The absence of dominant alpha-oscillatory EEG activity during emergence from delta-dominant anesthesia predicts neurocognitive impairment- results from a prospective observational trial

Study objectivePostoperative neurocognitive disorders (PND) are common complications after surgery under general anesthesia. In our aging society the incidence of PND will increase. Hence, interdisciplinary efforts should be taken to minimize the occurrence of PND. Electroencephalographic (EEG) monitoring of brain activity during anesthesia or emergence from anesthesia is a promising tool to identify patients at risk. We therefore investigated whether we could identify specific EEG signatures during emergence of anesthesia that are associated with the occurrence of PND.Design and patientsWe performed a prospective observational investigation on 116 patients to evaluate the EEG features during emergence from general anesthesia dominated by slow delta waves in patients with and without delirium in the postoperative care unit (PACU-D) as assessed by the CAM-ICU and the RASS.Main resultsDuring emergence both the frontal and global EEG of patients with PACU-D were significantly different from patients without PACU-D. PACU-D patients had lower relative alpha power and reduced fronto-parietal alpha coherence.ConclusionsWith our analysis we show differences in EEG features associated with anesthesia emergence in patients with and without PACU-D. Frontal and global EEG alpha-band features could help to identify patients with PACU-D.Clinical trial number: NCT03287401     

Perioperative supplemental oxygen and oxidative stress in patients undergoing moderate- to high-risk major abdominal surgery – A subanalysis of randomized clinical trial

Study objectiveOxidative stress plays a pivotal role in the development and aggravation of cardiovascular diseases. The influence of intraoperative inspired oxygen concentrations on oxidative stress is still not entirely known. Therefore, we evaluated in this sub-study if supplemental oxygen affects the oxidation-reduction potential in patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery.DesignSub-study of a prospective parallel-arm double-blinded single-center superiority randomized trial.SettingOperating room and postoperative recovery area.InterventionAdministration of 0.8 FiO₂ versus 0.3 FiO₂ throughout surgery and for the first two postoperative hours.MeasurementsThe primary outcome was the static oxidation-reduction potential (sORP) and the oxidation-reduction potential capacity (cORP) between both groups. The secondary outcome was the trend of sORP and cORP in the overall study population. We assessed sORP and cORP before induction of anesthesia, 2 h after induction of anesthesia, within 2 h after surgery and on the first and third postoperative day.Main results258 patients were analyzed. 128 patients were randomly assigned to the 80% oxygen group and 130 patients were randomly assigned to the 30% oxygen group. Postoperative sORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: −1.162 mV,95% CI: −2.584 to 0.260; p = 0.109). On average, we observed a change in sORP of 5.288 mV (95% CI:4.633 to 5.913, p < 0.001) per day. cORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: −0.015μC, (95%CI: −0.062 to 0.032; p = 0.524). On average, we observed a change in cORP values of −0.170μC (95%CI: −0.194 to −0.147, p < 0.001) per day.ConclusionIn contrast to previous reports, we could not find any evidence of an association between intraoperative supplemental oxygen and perioperative oxidative stress assessed by sORP and cORP.Trial registrationclinicaltrials.gov: NCT03366857 https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1     

Intraoperative hypotension is not associated with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia for surgery: results of a randomized controlled pilot trial

Study objectiveTo assess the effect of different intraoperative blood pressure targets on the development of POCD and test the feasibility of a larger trial.DesignRandomized controlled pilot trial.SettingPerioperative care in a tertiary care teaching hospital with outpatient follow-up.PatientsOne hundred one patients aged ≥75 years with ASA physical status <4, undergoing elective, non-cardiac surgery under general anesthesia and 33 age-matched healthy controls.InterventionsRandomization to a personalized intraoperative blood pressure target, mean arterial pressure (MAP) ≥ 90% of preoperative values (Target group), or to a more liberal intraoperative blood pressure management (No-Target group). Strategies to reach intraoperative blood pressure target were at discretion of anesthesiologists.MeasurementsAn experienced neuropsychologist performed a validated battery of neurocognitive tests preoperatively and 3 months after surgery. Incidence of POCD at three months and postoperative delirium were assessed. Intraoperative time spent with MAP ≥ 90% of preoperative values, recruitment and drop-out rate at 3 months were feasibility outcomes.Main resultsThe Target group spent a higher percentage of intraoperative time with MAP ≥90% of preoperative values (65 ± 25% vs. 49 ± 28%, p < 0.01). Incidence of POCD (11% vs. 7%, relative risk 1.52; 95% CI, 0.41 to 6.3; p = 0.56) and delirium (6% vs. 14%, relative risk, 0.44; 95% CI, 0.12 to 1.60; p = 0.21) did not differ between groups. No correlation was found between intraoperative hypotension and postoperative cognitive performance (p = 0.75) or delirium (p = 0.19). Recruitment rate was of 6 patients/month (95% confidential interval (CI), 5 to 7) and drop-out rate at 3 months was 24% (95% CI, 14 to 33%).ConclusionsIntraoperative hypotension did not correlate with postoperative cognitive dysfunction or delirium occurrence in elderly patients undergoing general anesthesia for non-cardiac surgery.A multicenter randomized controlled trial is needed in order to confirm the effect of intraoperative blood pressure on the development of POCD.Trial registration numberNCT02428062 www.clinicaltrials.gov.     

