pain.\u003c/p\u003e\n\u003cp\u003eAbbreviations: SPImax,the maximum of surgical pleth index; MAPmax, the maximum of mean arterial pressure; HRmax, the maximum of heart rates.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6565979/v1/34ee819bef5cbf1f4dd2aa80.png"},{"id":95040683,"identity":"6d6803a5-b147-44d1-8e61-b2c07c485e25","added_by":"auto","created_at":"2025-11-03 16:10:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":833735,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6565979/v1/a59d4e77-c13e-45f2-94ac-34848eca989e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive value of surgical pleth index for early postoperative pain in children undergoing general anesthesia: A prospective observational study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePostoperative pain is common in children during early recovering from general anesthesia, especially for pediatric patients undergoing adenotonsillectomy surgery[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It is crucial to be able to assess postoperative pain in a timely and effective manner, because discomfort and other adverse events such as emergence agitation will be greatly reduced when postoperative pain is identified and treated as early as possible[\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, it is full of challenges to predict postoperative pain and deal with it in advance due to lack of reliable pain assessment methods and tools, especially for pediatric patients during early recovery from general anesthesia.\u003c/p\u003e \u003cp\u003eAt present, the administration of analgesics during surgery still relies on traditional methods based on changes in blood pressure and heart rate[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. There have been no effective tools that can precisely monitor the depth of intraoperative analgesia and accurately predict the occurrence of postoperative pain. The surgical pleth index (SPI), first introduced in 2007, an index based on changes related to the balance between the sympathetic and parasympathetic nervous systems, has been used for assessment of nociception-antinociception balance[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. SPI is a dimensionless, normalized score (0-100) which is based on an algorithm combining the pulse photoplethysmographic amplitude (PPGA) and the normalised heart beat interval (HBI), both obtained from pulse oximetry monitoring (GE Healthcare, Helsinki, Finland )[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecently, the SPI has been used to monitor the surgical stress response and guide appropriate analgesic administration during general anesthesia[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. It is related to surgical stimuli and the dosage of analgesics, and predicts the effect of pain stimulation and analgesic treatment more accurately than general clinical parameters[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. An increasing number of studies have shown that SPI has the potential to reflect intraoperative noxious stimuli and guide the management of opioids in adult patients[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The evidence of SPI in guiding intraoperative analgesia and predicting postoperative pain in pediatric patients is scarce. The primary aim of this study was to evaluate the value of surgical pleth index to predict early postoperative pain in pediatric patients undergoing adenotonsillectomy surgery under general anesthesia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and Patients\u003c/h2\u003e \u003cp\u003eThis was a prospective observational study conducted at Shanxi Provincial Children\u0026rsquo;s Hospital from October 2022 to May 2024. This study was approved by the Institutional Ethics Committee of Shanxi Provincial Children\u0026rsquo;s Hospital and registered on the Chinese Clinical Trials Registry (ChiCTR2200058658, April 13, 2022). Written informed consent was obtained from parents or legal guardians the day before data collection and surgery.\u003c/p\u003e \u003cp\u003eOne hundred and fifty patients aged 4\u0026ndash;8 years, ASA physical status I or II, scheduled to undergo adenotonsillectomy surgery were enrolled in the clinical trial. Patients with a history of neurological or psychiatric disorders, cardiac arrhythmia, preoperative chronic pain, or a history of upper respiratory tract infection in the preceding 4 weeks were excluded. Patients who had recently used analgesic or sedative drugs, had a history of adverse reactions or allergies to anesthetic drugs, or had a history of abnormal anesthesia were also excluded from the study. The flow chart of this study is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnesthetic technique\u003c/h3\u003e\n\u003cp\u003eAll patients were given intramuscular injection of atropine 0.01mg/kg 30 min before surgery. After entrance to the operating room, noninvasive blood pressure (NIBP), electrocardiography (ECG), and pulse oximetry saturation (SpO\u003csub\u003e2\u003c/sub\u003e) were monitored for each patient. General anesthesia was performed by the same