Transversus Abdominis Plane Block VS. Local Wound Infiltration for Elective Minimally Invasive Cholecystectomy in Children: A Prospective Randomized Trial.

BACKGROUND: The efficacy of transversus abdominis plane (TAP) block versus local anesthetic wound infiltration (LWI) in pediatric laparoscopic surgery is largely unknown. The objective of this study was to prospectively analyze this in minimally invasive cholecystectomy. We hypothesized that TAP block would be superior to LWI in terms of pain control and post-operative complications. METHODS: We conducted a prospective, randomized, single-blinded, controlled trial between 2017 and 2022 after obtaining Institutional Review Board (IRB) approval. After randomization, patients received a standard amount of ropivacaine via either 1) ultrasound-guided TAP block after general anesthesia induction or 2) local injection at port insertion by the operating surgeon. We collected data including operative time, pain scores, and medication usage post-operatively. We used descriptive statistics to report all endpoints and compared data with t-tests and Fisher's exact tests. A p-value less than 0.05 was considered statistically significant. RESULTS: We enrolled 85 patients (43 LWI, 42 TAP). Mean [standard deviation] age and body mass index (BMI) in the LWI and TAP groups were 14.8 [1.9] and 14.7 [2] years and 29.9 [7.2] and 27.4 [8.2] kilogram/meter2 (kg/m2) respectively. We did not find any significant differences in postoperative opioid use, pain scores, and gastrointestinal symptoms. TAP patients had significantly longer time between anesthesia-start and procedure-start (p < 0.001), although total time under anesthesia was not significantly different (p = 0.540). CONCLUSION: There are no significant differences between equal administration of local anesthetic by TAP block and surgeon administered LWI during minimally invasive cholecystectomy. TYPE OF STUDY: Randomized clinical trial. LEVEL OF EVIDENCE: Level II.

Preoperative optimization of cardiac valve patients' expectations: Study protocol of the randomized controlled ValvEx-trial.

Introduction: Complete recovery after surgery depends on psychological factors such as preoperative information, expectations, and surgery-associated anxiety. Prior studies have shown that even a short preoperative psychological intervention aiming at optimized expectations (EXPECT) can improve postoperative outcomes in coronary artery bypass patients. However, this intervention may benefit only a small subgroup of heart surgery patients since implementing preoperative psychological interventions into the daily clinical routine is difficult due to the additional time and appointments. It is unclear whether the EXPECT intervention can be shortened and whether heart valve patients would also benefit from interventions that optimize patients' expectations. The multicenter ValvEx trial aims (i) to adapt an effective preoperative psychological intervention (EXPECT) to make it brief enough to be easily integrated into the preoperative routine of heart valve patients and (ii) to examine if the adapted preoperative psychological intervention improves the subjectively perceived illness-related disability (PDI) up to 3 months after surgery. Materials and analysis: In two German university hospitals, N = 88 heart valve patients who undergo heart surgery are randomized into two groups [standard of care (SOC) vs. standard of care plus interventional expectation manipulation (SOC and EXPECT)] after baseline assessment. Patients in the EXPECT group additionally to standard of care participate in the preoperative psychological intervention (30-40 min), focusing on optimizing expectations and have two booster-telephone calls (4 and 8 weeks after the surgery, approx. 15 min). Both groups have assessments again on the evening before the surgery, 4 to 6 days, and 3 months after the surgery. Discussion: The trial demonstrates excellent feasibility in the clinical routine and a high interest by the patients. Ethics and dissemination: The Ethics Committees of the Department of Medicine of the Philipps University of Marburg and the Department of Medicine of the University of Giessen approved the study protocol. Study results will be published in peer-reviewed journals and presented at congresses. Clinical trial registration: ClinicalTrials.gov, identifier NCT04502121.

Pre-surgery optimization of patients' expectations to improve outcome in heart surgery: Study protocol of the randomized controlled multi-center PSY-HEART-II trial.

