Evaluating the Predictive Value of a Short Preoperative Holistic Risk Factor Screening Questionnaire in Preventing Persistent Pain in Elective Adult Surgery: Study Protocol for a Prospective Observational Pragmatic Trial [PERISCOPE].

Background: The global incidence of persistent pain after surgery is approximately 10%, with considerable clinical and socioeconomic impacts. Despite identifying many risk factors in its development and the challenging management of the often neuropathic pain complaints, preoperative recognition of high-risk patients in various surgical populations using a standardized risk factor assessment questionnaire is lacking. This study evaluates the predictive value of a short holistic risk factor screening questionnaire as a first step in preventing and treating persistent pain in adults undergoing elective surgery. Methods: This prospective observational pragmatic trial will include 560 adults undergoing elective surgery. The primary endpoint is the evaluation of the predictive value of the screening questionnaire, including the optimal cut-off determination in terms of sensitivity and specificity for inclusion in a perioperative high-vigilance program. Secondary endpoints are postoperative pain (intensity and characterization using the NRS and DN4), postoperative analgesic usage, and well-being using the EQ-5D-5 L. To assess the performance of the designed screening questionnaire in the identification of psychosocial pain aspects, HADs, and STAI-trait are being surveyed. Additionally, the multidimensional pain inventory (MPI, part 1) is being used to assess the impact of pain on daily life in patients. Discussion: This pragmatic clinical trial will evaluate a short preoperative screening questionnaire to predict persistent postoperative pain after elective surgery in adults. Suppose high-risk patients could be identified earlier using this short preoperative holistic screening questionnaire. In that case, it might contribute to a more widespread implementation of standardized preoperative assessment and awareness for preventing persistent postoperative pain. Trial Registration: Local ethics committee: B3002022000112. ClinicalTrials.gov identifier: NCT05526976. Registered on: 02 September 2022. Start of recruitment: 22 December 2022. Trial Status: This paper is based on protocol version 4.0. The first patient was assigned to the research project on the 22 of December 2022. We anticipate including the last patient in October 2023 and plan to finalize the study by January 2024.

Pupillary reflex dilation and pain index evaluation during general anesthesia using sufentanil: a double-blind randomized controlled trial.

Aim: In a single-center, double-blind, randomized controlled trial, we evaluated whether pupillometry-controlled use of sufentanil is better than free-choice administration of sufentanil by anesthesiologists. Patients & methods: 61 patients undergoing daycare gynecological or abdominal surgery were enrolled. A pupillometry pain index score chart was introduced for administration guidance of sufentanil. Results: The first objective, patient well-being, did not show a significant difference with painkiller usage and health state index at day 1 postoperatively. Second, we experienced difficulty in interpretation of the pupillometry score. Third, opioid usage was higher in the intervention group (20.1 vs 14.8 mcg; p = 0.017). Conclusion: The use of pupillometry and pain index chart for bolus sufentanil with our protocol showed an unwanted higher sufentanil usage without a significant difference in patient wellbeing. (Ethics Committee EC17/28/319 of the University Hospital of Antwerp. Registration at clinicaltrials.gov NCT03248908).

Communication with patients under general anesthesia is impossible. A potential solution is to measure pain. One of seven commercially available options is to use a pupillometer. Automated painful stimuli are given and the dilation of the pupil is measured. We hoped to use this method to better control the dose of the opioid sufentanil. During daycare gynecological and abdominal procedures, we had a 25% higher sufentanil usage in the intervention group. We experienced difficulties in reaching the right pain score in both groups. The well-being of the patients, namely pain and painkiller usage at day 1 after surgery, did not show any significant difference. With our protocol, there is no benefit to controlling the dose of sufentanil by pupillometer measurement.

Integrated Analgesic Care in the Current Human Monkeypox Outbreak: Perspectives on an Integrated and Holistic Approach Combining Old Allies with Innovative Technologies.