Outcomes of individualized goal-directed therapy based on cerebral oxygen balance in high-risk patients undergoing cardiac surgery: A randomized controlled trial

Study objectiveTo investigate whether optimizing individualized goal-directed therapy (GDT) based on cerebral oxygen balance in high-risk surgical patients would reduce postoperative morbidity.DesignThis was a prospective, randomized, controlled study.SettingThe study was performed in the First Affiliated Hospital of Anhui Medical University, Hefei, China, from April 2017 to July 2018.Patients146 high-risk adult patients undergoing valve replacements or coronary artery bypass surgery with cardiopulmonary bypass (CPB) were enrolled.InterventionPatients were randomized to an individualized GDT group or usual care group. Individualized GDT was targeted to achieve the following goals: A less than 20% decline in the regional cerebral oxygen saturation (rScO₂) level from baseline; a less than 20% decline in the mean arterial pressure (MAP) from baseline, as well as a bispectral index (BIS) of 45–60 before and after CPB and 40–45 during CPB.MeasurementsThe primary outcome was a composite endpoint of 30-day mortality and major postoperative complications.Main results128 completed the trial and were included in the modified intention-to-treat analysis. Early morbidity was similar between the GDT (25 [39%] of 65 patients) and usual care groups (33 [53%] of 63 patients) (relative risk 0.73, 95% CI 0.50–1.08; P = 0.15). Secondary analysis showed that 75 (59%) of 128 patients achieved individual targets (irrespective of intervention) and sustained less morbidity (relative risk 3.41, 95% CI 2.19–5.31; P < 0.001).ConclusionsIn high-risk patients undergoing cardiac surgery, individualized GDT therapy did not yield better outcomes, however, the achievement of preoperative individual targets may be associated with less morbidity.Trial registrationClinicaltrials.gov identifier: NCT03103633. Registered on 1 April 2017.     

Exploratory study of VVZ-149, a novel analgesic molecule,in the affective component of acute postoperative pain after laparoscopic colorectal surgery

Study objectiveVVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery.DesignRandomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526).Setting3 academic institutions in the United States.Patients60 patients undergoing laparoscopic colorectal surgery.InterventionsA continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia.MeasurementsThe outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided “as needed”. Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids.Main resultsPostoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group.ConclusionsVVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use.Registration numberwww.clinicaltrials.gov, ID: NCT02489526.     

The impact of social media presence,age, and patient reported wait times on physician review websites for sports medicine surgeons

BackgroundWhen choosing physicians, patients often review options online via physician review websites, which may influence decisions on providers.PurposeThe purpose of this study is to investigate the impacts of social media usage, age, and patient reported wait times on online ratings for three popular review websites.Study designCross-sectional study.MethodsThe American Orthopaedic Society for Sports Medicine database was used to extract demographic information for all listed sports medicine surgeons in Florida. Overall ratings, number of ratings and comments, and patient reported wait-times were recorded from three leading review websites (Healthgrades.com, Vitals.com, Google.com). Professionally focused SM accounts were searched for each physician on Facebook.com, Twitter.com, Instagram, and LinkedIn.com.Results102 orthopaedic sports medicine surgeons were included. At least one form of social media was used by 62.4% of our cohort. Those with social media had higher overall online physician ratings out of 5.00 across all review websites (Google:4.65vs4.44, p = 0.05; Healthgrades:4.41vs4.15, p = 0.03; Vitals:4.43vs4.14, p = 0.01). In bivariate analysis, older age was associated with lower ratings on Health Grades (Absolute difference (AD) −0.26, p < 0.0001), and social media was linked to higher ratings (Google: AD 0.21, p = 0.05; Healthgrades: AD 0.26, p = 0.03; Vitals: AD 0.29, p = 0.008). Longer wait times were associated with lower ratings in a dose-dependent manner in both bivariate and multivariable analysis.ConclusionsSocial media use among sports medicine surgeons correlated with higher overall physician ratings. Potentially, younger surgeons increase social media use because of a heightened concern for online image, whereas older surgeons may have less value in using online platforms to capitalize on an online presence. Older age and increased patient reported wait times in office had a negative correlation with online reviews, which highlights that factors beyond the surgeon's skill sets can influence overall ratings.     