pediatric anesthesiologist. Anesthesia induction was conducted by intravenous injection of sufentanil 0.4ug/kg, etomidate 0.3mg/kg and cisatracurium 0.15mg/kg sequentially. After spontaneous respiration disappeared, then intraoral endotracheal intubation was performed using video laryngoscope, and pressure-controlled ventilation mode (Drager Fabius GS premium, Germany) was executed. The fraction of inspired oxygen was 50%, and the inspiratory to expiratory ratio was 1:1.5. By adjusting the inspiration pressure and frequency, the end-tidal carbon dioxide partial pressure was maintained between 35 mmHg and 45 mmHg (1 mmHg\u0026thinsp;=\u0026thinsp;0.133 kPa). General anesthesia was maintained by continuous infusion of propofol 6\u0026ndash;10 mg/kg/h and remifentanil 0.3\u0026ndash;0.5\u0026micro;g/kg/min. Parecoxib sodium 0.1mg/kg was given intravenously immediately at the beginning of surgery for each patient in order to achieve the effect of preemptive analgesia. The infusion of anesthetic drugs was stopped 5min before the end of surgery.\u003c/p\u003e\n\u003ch3\u003eSurgical pleth index monitoring\u003c/h3\u003e\n\u003cp\u003eSurgical pleth index (SPI) monitoring for each patient was performed from the same shared SpO\u003csub\u003e2\u003c/sub\u003e measurement finger which was on the side opposite to the NIBP measurement through the CARESCAPE Monitor B650 (GE Healthcare, Helsinki, Finland). The plethysmographic waveform was continuously recorded and reanalyzed to produce the normalized pulse plethysmographic amplitude (PPGAnorm), and the normalized heartbeat interval (HBInorm). SPI was computed as a combination of PPGAnorm and HBInorm: SPI\u0026thinsp;=\u0026thinsp;100-(0.7\u0026times;PPGAnorm\u0026thinsp;+\u0026thinsp;0.3\u0026times;HBInorm)[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The Monitor B650 displayed the SPI values between 0 and 100 directly. The SPI values, mean arterial pressure (MAP) and the heart rate (HR) were recorded at each minute for five minutes immediately after surgery. The maximum values of SPI, MAP and HR (SPI\u003csub\u003emax\u003c/sub\u003e, MAP\u003csub\u003emax\u003c/sub\u003e and HR\u003csub\u003emax\u003c/sub\u003e respectively) were taken for analysis.\u003c/p\u003e\n\u003ch3\u003eEvaluation of early postoperative pain\u003c/h3\u003e\n\u003cp\u003eAll patients were sent to the postanesthesia care unit (PACU) for further observation after surgery and extubation. In the PACU, pain score was performed each 10min for a total of 3 times (10min, 20min and 30min after admission to PACU, the maximum score was taken for analysis). The pain score was determined using the modified Children\u0026rsquo;s Hospital of Eastern Ontario Pain Scale (CHEOPS), which comprises five items including crying, facial, verbal, torso, and leg status that were summed to calculate a final pain score (range: 0\u0026ndash;10)[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The final score of 0\u0026ndash;3 is classified as no or mild pain, 4\u0026ndash;6 as moderate pain, and 7\u0026ndash;10 as severe pain. Children with moderate to severe pain (score\u0026thinsp;\u0026ge;\u0026thinsp;4 points) were treated with intravenous injection of sufentanil at 0.1ug/kg as a remedy.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe sample size was calculated using PASS software (version 15.0, NCSS statistical software, Kaysville, UT, USA) based on the previous research data from our pilot study. 125 patients was calculated to detect a 0.75 value of the area under the curve (AUC) (receiver operating characteristic [ROC] curve, calculated for the SPI to predict moderate-to-severe pain) with an alpha error of 5% and a power of 90%. Considering a dropout rate of 15%, the final sample size of 150 patients was needed.\u003c/p\u003e \u003cp\u003eAll the data were analyzed by using IBM SPSS 26.0 statistical software (SPSS, Chicago, IL, USA). Continuous data are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, or median with the interquartile range [IQR] according to the normality of the distribution. Categorical variables are presented as category counts and percentages. ROC curves were analyzed, the associated AUC and the sensitivity, the specificity were computed to examine the ability of SPI to predict postoperative moderate-to-severe pain. The maximum value of Youden\u0026rsquo;s index (the highest combined sensitivity and specificity) was regarded as the best cut-off value of the variable of the ROC curve. The asymptotic 95% CI of each AUC was calculated. A two-tailed P level less than 0.05 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient characteristics\u003c/h2\u003e\n \u003cp\u003eOne hundred and fifty patients undergoing adenotonsillectomy surgery were enrolled in this study. Four patients were excluded due to cancellation of surgery, five patients were excluded because of protocol violation during the study, five other patients were excluded due to intraoperative use of atropine and another four patients was excluded because of laryngeal spasm after extubation. Finally, one hundred and thirty-two patients were included and analyzed in the study (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Demographic data, including age, sex, weight, height, body mass index, duration of surgical procedure and duration of anesthesia were obtained. Patients and clinical characteristics were presented in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePatients and clinical characteristics (n\u0026thinsp;=\u0026thinsp;132)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69(53,87)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender(Male/Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73/59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.4(18.6,30.