The PSY-HEART-I trial indicated that a brief expectation-focused intervention prior to heart surgery improves disability and quality of life 6 months after coronary artery bypass graft surgery (CABG). However, to investigate the clinical utility of such an intervention, a large multi-center trial is needed to generalize the results and their implications for the health care system. The PSY-HEART-II study aims to examine whether a preoperative psychological intervention targeting patients' expectations (EXPECT) can improve outcomes 6 months after CABG (with or without heart valve replacement). EXPECT will be compared to Standard of Care (SOC) and an intervention providing emotional support without targeting expectations (SUPPORT). In a 3-arm multi-center randomized, controlled, prospective trial (RCT), N = 567 patients scheduled for CABG surgery will be randomized to either SOC alone or SOC and EXPECT or SOC and SUPPORT. Patients will be randomized with a fixed unbalanced ratio of 3:3:1 (EXPECT: SUPPORT: SOC) to compare EXPECT to SOC and EXPECT to SUPPORT. Both psychological interventions consist of 2 in-person sessions (à 50 minute), 2 phone consultations (à 20 minute) during the week prior to surgery, and 1 booster phone consultation post-surgery 6 weeks later. Assessment will occur at baseline approx. 3-10 days before surgery, preoperatively the day before surgery, 4-6 days later, and 6 months after surgery. The study's primary end point will be patients' illness-related disability 6 months after surgery. Secondary outcomes will be patients' expectations, subjective illness beliefs, quality of life, length of hospital stay and blood sample parameters (eg, inflammatory parameters such as IL-6, IL-8, CRP). This large multi-center trial has the potential to corroborate and generalize the promising results of the PSY-HEART-I trial for routine care of cardiac surgery patients, and to stimulate revisions of treatment guidelines in heart surgery.

Baseline depressive symptoms, personal control, and concern moderate the effects of preoperative psychological interventions: the randomized controlled PSY-HEART trial.

This study examined whether baseline (3-14 days pre-surgery) levels of (i) depressive or (ii) anxiety symptoms and (iii) illness beliefs moderate the effects of additional preoperative interventions before coronary artery bypass graft surgery on (i) depressive or (ii) anxiety symptoms and (iii) illness beliefs 1 day before surgery, 1 week and 6 months after surgery. In the PSY-HEART trial, 115 patients were assessed. They were randomized into one of three groups: 1. receiving standard medical care only (SMC), additional psychological interventions: 2. aiming to optimize patients' expectations (EXPECT), or 3. focusing on emotional support. Patients with a higher baseline level of depressive symptoms receiving a preoperative psychological intervention indicated lower depressive symptoms 6 months after surgery compared to SMC. EXPECT increased personal control and concern levels in patients with low baseline personal control/concern 1 day before surgery. Brief preoperative psychological interventions can improve psychological outcomes in heart surgery patients. Baseline status may moderate these effects. The study has been approved by the medical ethics committee of the Philipps University of Marburg and has been pre-registered at www.clinicaltrials.gov (NCT01407055) on August 1, 2011.

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 OBJECTIVE: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. DESIGN: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). SETTING: Operating room. PATIENTS: Two 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). INTERVENTION: Randomized 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). MEASUREMENTS: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively. MAIN RESULTS: Baseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean Cmax in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to Cmax 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. CONCLUSIONS: Plasma 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.

Effect of leg lift on stroke volume index in children 11-17 years old before and after induction of general anesthesia.

BACKGROUND: Fluid administration in ERAS is one component which anesthesiologists have control. Change in stroke volume index (SVI) is used to assess fluid responsiveness. This study sought the effect of perioperative fluid responsiveness in pediatric patients. The Cheetah NICOM™ (noninvasive CO monitor) was employed because of correlation with other CO monitors. AIMS: The Cheetah NICOM™ is an FDA-approved device in adults. Its indications in children are unknown. 24 enrolled patients (age 11-17) were ASA 1 or 2 without cardiopulmonary disease. The study examined changes in SVI, HR, SBP, and DBP between the semi-recumbent and legs lifted positions, both awake and after anesthesia. METHODS: Each patient had baseline vital signs measured and fluid responsiveness determined with the Cheetah NICOM™ monitor. Stroke volume index (SVI) was measured in both the semi-recumbent position and after passive leg lift. Measurements were repeated immediately after induction of general anesthesia. Twenty-one of 24 patients received inhalation induction with sevoflurane and three patients received intravenous propofol followed by sevoflurane. Airway management included intubation in 19 of 24 and a laryngeal mask airway (LMA) in five of 24 patients. RESULTS: There was a 25% increase in SVI after leg lift from 54.8 ml/m2 to 68.0 ml/m2 in awake patients (p < 0.001). Diastolic pressure decreased by 15.4% from 67.9 mm Hg to 58.2 mm Hg from semi-recumbent position and leg lift, respectively (p = .004). No significant change in heart rate or SBP was found. Following induction, patient SVI increased with leg lift by 25.6% from 42.6 ml/m2 to 53.5 ml/m2 after leg lift (p = .003). Heart rate decreased by 9.3% and SBP increased 2.8% with leg lift. CONCLUSIONS: 96% of normal 11-17-year-old children were fluid responsive while awake and 79% after induction of general anesthesia.

Pharmacogenomics of methadone: a narrative review of the literature.

