OBJECTIVE: The objective of this study was to determine whether combined total intravenous anesthesia (TIVA) technique with propofol/remifentanil is associated with less SSEP suppression when compared to combined volatile agent desflurane/remifentanil anesthesia during corrective scoliosis surgery at a comparable depth of anesthesia.
DESIGN: It is a randomized controlled trial.
SETTING: The study was conducted at the Single tertiary University Hospital during October 2014 to June 2015.
PATIENTS: Patients who required SSEP and had no neurological deficits, and were of American Society of Anesthesiologist I and II physical status, were included. Patients who had sensory or motor deficits preoperatively and significant cardiovascular and respiratory disease were excluded. A total of 72 patients were screened, and 67 patients were randomized and allocated to two groups: 34 in desflurane/remifentanil group and 33 in TIVA group. Four patients from desflurane/remifentanil group and three from TIVA group were withdrawn due to decrease in SSEP amplitude to <0.3 µV after induction of anesthesia. Thirty patients from each group were analyzed.
INTERVENTIONS: Sixty-seven patients were randomized to receive TIVA or desflurane/remifentanil anesthesia.
MAIN OUTCOME MEASURES: The measurements taken were the amplitude and latency of SSEP monitoring at five different time points during surgery: before and after the induction of anesthesia, at skin incision, at pedicle screw insertion, and at rod insertion.
RESULTS: Both anesthesia techniques, TIVA and desflurane/remifentanil, resulted in decreased amplitude and increased latencies of both cervical and cortical peaks. The desflurane/remifentanil group had a significantly greater reduction in the amplitude ( p = 0.004) and an increase in latency ( p = 0.002) of P40 compared with the TIVA group. However, there were no differences in both amplitude ( p = 0.214) and latency ( p = 0.16) in cervical SSEP between the two groups.
CONCLUSIONS: Compared with TIVA technique, desflurane/remifentanil anesthesia caused more suppression in cortical SSEP, but not in cervical SSEP, at a comparable depth of anesthesia.
PURPOSE: To investigate the prevalence and the associated risk factors of chronic neuropathic pain symptoms using painDETECT questionnaire in adolescent idiopathic scoliosis (AIS) patients who underwent posterior spinal fusion (PSF) surgery.
OVERVIEW OF LITERATURE: Post-lumbar surgery syndrome is a disease entity that describes neuropathic pain following spinal surgery. However, few studies have investigated the prevalence and risk factors for neuropathic pain in pediatric population undergoing corrective spinal surgery.
METHODS: Forty AIS patients were recruited. Demographic, preoperative, and postoperative data were recorded. The magnitude and characteristics of postoperative pain were assessed using the painDETECT questionnaire through telephone enquiries at intervals of 2, 6, 12, and 24 weeks. Statistical analyses were followed by Pearson correlation test to determine the relationship between pain scores at 6, 12, and 24 weeks with the risk factors.
RESULTS: Based on the painDETECT questionnaire, 90% of the patients had nociceptive pain, and 10% had a possible neuropathic pain component at 2 weeks postoperatively as per a mean painDETECT score of 7.1±4.5. Assessments at 6, 12, and 24 weeks showed that no patients had neuropathic pain with painDETECT scores of 4.4±3.2, 2.9±2.9, and 1.5±2.0, respectively. There was a significant correlation between total postoperative morphine use during 48 hours after the surgery and a tendency to develop neuropathic pain (p=0.022).
CONCLUSIONS: Chronic neuropathic pain was uncommon in AIS patients who had undergone PSF surgery. Higher opioid consumption will increase the possibility of developing chronic neuropathic pain.
METHODS: Ninety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group.
RESULTS: There were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively.
CONCLUSION: Intraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia.
OBJECTIVE: The objective of this study is to determine the efficacy of high-dose versus low-dose tranexamic acid (TXA) in adolescent idiopathic scoliosis (AIS) corrective surgery.
SUMMARY OF BACKGROUND DATA: Corrective surgery for AIS is associated with significant blood loss. Evidence on the optimum TXA dose to reduce bleeding in pediatric population is scarce.