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeight (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e122(109,138)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDuration of surgical procedure (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(30,59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDuration of anesthesia (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58(48,81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eNOTE. Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median with interquartile range.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eAbbreviations: BMI\u0026thinsp;=\u0026thinsp;body mass index.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003ePredictive power of SPI for early postoperative pain\u003c/h3\u003e\n\u003cp\u003eThe SPI\u003csub\u003emax\u003c/sub\u003e, MAP\u003csub\u003emax\u003c/sub\u003e and HR\u003csub\u003emax\u003c/sub\u003e of the patients whose CHEOPS scores less than 4 were 43\u0026thinsp;\u0026plusmn;\u0026thinsp;6, 58\u0026thinsp;\u0026plusmn;\u0026thinsp;9mmHg and 90\u0026thinsp;\u0026plusmn;\u0026thinsp;12 beat/min while of the patients whose CHEOPS scores equal or greater than 4 were 54\u0026thinsp;\u0026plusmn;\u0026thinsp;8, 67\u0026thinsp;\u0026plusmn;\u0026thinsp;11mmHg and 96\u0026thinsp;\u0026plusmn;\u0026thinsp;13 beat/min respectively(Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). According to ROCs, the SPI had a good predictive accuracy (AUC: 0.84, 95% CI: 0.74\u0026ndash;0.92, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for postoperative moderate-to-severe pain compared with MAP (AUC: 0.53, 95% CI: 0.41\u0026ndash;0.67, P\u0026thinsp;=\u0026thinsp;0.58) and HR (AUC: 0.62, 95% CI: 0.46\u0026ndash;0.76, P\u0026thinsp;=\u0026thinsp;0.19) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The best-fit (the highest combined sensitivity and specificity) cut-off values of SPI was 46 with the sensitivity of 79.4% and specificity of 87.8% to distinguish mild pain from moderate-to-severe pain after surgery. (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\" style=\"margin-right: calc(1%); width: 99%;\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePredictive power of surgical pleth index for early postoperative pain\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 3.9103%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003eCHEOPS\u003c/p\u003e\n \u003cp\u003e(0\u0026ndash;3)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003eCHEOPS\u003c/p\u003e\n \u003cp\u003e(\u0026ge;\u0026thinsp;4)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 3.024%;\"\u003e\n \u003cp\u003eCutoff value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003eSensitivity\u003c/p\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003eSpecificity\u003c/p\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 4.3796%;\"\u003e\n \u003cp\u003eAUC (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 2.2941%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 3.9103%;\"\u003e\n \u003cp\u003eSPI\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003e43\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003e54\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 3.024%;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003e79.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003e87.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.3796%;\"\u003e\n \u003cp\u003e0.84(0.74\u0026ndash;0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 2.2941%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 3.9103%;\"\u003e\n \u003cp\u003eMAP\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003e58\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003e67\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 3.024%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.3796%;\"\u003e\n \u003cp\u003e0.53(0.41\u0026ndash;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 2.2941%;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 3.9103%;\"\u003e\n \u003cp\u003eHR\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e(beat/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003e90\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 3.8582%;\"\u003e\n \u003cp\u003e96\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 3.024%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.171%;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 4.3796%;\"\u003e\n \u003cp\u003e0.62(0.46\u0026ndash;0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 2.2941%;\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 30.0834%;\"\u003eAbbreviations: SPI\u003csub\u003emax\u003c/sub\u003e=the maximum value of surgical pleth index; MAP\u003csub\u003emax\u003c/sub\u003e=the maximum value of mean arterial pressure; HR\u003csub\u003emax\u003c/sub\u003e=the maximum value of Heart rate; CHEOPS\u0026thinsp;=\u0026thinsp;Children\u0026rsquo;s Hospital of Eastern Ontario Pain Scale; AUC\u0026thinsp;=\u0026thinsp;area under curve.