Background: Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to manage chronic and acute surgical pain. The variability in response to methadone has been widely recognized. The purpose of this article is to review the literature on the pharmacogenetic factors underlying this variability. Materials & methods: This is a narrative overview of the literature on the genetic variants affecting pharmacodynamics and pharmacokinetics of methadone, retrieved from searches of databases such as PubMed and google scholar. Discussion: Clinical responses to methadone may be affected by genetic variants in the opioidergic, dopaminergic and neurotrophic pathways. Polymorphisms in genes related to disposition and elimination of methadone alter the pharmacokinetics, and possibly pharmacodynamics of methadone. Cytochrome P450 enzymes and P-glycoprotein variants contribute to the interindividual variability in methadone pharmacokinetics. Evidence for single gene variants affecting methadone response remains weak. Multiple genetic variants must be considered in conjunction to improve predictive ability. Conclusion: Evidence remains scarce at this time, to recommend pharmacogenetic testing before methadone administration. Well-powered clinical studies are needed with population pharmacokinetic-pharmacodynamic modeling and multigenetic signature-based predictions to enable tailored use of methadone in clinical practice.

The Stability and Change of Loneliness Across the Life Span: A Meta-Analysis of Longitudinal Studies.

Individuals experience loneliness when they perceive a deficiency in the quality or quantity of their social relationships. In the present meta-analysis, we compiled data from 75 longitudinal studies conducted in Asia, Australia, Europe, and North America (N = 83, 679) to examine the rank-order and mean-level development of loneliness across the life span. Data were analyzed using two- and three-level meta-analyses and generalized additive mixed models. The results indicate that the rank order of loneliness is as stable as the rank order of personality traits and follows an inverted U-shaped trajectory across the life span. Regarding mean-level development, loneliness was found to decrease throughout childhood and to remain essentially stable from adolescence to oldest old age. Thus, in contrast to other personality characteristics, changes in loneliness are not generally related to age. Implications for theory are discussed.

Personalized pediatric anesthesia and pain management: problem-based review.

Pharmacogenetics, the genetic influence on the interpersonal variability in drug response, has enabled tailored pharmacotherapy and emerging 'personalized medicine.' Although oncology spearheaded the clinical implementation of personalized medicine, other specialties are rapidly catching up. In anesthesia, classical examples of genetically mediated idiosyncratic reactions have been long known (e.g., malignant hyperthermia and prolonged apnea after succinylcholine). The last two decades have witnessed an expanding body of pharmacogenetic evidence in anesthesia. This review highlights some of the prominent pharmacogenetic associations studied in anesthesia and pain management, with special focus on pediatric anesthesia.

Epidural Analgesia Decreases Narcotic Requirements in Patients with Low Level Spina Bifida Undergoing Urological Laparotomy for Neurogenic Bladder and Bowel.

PURPOSE: Concerns regarding anatomical anomalies and worsening neurological symptoms have prevented widespread use of epidural catheters in patients with low level spina bifida. We hypothesize that thoracic epidural placement in the T9 to T10 interspace is safe and decreases narcotic requirements following major open lower urinary tract reconstruction in patients with low level spina bifida. MATERIALS AND METHODS: We reviewed consecutive patients with low level spina bifida who underwent lower urinary tract reconstruction and received epidurals for postoperative pain control. Controls were patients with low level spina bifida who received single injection transversus abdominis plane blocks and underwent similar procedures. Complications of epidural placement, including changes in motor and sensory status, were recorded. Opioid consumption was calculated using equivalent intravenous morphine doses. Mean and maximum pain scores on postoperative days 0 to 3 were calculated. RESULTS: Ten patients with low level spina bifida who underwent lower urinary tract reconstruction with epidural were matched to 10 controls with low level spina bifida who underwent lower urinary tract reconstruction with transverse abdominis plane block. Groups were demographically similar. All patients had full abdominal sensation and functional levels at or below L3. No epidural complications or changes in neurological status were noted. The epidural group had decreased opioid consumption on postoperative days 0 to 3 (0.75 mg/kg vs 1.29 mg/kg, p = 0.04). Pain scores were similar or improved in the epidural group. CONCLUSIONS: Thoracic epidural analgesia appears to be a safe and effective opioid sparing option to assist with postoperative pain management following lower urinary tract reconstruction in individuals with low level spina bifida.

Genetics of perioperative pain management.