Effects of remote ischemic preconditioning on regional cerebral oxygen saturation in patients in the beach chair position during shoulder surgery: A double-blind randomized controlled trial

Study objectiveThe beach chair position for shoulder surgery induces cerebral hypoperfusion. We evaluated the effects of remote ischemic preconditioning (RIPC) prior to surgery to ameliorate cerebral desaturation in a double-blind randomized fashion.DesignBlinded, prospective, randomized study.SettingOperating room & postoperative recovery room, tertiary university hospital.PatientsSeventy patients scheduled for shoulder surgery were recruited. After excluding 7 patients according to the exclusion criteria, 63 patients were randomized into two groups (control and RIPC).InterventionsRemote ischemic preconditioning was applied by briefly inflating a tourniquet on the thigh three times just after inducing anesthesia in the RIPC group.MeasurementsThe changes in regional cerebral oxygen saturation, hemodynamic values, laboratory values, and serum levels of cytokines including interleukin (IL)-1β, IL-6, IL-10 and transforming growth factor-β were measured.Main resultsThe remote ischemic preconditioning group had higher regional cerebral oxygen saturation just after establishment of the beach chair position (P = 0.002) and lower cerebral desaturation (P = 0.007) during operation than the control group. Hemodynamic and laboratory values did not differ between the groups. There were no significant intergroup differences in cytokine levels.ConclusionRemote ischemic preconditioning before surgery ameliorates cerebral desaturation in patients in the beach chair position during shoulder surgery.Trial Registry Number: KCT0001384 (http://cris.nih.go.kr)     

Transcutaneous electrical acupoint stimulation before surgery reduces chronic pain after mastectomy: A randomized clinical trial

Study objectiveDespite multiple interventions, the incidence of chronic pain after mastectomy could be as high as 50% after surgery. This study aimed to determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) before anesthesia induction in reducing chronic pain and to compare the effect of combined acupoint TEAS with that of single acupoint TEAS.DesignA multicenter randomized clinical trial.SettingThe study was conducted at six medical centers in China from May 2016 to April 2018. Final follow-up was on October 26, 2018.ParticipantsEligible patients were women scheduled for radical mastectomy under general anesthesia.InterventionsPatients were randomly and equally grouped into sham control (n = 188), single acupoint (PC6, n = 198), or combined acupoints (PC6 and CV17, n = 190) TEAS groups using a centralized computer-generated randomization system. TEAS was applied for 30 min before anesthesia induction. The sham-operated control group received electrode attachment but without stimulation. Anesthesiologists, surgeons, and outcome assessors were blinded to the interventions.MeasuresThe primary endpoint was the incidence of chronic pain 6 months after surgery. Incidences were compared among the groups using the unadjusted χ² test.ResultsOf the 576 randomized patients, 568 completed the trial. In the intention-to-treat analysis, post-mastectomy pain at 6 months was reported in 42 of 190 patients (22.1%) in the combined acupoints group, 65 of 188 patients (34.6%) in the sham-operated group (P = 0.007; relative risk [RR], 95% confidence interval [CI]: 0.68, 0.52–0.89), and 72 of 198 patients (36.4%) in the single acupoint group (P = 0.002; RR, 95% CI: 0.72, 0.55–0.93). Remifentanil consumption during surgery and postoperative nausea and vomiting at 24 h after surgery were lower in the combined acupoint group than that in the sham-operated group.ConclusionTEAS at combined acupoints before surgery was associated with reduced chronic pain 6 months after surgery.Trial registration: Clinicaltrials.gov identifier: NCT02741726. Registered on April 13, 2016.     