METHODS: A total of 166 AIS patients aged between 10 and 21 years, of American Society of Anesthesiologists (ASA) physical status I and II, preoperative hemoglobin >10 g/dL, platelet count >150,000 cells/L and Cobb angle of >45° scheduled for elective single-stage posterior spinal fusion (PSF) surgery by two attending surgeons were included between March 2017 and November 2018. Patients were randomized into Group A (High Dose, 30 mg/kg TXA loading dose followed by 10 mg/kg/h infusion) and Group B (Low Dose, 10 mg/kg TXA loading dose followed by 1 mg/kg/h infusion). The primary outcome was total surgical blood loss between both groups. Secondary outcomes were transfusion requirement, perioperative changes in hemoglobin and coagulation profiles, adverse events, and factors that influence total blood loss.
RESULTS: The mean total surgical blood loss between the two groups was not significant (Group A: 928.8 ± 406.1 mL [range: 348-1857 mL]; Group B: 918.1 ± 406.2 mL [range: 271-2000 mL], P = 0.865). The median duration of surgery was 120 minutes. One patient in each group received allogenic blood transfusion during the perioperative period. There were no significant changes in hemoglobin and coagulation profile at pre-operation, post-operation 0 hour and 48 hours. Sex, number of vertebral levels fused, and duration of surgery were independently associated with total surgical blood loss. No adverse events were observed perioperatively.
CONCLUSION: Low-dose TXA was as efficacious as high-dose TXA in reducing blood loss and allogenic blood transfusion for AIS patients undergoing PSF surgery.Level of Evidence: 1.
AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).
METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).
RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).
CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.
Materials and methods: We reviewed four patients with neurofibromatosis with severe PT spinal deformity. Case 1, a 16-year-old male presented with severe PT kyphoscoliosis (scoliosis: 89°, kyphosis: 124°) and thoracic myelopathy. Case 2 was a 14-year-old, skeletally immature male who presented with a PT lordoscoliosis (scoliosis: 85°). Case 3, a 13-year-old male, presented with severe PT kyphoscoliosis (scoliosis: 100°, kyphosis: 95°). Case 4, a 35-year-old gentleman, presented with severe PT kyphoscoliosis (scoliosis: 113°, kyphosis: 103°) and thoracic myelopathy. All patients underwent pre-operative halo-pelvic traction. After a period of traction, all patients underwent posterior spinal fusion (PSF) with autologous bone grafts (local and fibula bone grafts) and recombinant human bone morphogenetic protein-2 (rhBMP-2).
Results: Both patients with thoracic myelopathy regained near normal neurological status after halo-pelvic traction. Following traction, the scoliosis correction rate (CR) ranged from 18.0% to 38.9%, while the kyphosis CR ranged from 14.6% to 37.1%. Following PSF, the scoliosis CR ranged from 24.0% to 58.8%, while the kyphosis CR ranged from 29.1% to 47.4%. The total distraction ranged from 50-70mm. Duration of distraction ranged from 26-95 days. The most common complication encountered during halo-pelvic traction was pin-related e.g. pin tract infection, pin loosening and migration, osteomyelitis, and halo-pelvic strut breakage. No patients had cranial nerve palsies or neurological worsening.
Conclusion: Pre-operative correction of severe PT spinal deformities could be performed safely and effectively with the halo-pelvic device prior to definitive surgery.
SUMMARY OF BACKGROUND DATA: Prolonged operation duration in adolescent idiopathic scoliosis (AIS) surgery was associated with increased perioperative complications. However, the factors affecting operation duration in AIS surgery were unknown.
OBJECTIVE: The aim of the study was to investigate the factors affecting operation duration in posterior spinal fusion (PSF) surgery using a dual attending surgeon strategy among Lenke 1 and 2 AIS patients.
METHODS: In all, 260 AIS patients with Lenke 1 and 2 curves who underwent PSF were retrospectively reviewed. Preoperative and intraoperative factors affecting operation duration such as age, sex, height, weight, body mass index, Risser grade, Lenke subtypes, number of fusion level, number of screws, screw density, wound length, upper and lowest instrumented vertebrae level, preoperative Cobb angle, and flexibility of the major curve were assessed using univariate and multivariate linear regression analyses. Independent factors were determined when P-value <0.05.