PURPOSE OF REVIEW: The current review will discuss the current literature on genetics of pain and analgesia, with special emphasis on perioperative setting. We will also discuss pharmacogenetics-based management guidelines, current clinical status and future perspectives. RECENT FINDINGS: Recent literature suggests that the interindividual variability in pain and postoperative analgesic response is at least in part because of one's genetic make-up. Some of the well characterized polymorphisms that are associated with surgical pain and opioid-related postoperative adverse outcomes are described in catechol-O-methyl transferase, CYP2D6 and µ-opioid receptor (OPRM1), ATP-binding cassette subfamily B member 1, ABCC3, organic cation transporter 1 genes. Clinical Pharmacogenetics Implementation Consortium has put forth recommendations on CYP2D6 genotype-based opioid selection and dosing. The list of drug-gene pairs studied continue to expand. SUMMARY: Pharmacogenetic approach marks the dawn of personalized pain medicine both in perioperative and chronic pain settings.

Antimicrobial susceptibility and molecular epidemiology of Neisseria gonorrhoeae in Germany.

Antimicrobial drug resistance in Neisseria gonorrhoeae has become an increasing public health problem. Hence, surveillance of resistance development is of crucial importance to implement adequate treatment guidelines. Data on the spread of antibiotic resistance among gonococcal isolates in Germany, however, is scarce. In a resistance surveillance study conducted by the Paul Ehrlich Society for Chemotherapy between October 2010 and December 2011, 23 laboratories all over Germany were requested to send N. gonorrhoeae isolates to the study laboratory in Frankfurt am Main. Species verification was performed biochemically using ApiNH and with Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing was performed using the Etest method. For molecular epidemiological analysis, N. gonorrhoeae strains were genotyped by means of N. gonorrhoeae multi-antigen sequence typing. A total of 213 consecutive gonococcal isolates were analyzed in this nationwide study. Applying EUCAST breakpoints, high resistance rates were found for ciprofloxacin (74%) and tetracycline (41%). Penicillin non-susceptibility was detected in 80% of isolates. The rate of azithromycin resistance was 6%, while all strains were susceptible to spectinomycin, cefixime, and ceftriaxone. Molecular typing of gonococcal isolates revealed a great heterogeneity of 99 different sequence types (ST), but ST1407 predominated (n=39). This is the first comprehensive German multi-centre surveillance study on antibiotic susceptibility and molecular epidemiology of N. gonorrhoeae with implications for antibiotic choice for treatment of gonorrhoea. The World Health Organization supports the concept that an efficacious treatment of gonorrhoea results in at least 95% of infections being cured. Accordingly, as spectinomycin is not available on the German market, only the third generation cephalosporins cefixime and ceftriaxone are regarded as valuable drugs for empirical treatment of gonorrhoea in Germany.

Endotracheal intubation versus laryngeal mask airway for esophagogastroduodenoscopy in children.

OBJECTIVES: The present study examined the safety and efficacy of a laryngeal mask airway (LMA), compared with an endotracheal tube (ETT), for children undergoing elective esophagogastroduodenoscopy (EGD). METHODS: A total of 84 American Society of Anesthesiologists (ASA) patients, status I to III, were randomly assigned to receive an ETT or LMA. All participants were premedicated with midazolam 0.5 mg/kg (up to 15 mg). Airway device placement occurred after induction with 8% sevoflurane and 100% oxygen, placement of an intravenous catheter, and intravenous lidocaine 2 mg/kg up to 100 mg. The following data were collected: time from induction of anesthesia to placement of the airway device, time from end of procedure to arrival in the postoperative acute care unit (PACU), time in the PACU, time from arrival in the operating room (OR) to discharge, vomiting after the procedure, nausea requiring medicine, lowest oxygen saturation, highest concentration of sevoflurane, highest pain, amount of pain medicine, adverse events, and satisfaction of doctor performing the EGD. RESULTS: Group ETT had higher time from room arrival to airway placement, mask to airway placement, room arrival time to discharge, mask placement to discharge, airway placement to discharge, and end of procedure to discharge. Group ETT had a higher proportion of patients with vomiting than group LMA. No statistical difference was noted in endoscopist satisfaction when comparing ETT and LMA. The ETT group had 3 adverse events, including laryngospasm (n=2) and asthma attack (n=1). CONCLUSIONS: The LMA appears to be an acceptable and safe alternative for otherwise healthy children undergoing routine EGD. Benefits appear to be decreased incidence of vomiting and overall decreased time spent in the hospital.

Gene associated with seizures, autism, and hepatomegaly in an Amish girl.

A genetic defect causing autism and epilepsy involving the contactin associated protein-like 2 gene (CNTNAP2) has been discovered in a selected cohort of Amish children. These children were found to have focal seizures and autistic regression. Surgical biopsy of the anterior temporal lobe of two such children revealed cortical dysplasia and a single nucleotide polymorphism mutation of this gene. The present case is that of a related but geographically distant proband with a similar phenotype but a single-base-pair deletion in the CNTNAP2 gene. This patient exhibited the additional features of periventricular leukomalacia and hepatomegaly.