The effect of sevoflurane and isoflurane anesthesia on interictal spike activity among patients with refractory epilepsy.

The electrophysiologic effects of sevoflurane are not well characterized in humans. Among patients with refractory epilepsy, this study compared 1) electroencephalographic (EEG) interictal spike activity during wakefulness and sevoflurane anesthesia, and 2) electrocorticographically (ECoG) recorded interictal spike activity during sevoflurane and isoflurane anesthesia. We studied 12 patients undergoing insertion of subdural electrodes. Before commencing anesthesia, awake (baseline) EEG recordings were obtained. After inhaled induction, EEG interictal spike activity was evaluated during stable, normocapnic, and hypocapnic (Paco2 = 28-30 mm Hg), sevoflurane anesthesia administered at 1.5 times the minimum alveolar anesthetic concentration (1.5 MAC). Immediately after surgery, ECoG recordings were obtained from subdural electrodes during 1) 1.5 MAC isoflurane, 2) 0.3 MAC isoflurane, and 3) 1.5 MAC sevoflurane anesthesia. EEG spike frequency increased in all patients during sevoflurane anesthesia compared with awake recordings (P = 0.002). Compared with 0.3 MAC isoflurane anesthesia, ECoG interictal spike frequency was higher in all patients during 1.5 MAC sevoflurane anesthesia (P = 0.004) and in 8 of 10 patients during 1.5 MAC isoflurane anesthesia (P = 0.016). Under sufficiently rigorous conditions, both sevoflurane and isoflurane can provoke interictal spike activity at near burst-suppression doses. This property is more prominent with sevoflurane than isoflurane. IMPLICATIONS: The results of this study suggest that the capacity to modulate neuroexcitability is a dose-dependent feature of volatile anesthetics that is manifested most prominently at near burst-suppression doses (i.e., 1.5 times the minimum alveolar anesthetic concentration) and is minimal or absent at low doses.     

Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial

IntroductionThis report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND).MethodsThe ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1–2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQ-C30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.ResultsOverall, 976 questionnaires (501 in the SLN biopsy only group and 475 in the completion ALND group) were analysed, corresponding to a response rate of 82.6%. No significant group differences in overall HRQoL were identified. Participants receiving SLN biopsy only, reported significantly lower symptom scores on the EORTC subscales of pain, arm symptoms and breast symptoms. The Lymph-ICF domain scores of physical function, mental function and mobility activities were significantly in favour of the SLN biopsy only group.ConclusionOne year after surgery, arm morbidity is significantly worse affected by ALND than by SLN biopsy only. The results underline the importance of ongoing attempts to safely de-escalate axillary surgery.Trial registrationThe trial was registered at clinicaltrials.gov prior to initiation (https://clinicaltrials.gov/ct2/show/NCT 02240472).     

Nasal continuous positive pressure versus simple face mask oxygenation for adult obese and obstructive sleep apnea patients undergoing colonoscopy under propofol-based general anesthesia without tracheal intubation: A randomized controlled trial

Study objectiveTo determine if a nasal positive airway pressure (nasal CPAP) mask would decrease the number of hypoxemic events in obese and obstructive sleep apnea patients undergoing colonoscopy.DesignSingle-center prospective randomized controlled trial.SettingTertiary academic center.PatientsWe enrolled 109 patients with diagnosis of obesity and/or obstructive sleep apnea scheduled to undergo colonoscopy under propofol general anesthesia without planned tracheal intubation.InterventionPatients were randomly allocated (1:1 ratio) to receive supplementary oxygen at a flow of 10 L/min, either through a nasal CPAP or a simple facemask.MeasurementsThe primary endpoint was the difference in the mean percentage of time spent with oxygen saturation below 90% between the two groups. Secondary outcomes included the need for airway maneuvers/interventions, average SpO2 during the case, duration and severity of oxygen desaturation, incidence and duration of procedural interruptions, and satisfaction and tolerance scores.Main results54 were allocated to the simple face mask and 55 to the nasal CPAP mask arms, respectively. A total of 6 patients experienced a hypoxemic event. Among these patients, the difference in the percentage of time spent with oxygen saturation below 90% was not clinically relevant (p = 1.0). However, patients in the nasal CPAP group required less chin lift (20% vs. 42.6%; p = 0.01) and oral cannula insertion (12.7% vs.29.6%; p = 0.03). The percentage of patients with at least one airway maneuver was higher in the simple face mask arm (68.5% vs. 41.8%; p = 0.005). Patient tolerance to device score was lower in the nasal CPAP group (8.85 vs. 9.56; p = 0.003).ConclusionsA nasal CPAP did not prevent hypoxemia and should not be used routinely for colonoscopy in obese or OSA patients if a simple face mask is an alternative therapy. However, potential advantages of its use include fewer airway maneuvers or interventions, which may be desirable in certain clinical settings.Trial registrationClinicaltrials.gov, identifier: NCT05175573.     