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we found that SPI can effectively predict the occurrence of early moderate-to-severe pain for the children admitted to PACU after adenotonsillectomy surgery under general anesthesia while neither MAP nor HR can predict the occurrence of moderate-to-severe pain. The present study indicated that SPI can better predict and evaluate early postoperative pain in pediatric patients than traditional monitoring variables such as MAP and HR. Several studies have also shown that SPI guiding the administration of opioids may be beneficial and SPI was superior to MAP and HR in detecting nociceptive events. Chen et al. used SPI-guided analgesia in the adult patients undergoing elective ear-nose-throat surgery, resulting in less remifentanil consumption, more stable hemodynamics, lower incidence of adverse events, and comparable anesthesia recovery times when compared with standard clinical analgesia practice[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. They also found that SPI performed better in detecting the balance between nociception and antinociception than BIS, MAP, and HR. GRUENEWALD et al. evaluated the nociception-antinociception balance using SPI and Analgesia Nociception Index (ANI)\u003c/p\u003e \u003cp\u003ein twenty-four adult patients scheduled for non-emergency surgery during sevoflurane-induced anesthesia and a stepwise increase of remifentanil effect site concentration[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. They eventually concluded that both SPI and ANI were more suitable for detecting nociceptive events and inadequate analgesia than standard monitoring variables such as BIS, HR and MAP. Thee et al. investigated the correlation between SPI and pain intensity in 100 adult patients undergoing elective surgery under general anesthesia[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In their study, SPI was moderately correlated with the Numerical Rating Scale (NRS) while MAP and HR showed no significant correlation with NRS. The ROC curve showed moderate sensitivity and specificity of SPI in discriminating between low and moderate, and between moderate and severe pain. Park et al. carried out one research on intraoperative analgesic requirements by comparing SPI-guided analgesia with traditional analgesia practices (MAP and HR) in pediatric patients undergoing adenotonsillectomy under general anesthesia[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Their research suggested that SPI-guided analgesia reduced fentanyl consumption during the surgery compared with conventional analgesia practices. Harju et al. tested the performance of SPI in detecting nociception at the time of intubation, surgical incision, and at signs of insufficient anti-nociception in children younger than 24 months[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Their study indicated that an increase in SPI was associated with the clinical decision to administer fentanyl in infants, and the SPI had potential to detect nociception in small children. However, the duration of response was very short and there were significant inter-individual differences among children, which might have interfered with clinical application of the SPI in pediatric patients.\u003c/p\u003e \u003cp\u003eThe present study showed that the best cutoff of SPI\u0026thinsp;=\u0026thinsp;46 had a sensitivity of 79.4% and a specificity of 87.8% to discriminate between patients with CHEOPS less than 4 points (no or mild pain) and CHEOPS equal or greater than 4 points (moderate or severe pain). This study is almost consistent with the conclusion of Ledowski et al. relevant study[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In their study, 93 children aged 2 to 16 years scheduled for elective surgery under general anesthesia with sevoflurane and opioids were analyzed to determine a appropriate target of SPI to predict moderate-severe postoperative pain. The SPI was directly recorded before the end of surgery and compared with acute postoperative pain (different pain scale scores were adopted for children of different ages among 2\u0026ndash;3 years, 4\u0026ndash;8 years and 9\u0026ndash;16 years old) in the PACU. Their study showed that the optimal cutoff value of SPI to predict moderate-severe postoperative pain was 40 with the highest combined sensitivity (76%) and specificity (62%), and slightly higher values in younger children (2\u0026ndash;3 years) vs older (9\u0026ndash;16 years) children. Their research also indicated that there was a significant negative correlation between the SPI and the age in children