RESULTS: The mean operation duration was 122.2±28.6 minutes. Significant independent factors affecting operation duration in PSF among Lenke 1 and 2 AIS patients were Lenke 2 subtypes (β=8.86, P=0.008), number of screws (β=7.01, P<0.001), wound length (β=1.14, P=0.009), and flexibility of the major curve (β=-0.25, P=0.005). The overall model fit was R2=0.525. Operation duration can be predicted using the formula: (8.86×Lenke subtypes)+(7.01×number of screws)+(1.14×wound length)-(0.25×flexibility)-0.54, where Lenke 2=1 and Lenke 1=0.
CONCLUSION: The factors affecting operation duration in PSF among Lenke 1 and 2 AIS patients were Lenke 2 curves, number of screws, wound length, and curve flexibility. The knowledge of these factors enables the spinal deformity surgeons to plan and estimate the operation duration before AIS surgery.
METHODS: Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded.
RESULTS: Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p = 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p = 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p = 0.28; evidence: very low).
CONCLUSION: Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.
DESIGN: Systematic review and meta-analysis of non-randomized trials.
PATIENTS: Databases of EMBASE, MEDLINE and CENTRAL were systematically searched from its inception until March 2021.
INTERVENTIONS: COVID-19 patients being positioned in the prone position either whilst awake or mechanically ventilated.
MEASUREMENTS: Primary outcomes were oxygenation parameters (PaO₂/FiO₂ ratio, PaCO₂, SpO₂). Secondary outcomes included the rate of intubation and mortality rate.
RESULTS: Thirty-five studies (n = 1712 patients) were included in this review. In comparison to the supine group, prone position significantly improved the PaO₂/FiO₂ ratio (study = 13, patients = 1002, Mean difference, MD 52.15, 95% CI 37.08 to 67.22; p
OBJECTIVES: We aimed to investigate the incidence of respiratory viruses in adult patients with suspected COVID-19 in Kuala Lumpur, Malaysia.
STUDY DESIGN: We collected 198 respiratory samples from adult patients hospitalized with suspected COVID-19 in a single teaching hospital in Kuala Lumpur in February-May 2020 and tested combined oro-nasopharyngeal swabs with the NxTAG Respiratory Pathogen Panel (Luminex) and Allplex RV Essential (Seegene) assays. Forty-five negative samples further underwent viral metagenomics analysis.
RESULTS: Of the 198 samples, 74 (37.4%) had respiratory pathogens, including 56 (28.3%) with SARS-CoV-2 and 18 (9.1%) positive for other respiratory pathogens. There were five (2.5%) SARS-CoV-2 co-infections, all with rhinovirus/enterovirus. Three samples (6.7%; 3/45) had viruses identified by metagenomics, including one case of enterovirus D68 and one of Saffold virus genotype 6 in a patient requiring ICU care. Most of the COVID-19 patients (91.1%; 51/56) had mild symptoms but 5.4% (3/56) died.
CONCLUSION: During the early COVID-19 period, common respiratory viruses other than SARS-CoV-2 only accounted for 9.1% of hospitalization cases with ARI and co-infections with SARS-CoV-2 were rare. Continued surveillance is important to understand the impact of COVID-19 and its associated public health control measures on circulation of other respiratory viruses. Metagenomics can identify unexpected or rare pathogens, such as Saffold virus, which is rarely described in adults.
OBJECTIVE: To analyze the amount of blood loss at different stages of Posterior Instrumented Spinal Fusion (PSF) surgery in adolescent idiopathic scoliosis (AIS) patients.
SUMMARY OF BACKGROUND DATA: Knowing the pattern of blood loss at different surgical stages may enable the surgical team to formulate a management strategy to reduce intraoperative blood loss.
METHODS: One hundred AIS patients who underwent PSF from January 2013 to December 2014 were recruited. The operation was divided into six stages; stage 1-exposure, stage 2-screw insertion, stage 3-release, stage 4-correction, stage 5-corticotomies and bone grafting, and stage 6-closure. The duration and blood loss at each stage was documented. The following values were calculated: total blood loss, blood loss per estimated blood volume, blood loss per minute, blood loss per vertebral level fused, and blood loss per minute per vertebral level fused.