Ultrasound-assisted spinal anesthesia: A randomized comparison between midline and paramedian approaches

Study objectiveNeuraxial ultrasonography can improve the technical performance of spinal anesthesia. However, there are no data regarding the optimal approach for ultrasound-assisted spinal anesthesia. This study aimed to compare the midline and paramedian approaches for ultrasound-assisted spinal anesthesia in adult orthopedic patients.DesignA single-center, prospective, randomized controlled trial.SettingOperating room.PatientsOne hundred and twelve patients undergoing orthopedic surgery were included.InterventionsPatients were randomized to undergo either the midline or paramedian approach for preprocedural ultrasound-assisted spinal anesthesia.MeasurementsThe primary outcome was the number of needle passes required for successful dural puncture. Secondary outcomes were the number of needle insertions, first pass/attempt success rate, procedural time, and the incidence of periprocedural complications.Main resultsThe median number of needle passes was significantly lower in the paramedian group (1 [IQR, 1–2]) than in the midline group (3 [2–6]; P < 0.001). The paramedian approach showed higher first pass/attempt success rates compared with the midline group (58.9% vs. 21.4%; 91.1% vs. 53.6%; both, P < 0.001). Total procedure times were significantly shorter in the paramedian group than in the midline group (113 [72.5–146.5] vs. 196 [138–298.5] seconds; P < 0.001). The quality of sonographic images was graded as good in 94.6% of paramedian sagittal oblique views and 54.5% of transverse median views. No significant intergroup differences were found in the incidence of periprocedural complications.ConclusionsCompared with the midline approach, the ultrasound-assisted paramedian approach showed improved efficacy in terms of the number of needle manipulations, first pass success rates, and procedural time. These results suggest that the paramedian approach may be more efficient for preprocedural ultrasound-assisted spinal anesthesia.Trial registration numberNCT03491943     

Erector spinae plane block and thoracic paravertebral block for breast surgery compared to IV-morphine: A randomized controlled trial

Study objectiveErector spinae plane (ESP) block is a novel regional anesthesia technique and gaining importance for postoperative pain management. Since it was first described, the clinicians wonder if this new simple technique can replace paravertebral block (PVB). We aimed to compare the postoperative analgesic effect of ESP block and PVB with a control group in breast surgeries.DesignRandomized controlled trial.SettingOperating room.PatientsSeventy-five ASA I–II patients aged 25–65, who were scheduled to go under elective unilateral breast surgery for breast cancer were included to the study.InterventionsPatients were randomized into three groups as ESP, PVB, and Control group. Ultrasound (US) guided ESP block and PVB with 20 ml 0.25% bupivacaine was done preoperatively to the patients according to their groups.MeasurementsAll patients were provided with iv patient-controlled analgesia device for postoperative analgesia. Morphine consumptions and numeric rating scale (NRS) scores for pain were recorded at 1st, 6th, 12th and 24th hours postoperatively.Main resultsThere was a statistically significant difference between ESP and Control groups (p < 0,001) and between PVB and Control groups (p < 0,001), while there was no difference between ESP and PVB groups (p > 0,05) for 24-hour morphine consumptions. There was a significant difference between PVB and Control groups for NRS at postoperative 1st and 6th hour (p = 0.018 and p = 0.027 respectively).ConclusionsThis study has shown that US guided ESP block and PVB provided adequate analgesia in patients undergoing breast surgery and have an opioid sparing effect by reducing morphine consumption.Clinical Trials Registry: NCT03480958.     