with moderate-severe pain in PACU. That might be related to the different heart rates of pediatric patients at different ages. According to the formula of SPI\u0026thinsp;=\u0026thinsp;100-(0.7\u0026times;PPGAnorm\u0026thinsp;+\u0026thinsp;0.3\u0026times;HBInorm), the SPI is influenced predominantly by two factors PPGAnorm and HBInorm. Firstly, the amplitude of the plethysmographic pulse wave depends on autonomic tone and especially on sympathetic nerve drive, which in turn may depend on emotions of the individual such as fear, excitement or personal discomfort[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Secondly, the heartbeat interval (HBI) may be affected by pacemakers or drugs such as atropine. Heart rates after atropine were 59% higher than normal heart rates in adults, and the HBI was 63% of the normal heart rate after using atropine, which was 4% lower than the baseline HBI[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Therefore, considered that intravenous injection of atropine may affect HBI, we excluded the patients who received atropine during the operation in this study. In another study, Ledowski et al. investigated the use of SPI to predict postoperative pain in two hundred adult patients who underwent non-emergency surgery[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. They concluded that the best cut-off value of SPI\u0026thinsp;=\u0026thinsp;30 measured at the end of the surgery predicted moderate-to-severe postoperative pain in adult patients, which was significantly lower than that in pediatric patients. That might be because the basal heart rate of children was higher than that of adults, resulting in a higher baseline value of SPI in pediatric patients.\u003c/p\u003e \u003cp\u003eThere were several limitations in the present study. First, since the assessment of postoperative pain in children is naturally a challenge, it is conceivable that postoperative emergence agitation in some pediatric patients may have confounded the rating of postoperative pain and the predictive value of SPI. Second, only pediatric patients aged 4\u0026ndash;8 years old were included in this study, our results could not be extended to patients younger than 4 years or older than 8 years. It is necessary to further explore the relationship between the SPI and the age. In addition, this study was a single-center study in a specific pediatric population (patients undergoing adenotonsillectomy surgery). A larger and multicenter study is needed to clarify and generalize these findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, SPI can effectively predict the occurrence of early postoperative moderate-to-severe pain in pediatric patients undergoing adenotonsillectomy surgery under general anesthesia. SPI might be one reliable pain assessment tool to guide pediatric anesthesiologists for timely identification and management of postoperative pain. The SPI may also provide certain references for pediatric anesthesiologists to implement precise anesthesia during the perioperative period.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWeizhi Zhang designed the study；Lin Li and Qinghua Meng collected the data and analyzed the data for the study; Lin Li prepared the manuscript. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Support\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShanxi Province Natural Science Foundation Project (202203021221290)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval for this trial was obtained from Institutional Ethics Committee of Shanxi Provincial Children\u0026rsquo;s Hospital (reference number：IRB-KYYN-2021-002, 6 May 2021) and conducted following the Declaration of Helsinki. \u0026nbsp;Written informed consent was obtained from the parents or legal guardians for all participant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLin C, Abboud S, Zoghbi V, Kasimova k, Thein J, Meister KD, Sidell DR, Balakrishnan K, Tsui BCH. 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Eur J Anaesthesiol. 2015;32(1):44\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark JH, Lim BG, Kim H, Lee IO, Kong MH, Kim NS. Comparison of Surgical Pleth Index-guided Analgesia with Conventional Analgesia Practices in Children: A Randomized Controlled Trial. Anesthesiology. 2015;122(6):1280\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarju J, Kalliom\u0026auml;ki ML, Leppikangas H, Kiviharju M, Yli-Hankala A. Surgical pleth index in children younger than 24 months of age: a randomized double-blinded trial. Br J Anaesth. 2016;117(3):358\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLedowski T, Sommerfield D, Slevin L, Conrad J, Ungern-Sternberg BS. Surgical pleth index: prediction of postoperative pain in children? Br J Anaesth. 2017;119(5):979\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH\u0026ouml;cker J, Broch O, Gr\u0026auml;sner JT, Gruenewald M, Ilies C, Steinfath M, Bein B. Surgical stress index in response to pacemaker stimulation or atropine. Br J Anaesth. 