RESULTS: There were 89 females and 11 males. The mean age was 17.0 ± 5.8 years old. Majority (50.0%) were Lenke 1 curve type. The mean preoperative major Cobb angle was 64.9 ± 15.0°. The mean number of levels fused was 9.5 ± 2.3 levels. The mean operating time was 188.5 ± 53.4 minutes with a mean total blood loss 951.0 ± 454.0 mLs. The highest mean blood loss occurred at stage 2 (301.0 ± 196.7 mL), followed by stage 4 (226.8 ± 171.2 mL) and stage 5 (161.5 ± 146.6 mL). The highest mean blood loss per minute was at stage 5 (17.1 ± 18.3 mL/min), followed by stage 3 (12.0 ± 10.8 mL/min). The highest mean blood loss per vertebral levels fused was at stage 2 (31.0 ± 17.7 mL/level), followed by stage 4 (23.9 ± 18.1 mL/level) and stage 5 (16.6 ± 13.3 mL/level).
CONCLUSION: All stages were significant contributors to the total blood loss except exposure (stage 1) and closure (stage 6). Blood loss per minute and blood loss per minute per level was highest during corticotomies (stage 5), followed by release (stage 3). However, the largest amount of total blood loss occurred during screw insertion (stage 2).
LEVEL OF EVIDENCE: 2.
METHODS:: This was a retrospective propensity score-matched study using prospectively collected data. Surgeries performed between 08:00 and 16:59 h were labeled as daytime surgeries (group 1) and surgeries performed between 17:00 and 06:00 h were labeled as after-hours surgeries (group 2). The perioperative outcome parameters were average operation time in and out, operation duration, intraoperative blood loss, blood transfusion, intraoperative hemodynamic parameters, preoperative hemoglobin, postoperative hemoglobin, and total patient-controlled anesthesia (PCA) morphine usage. Radiological variables assessed were Lenke subtypes, preoperative Cobb angle, number of fusion levels, number of screws used, postoperative Cobb angle, correction rate, side bending flexibility, side bending correction index, complications rate, and length of hospitalization.
RESULTS:: Average operation time in for daytime group was 11:32 ± 2:33 h versus 18:20 ± 1:05 h in after-hours group. Comparing daytime surgeries with after-hours surgeries, there were no significant differences ( p > 0.05) in the operation duration, intraoperative blood loss, intraoperative pH, bicarbonate, lactate, postoperative hemoglobin, hemoglobin drift, blood transfusion, postoperative Cobb angle, correction rate, side bending flexibility, side bending correction index, length of hospitalization, and complications rate. Total PCA morphine usage was significantly lesser in the after-hours group (18.2 ± 15.3 mg) compared with the daytime group (24.6 ± 16.6 mg; p = 0.042).
CONCLUSIONS:: After-hours elective spine deformity corrective surgeries for healthy ambulatory patients with AIS were as safe as when they were done during daytime.
OBJECTIVE: To investigate whether menses affect intraoperative blood loss in female adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF) surgeries.
SUMMARY OF BACKGROUND DATA: There were concerns whether patients having menses will have higher intraoperative blood loss if surgery were to be done during this period.
METHODS: This study included 372 females who were operated between May 2016 to May 2019. Fifty-five patients had menses during surgery (Group 1, G1) and 317 patients did not have menses during surgery (Group 2, G2). Propensity score matching (PSM) analysis with one-to-one, nearest neighbor matching technique and with a match tolerance of 0.001 was used. The main outcome measures were intraoperative blood loss (IBL), volume of blood salvaged, transfusion rate, preoperative hemoglobin, preoperative platelet, preoperative prothrombin time, preoperative activated partial thromboplastin time (APTT), international normalized ratio (INR), and postoperative hemoglobin. Postoperative Cobb angle and correction rate were also documented.
RESULTS: At the end of PSM analysis, 46 patients from each group were matched and balanced. The average operation duration for G1 was 140.8 ± 43.0 minutes compared with 143.1 ± 48.3 minutes in G2 (P = 0.806). The intraoperative blood loss for G1 was 904.3 ± 496.3 mL and for G2 was 907.9 ± 482.8 mL (P = 0.972). There was no significant difference in terms of normalized blood loss (NBL), volume of blood salvaged during surgery, preoperative hemoglobin, postoperative hemoglobin, hemoglobin drift, estimated blood volume (EBV), IBL per EBV and IBL per level fused (P > 0.05). No postoperative complications were encountered in both groups. On average, the postoperative hospital stay was 3.5 ± 0.8 days for both groups (P = 0.143).
CONCLUSION: Performing corrective surgery during the menstrual phase in female AIS patients is safe without risk of increased blood loss.