Anticholinergic burden of long-term medication is an independent risk factor for the development of postoperative delirium: A clinical trial

BackgroundPostoperative delirium (POD) is a common complication after surgery.ObjectiveWe sought to determine the association between preoperative anticholinergic load calculated using the anticholinergic drug scale (ADS) and POD in cancer patients over 65 years of age.DesignA retrospective sub-investigation of a randomised controlled interventional trial.SettingTwo tertiary university hospitals.PatientsOverall, patients aged 65 years and older scheduled for surgical treatment of gastrointestinary, genitourinary or gynaecological cancers.Main outcome measuresThe primary outcome was the interaction between anticholinergic drug scale and occurrence of postoperative delirium. Patient clinical parameters and ADS scores were assessed preoperatively. POD screening was conducted for a total of 7 days following surgery using validated measures. Independent associations between ADS and POD were assessed using multivariate logistical regression analyses.ResultsA total of 651 patients (mean age, 71.8 years; 68.5% males) were included. Of those, 66 patients (10.1%) developed POD. The ADS score was independently associated with the occurrence of POD (higher ADS per point OR 1.496; 95% CI 1.09–2.05; p = 0.01). Additionally, age (per year OR 1.06; CI 95% CI 1.01–1.11; p = 0.03) and ASA state (OR 2.16; 95% CI 1.22–3.83; p = 0.01), as well as stay on ICU (yes vs. no OR 2.8; 95% CI 1.57–4.998; p < 0.01), were independently associated with POD.ConclusionsADS assessment according to chronic medication use is a cost-effective, non-invasive method of identifying elderly cancer patients at risk for POD.Trial registry: www.clinicaltrials.gov. Identifier NCT01278537.Ethics: IRB of Charité University-Medicine Berlin, Germany; EA2/241/08.     

A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY)

Study objectiveTo evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.DesignMulticenter, open-label, phase 3, randomized trial (PLAY; NCT03682302).SettingOperating room.PatientsTwo separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery).InterventionRandomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2).MeasurementsThe primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [C_max], time to C_max) and safety of liposomal bupivacaine, respectively.Main resultsBaseline characteristics were comparable across groups. Mean C_max after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean C_max in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to C_max of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths.ConclusionsPlasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000–4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302     

Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial

Study objectiveDelirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment.The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100β were measured to investigate their dynamics in delirious and non-delirious patients after surgery.DesignThe Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial.SettingPerioperative care.Patients182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia.InterventionsPre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo.MeasurementsAssessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay.Main resultsNone of the three study arms – haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100β levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups.ConclusionsThe study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100β trajectories in patients with cognitive deterioration suggest affection of glial cells in particular.Trial registrationClinicalTrials.gov NCT02433041; registered on April 7, 2015.     

Preoperative Duloxetine to improve acute pain and quality of recovery in patients undergoing modified radical mastectomy: A dose-ranging randomized controlled trial

ObjectiveDuloxetine has been recently used as a part of multimodal analgesia in perioperative settings, yet the optimal dose of Duloxetine is not determined.DesignA parallel, randomized, placebo-controlled trial.SettingTertiary level oncology center.Patients88 female patients with breast cancer were subjected to modified radical mastectomy (MRM) with ASA class I and II were recruited.InterventionParticipants were randomly allocated into 4 equal groups received 2 h preoperatively, placebo (D0, N = 22), Duloxetine 30 mg (D30, N = 22), Duloxetine 60 mg (D60, N = 22) and Duloxetine 90 mg (D90, N = 22) tablet.MeasurementsThe primary outcome; 24 h cumulative postoperative morphine consumption and the secondary outcomes; VAS score of pain intensity, quality of recovery (QoR-40), time to Aldrete 9, and side effects (sedation and vomiting) were measured.ResultsThe median (IQR) consumption of morphine (mg) in the first postoperative 24 h was significantly decreased in both (D60 and D90) groups compared to (D0 and D30) groups, P < 0.001(Bonferroni corrected), however, a non-significant reduction was observed between D90 group vs. D60 group and D30 group vs. D0 group, P = 0.595 and P = 0.462 respectively, D60 vs. D0; 0(0–6) vs. 10(9–12), D60 vs. D30; 0(0–6) vs. 9(8–11), D90 vs. D0; 0(0–5) vs. 10(9–12), D90 vs. D30; 0(0–5) vs. 9(8–11), D90 vs. D60; 0(0–5) vs. 0(0–6), D30 vs. D0; 9(8–11) vs. 10(9–12), patients in D90 group took longer time to recover from anesthesia “ time to Aldrete 9” and showed an increased level of sedation in comparison with other groups, vomiting was more frequent in the D90 group.ConclusionPreoperative oral Duloxetine of 60 mg, for patients subjected to MRM is the optimal dose considering its analgesic efficacy and side effects.Trial registrationThe trial was registered at Clinical Trials.gov with unique ID number; NCT03468348.     