2010;105(2):150\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLedowski T, Schneider M, Gruenewald M, Goyal RK, Teo SR, Hruby J. Surgical pleth index: prospective validation of the score to predict moderate-to-severe postoperative pain. Br J Anaesth. 2019;123(2):e328\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Surgical pleth index, postoperative pain, children, general anesthesia, adenotonsillectomy surgery","lastPublishedDoi":"10.21203/rs.3.rs-6565979/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6565979/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePostoperative pain is common in children during early recovering from general anesthesia, especially for pediatric patients undergoing adenotonsillectomy surgery. There is no valid tool to predict postoperative pain at present.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eOne hundred and fifty patients aged 4–8 years, scheduled to undergo adenotonsillectomy surgery were enrolled in the clinical trial. All patients were given intravenous general anesthesia and endotracheal intubation by the same pediatric anesthesiologist. Surgical pleth index (SPI) monitoring for each patient was performed from the same shared SpO\u003csub\u003e2\u003c/sub\u003e measurement finger which was on the side opposite to the NIBP measurement through the CARESCAPE Monitor B650 (GE Healthcare, Helsinki, Finland). The SPI values, mean arterial pressure (MAP) and heart rate (HR) were recorded at each minute for five minutes immediately after surgery. The maximum values of SPI, MAP and HR (SPI\u003csub\u003emax\u003c/sub\u003e, MAP\u003csub\u003emax\u003c/sub\u003e and HR\u003csub\u003emax\u003c/sub\u003e respectively) were taken for analysis. Early postoperative pain was assessed for each patient using the modified Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) in postanesthesia care unit (PACU). Receiver-operating characteristics (ROC) curves and the associated areas under the curves (AUC) were computed to analyze the ability of SPI to predict early postoperative pain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e One hundred and thirty-two patients were included and analyzed finally. The SPI\u003csub\u003emax\u003c/sub\u003e, MAP\u003csub\u003emax\u003c/sub\u003e and HR\u003csub\u003emax\u003c/sub\u003e of the patients whose CHEOPS scores less than 4 were 43±6, 58±9mmHg and 90±12 beat/min while of the patients whose CHEOPS scores equal or greater than 4 were 54±8, 67±11mmHg and 96±13 beat/min respectively. The SPI (AUC: 0.84, 95% CI: 0.74-0.92, P\u0026lt;0.001) had a good predictive value for postoperative moderate-to-severe pain compared with MAP (AUC: 0.53, 95% CI: 0.41-0.67, P=0.58) and HR (AUC: 0.62, 95% CI: 0.46-0.76, P=0.19). The best-fit (highest combined sensitivity and specificity ) cut-off values of SPI to distinguish mild pain from moderate-to-severe pain was 46 with the sensitivity of 79.4% and specificity of 87.8%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e SPI can effectively predict the occurrence of early postoperative moderate-to-severe pain in pediatric patients undergoing adenotonsillectomy surgery under general anesthesia. SPI might be one reliable pain assessment tool to guide pediatric anesthesiologists for timely identification and management of postoperative pain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration: \u003c/strong\u003eChinese Clinical Trial Registry, identifier: ChiCTR2200058658 (13/04/2022).\u003c/p\u003e","manuscriptTitle":"Predictive value of surgical pleth index for early postoperative pain in children undergoing general anesthesia: A prospective observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-29 14:33:05","doi":"10.21203/rs.3.rs-6565979/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-01T17:36:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-15T16:07:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336785851226526042539686068311786610885","date":"2025-07-07T23:49:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-25T18:22:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97058402910200960950113582109637500833","date":"2025-06-24T21:46:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-23T12:51:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-18T05:47:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-27T11:35:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-21T08:48:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2025-05-21T08:47:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0925b149-22a6-405b-80aa-22cd6bcd7cb3","owner":[],"postedDate":"June 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:07:45+00:00","versionOfRecord":{"articleIdentity":"rs-6565979","link":"https://doi.org/10.1186/s12871-025-03415-1","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2025-10-31 15:58:30","publishedOnDateReadable":"October 31st, 2025"},"versionCreatedAt":"2025-06-29 14:33:05","video":"","vorDoi":"10.1186/s12871-025-03415-1","vorDoiUrl":"https://doi.org/10.1186/s12871-025-03415-1","workflowStages":[]},"version":"v1","identity":"rs-6565979","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6565979","identity":"rs-6565979","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}