LEVEL OF EVIDENCE: 4.
METHODS: We prospectively recruited patients with Adolescent Idiopathic Scoliosis (AIS) scheduled for PSF surgery. The anatomical locations of pain were divided into four: (1) surgical wound pain; (2) shoulder pain; (3) neck pain; and (4) low back pain. The anatomical locations of pain were charted using the visual analogue pain score at intervals of 12, 24, 36, 48 hours; and from day-3 to -14. Patient-controlled analgesia (morphine), use of celecoxib capsules, acetaminophen tablets and oxycodone hydrochloride capsule consumption were recorded.
RESULTS: A total of 40 patients were recruited. Patients complained of surgical wound pain score of 6.2±2.1 after surgery. This subsequently reduced to 4.2±2.0 by day-4, and to 2.4±1.3 by day-7. Shoulder pain scores of symptomatic patients peaked to 4.2±2.7 at 24 hours and 36 hours which then reduced to 1.8±1.1 by day-8. Neck pain scores of symptomatic patients reduced from 4.2±1.9 at 12 hours to 1.8±1.1 by day-4. Low back pain scores of symptomatic patients reduced from 5.3±2.3 at 12 hours to 1.8±1.1 by day- 12.
CONCLUSIONS: Despite the presence of different anatomical locations of pain after surgery, surgical wound was the most significant pain and other anatomical locations of pain were generally mild. Surgical wound pain reduced to a tolerable level by day-4 when patients can then be comfortably discharged. This finding provides useful information for clinicians, patients and their caregivers.
STUDY DESIGN: Randomised controlled trial.
SETTING: Tertiary level hospital in Malaysia.
PATIENTS: 77 patients undergoing elective Caesarean delivery.
INTERVENTION: Differing speeds of spinal injection.
MEASUREMENTS: Systolic blood pressure was assessed every minute for the first 10min and incidence of hypotension (reduction in blood pressure of >30% of baseline) was recorded. The use of vasopressor and occurrence of nausea/vomiting were also recorded.
MAIN RESULTS: 36 patients in SLOW group and 41 patients in FAST group were recruited into the study. There was no significant difference in blood pressure drop of >30% (p=0.497) between the two groups. There was no difference in the amount of vasopressor used and incidence of nausea/vomiting in both groups.
CONCLUSION: In our study population, there was no difference in incidence of hypotension and nausea/vomiting when spinal injection time is prolonged beyond 15s to 60s.
TRIAL REGISTRATION: ClinicalTrials.govNCT02275897. Registered on 15 October 2014.
METHODS: A prospective randomized study was conducted in a single-center adult intensive care unit. In total, 100 patients were randomized into two groups. These patients underwent internal jugular vein central venous catheter cannulation with ultrasound guidance (short-axis scan, out-of-plane needling approach) in which one group adopted conventional method, while the other group was aided with the guided positioning system. Outcomes were measured by procedural efficacy (success rate, number of attempts, time to successful cannulation), complications, level of operators' experience, and their satisfaction.
RESULTS: All patients had successful cannulation on the first attempt except for one case in the conventional group. The median performance time for the guided positioning system method was longer (25.5 vs 15.5 s; p = 0.01). And 86% of the operators had more than 3-year experience in anesthesia. One post-insertion hematoma occurred in the conventional group. Only 88% of the operators using the guided positioning system method were satisfied compared to 100% in the conventional group.
CONCLUSION: Ultrasound-guided central venous catheter insertion via internal jugular vein was a safe procedure in both conventional and guided positioning system methods. The guided positioning system did not confer additional benefit but was associated with slower performance time and lower satisfaction level among the experienced operators.
METHODS: Retrospective study whereby 90 AIS patients (Lenke type 2, 3, 4, and 6) who underwent PSF from 2019 to 2023 were recruited. Twenty-five severe AIS patients were categorized in Gp1 and 65 non-severe AIS patients in Gp2. Propensity score matching (PSM) with one-to-one with nearest neighbor matching (match tolerance 0.05) was performed. Outcomes measured via operation duration of each stage of surgery, blood loss, number of screws, fusion levels and screw density.
RESULTS: Twenty-five patients from each group were matched. Total operative time was significantly higher in Gp1 (168.2 ± 30.8 vs. 133.3 ± 24.0 min, p