Association of pharmacological prophylaxis with the risk of pediatric emergence delirium after sevoflurane anesthesia: An updated network meta-analysis

Study objectiveThis updated network meta-analysis aims at exploring whether the concurrent use of midazolam or antiemetics may enhance the efficacy of other pharmacological regimens for delirium prophylaxis in pediatric population after general anesthesia (GA).DesignNetwork meta-analysis (PROSPERO registration: CRD42020179483).SettingPostoperative recovery area.PatientsPediatric patients undergoing GA with sevoflurane.InterventionsPharmacological interventions applied during GA with sevoflurane.MeasurementsThis network meta-analysis of randomized controlled trials (RCTs) was conducted with a frequentist model. PubMed, Embase, ProQuest, ScienceDirect, Cochrane CENTRAL, ClinicalKey, Web of Science, and ClinicalTrials.gov were searched from their inception dates to April 12, 2020, for RCTs of either placebo-controlled or active-controlled design containing information on the incidence of emergence delirium in pediatric patients undergoing sevoflurane anesthesia.Main resultsSeventy studies comprising 6904 participants were included for the analysis of 30 pharmacological interventions. Based on surface under the cumulative ranking curve (SUCRA) analysis, midazolam was ranked the lowest in therapeutic effect (SUCRA: 20%), while antiemetics as a monotherapy had no effect on delirium prophylaxis. However, there was a trend that most combination therapies with midazolam or antiemetics were superior to monotherapies for delirium prophylaxis. Subgroup analyses based on age (i.e., ≤7 years) and a validated scoring system (i.e., the Pediatric Anesthesia Emergence Delirium scale) for delirium also suggested a better efficacy of combination therapies than monotherapies. Overall, combination therapies with midazolam or antiemetics did not have a negative impact on the incidence of postoperative nausea and vomiting, length of stay in the postanesthesia care unit, or time to extubation. The dexmedetomidine-midazolam-antiemetic combination was the most effective strategy for the prevention of emergence delirium.ConclusionsThis network meta-analysis suggested that the incorporation of midazolam or antiemetics as adjuncts for combination therapies may have synergistic effects against pediatric postoperative emergence delirium. Future large-scale placebo-controlled RCTs are warranted to validate our findings.     

Preoperative oximetry-derived hypoxemia predicts postoperative cardiovascular events in surgical patients with unrecognized obstructive sleep apnea

Study objectiveObstructive sleep apnea (OSA) is known to be associated with postoperative cardiovascular events in patients undergoing major non-cardiac surgery. The objective of the study is to determine whether preoperative oximetry-derived hypoxemia predicts postoperative cardiovascular events in surgical patients with unrecognized obstructive sleep apnea.Design and settingThe study was a planned post hoc analyses of a multicenter prospective cohort study.PatientsThe inclusion criteria were patients ≥45 years old undergoing major non-cardiac surgery with cardiovascular risk factors.Interventions and measurementsAll patients underwent pre-operative pulse oximetry (PULSOX-300i, Konica-Minolta Sensing, Inc). The severity of OSA was classified based on oxygen desaturation index (ODI) (mild: ≥5 to <15, moderate: ≥15 to <30, and severe OSA: ≥30 events/h). The 30 days cardiovascular events were a composite of myocardial injury, cardiac death, congestive heart failure, thromboembolism, atrial fibrillation, and stroke.Main resultsFor 1218 patients with mild, moderate, or severe OSA (mean age: 67.2 ± 9.3 years; body mass index: 27.0 ± 5.3 kg/m²), the rate of postoperative cardiovascular events was 16.4%, 25.2%, and 29.8% respectively. The multivariable analysis showed that preoperative oxygen desaturation index (ODI) ≥30 events per hour {adjusted hazard ratio (aHR) 1.63 [95% confidence interval (CI): 1.05–2.53]}, and cumulative time spent during sleep with oxygen saturation below 80% (CT80) ≥10 min {aHR 1.79 [95% CI: 1.28–2.50]} were independent predictors of 30-day postoperative cardiovascular events.ConclusionsPreoperative ODI ≥30 events per hour and CT80 ≥ 10 min are associated with increased risk of postoperative cardiovascular events. Preoperative screening using oximetry helps in risk stratification for unrecognized sleep apnea.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01494181