Monkeypox (MPX) is a zoonotic infection caused by an orthopoxvirus that is endemic to Central and Western Africa. The MPX virus is a part of the same family of viruses as the variola virus, which causes smallpox. Since May 2022, there has been a global increase in the incidence of MPX infections in multiple countries where the illness is not usually prevalent. A growing number of publications have emphasized on the need for increased awareness among all health professionals for the rapid recognition and diagnosis of this disease and for proper public health measures. However, atypical presentations and occurrence of uncommon symptoms receive less than the desired attention. More specifically, MPX infection related nociceptive symptoms are currently underexposed. Nevertheless, reports from the current outbreak have revealed that (severe) pain is one of the major causes for distress and even hospitalization in these patients. As for all serious pain conditions, an integrated, multidisciplinary, and holistic approach is indicated. This approach should be multimodal and include non-pharmacological therapies alongside pharmacological approaches. Health care professionals should be aware of available alternatives when first choice analgesic therapies fail. Protocols for identification of pain type and prolonged monitoring of clinical status should be implemented to improve patient well-being during acute infection, but also prevent chronic nociceptive syndromes.

Real-time Monitoring of Cerebral Blood Flow and Cerebral Oxygenation During Rapid Ventricular Pacing in Neurovascular Surgery: A Pilot Study.

BACKGROUND: Rapid ventricular pacing (RVP) can be used to produce short periods of flow arrest during dissection or rupture of a cerebral aneurysm but carries the risk of inducing cerebral ischemia. This study evaluates the intraoperative effect of RVP on local cerebral blood flow (CBF) and cerebral oxygenation during neurovascular surgery. MATERIALS AND METHODS: Five patients undergoing elective cerebrovascular surgery were included in a single-center prospective study. RVP was applied in pacing periods of 40 seconds with 30% and 100% FiO2. Regional cerebral oxygenation was monitored using a Foresight near-infrared spectroscopy sensor. A Clark-type electrode and a thermal diffusion microprobe located in the white matter were used to monitor brain tissue pO2 and CBF, respectively. RESULTS: CBF response to RVP closely followed the blood pressure pattern and resulted in a low-flow state. Unlike CBF, brain tissue pO2 and regional cerebral oxygenation showed a delayed response to RVP, decreasing beyond the pacing period and slowly recovering after RVP cessation. We found a correlation between brain tissue pO2 and regional cerebral oxygenation. Increasing the inspired oxygen concentration had a positive impact on absolute regional cerebral oxygenation and brain tissue pO2 values, but the pattern resulting from applying RVP remained unaltered. CONCLUSIONS: RVP reduces CBF and cerebral oxygenation. Brain tissue pO2 and regional cerebral oxygenation are correlated but unlike CBF respond to RVP in a delayed manner. Further research is required to evaluate the impact of longer RVP bursts on brain oxygenation.

Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial.

BACKGROUND: The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission. METHODS: This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath. RESULTS: For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3-9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group. CONCLUSIONS: In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013-001926-25 on October 10, 2013.

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex.

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and long-term consequences of unresolved pain or excessive analgosedation, adequate nociceptive monitoring remains challenging in non-communicative, critically ill adults. In the intensive care unit (ICU), routine nociceptive evaluation is carried out by the attending nurse using the Behavior Pain Scale (BPS) in mechanically ventilated patients. This assessment is limited by medication use (e.g., neuromuscular blocking agents) and the inherent subjective character of nociceptive evaluation by third parties. Here, we describe the use of two nociceptive reflex testing devices as tools for objective pain evaluation: the pupillary dilation reflex (PDR) and nociception flexion reflex (NFR). These measurement tools are non-invasive and well tolerated, providing clinicians and researchers with objective information regarding two different nociceptive processing pathways: (1) the pain-related autonomic reactivity and (2) the ascending component of the somatosensory system. The use of PDR and NFR measurements are currently limited to specialized pain clinics and research institutions because of impressions that these are technically demanding or time-consuming procedures, or even because of a lack of knowledge regarding their existence. By focusing on the two abovementioned nociceptive reflex assessments, this study evaluated their feasibility as a physiological pain measurement method in daily practice. Pursuing novel technologies for evaluating the analgesia level in unconscious patients may further improve individual pharmacological treatment and patient related outcome measures. Therefore, future research must include large well-designed clinical trials in a real-life environment.

Rapid Ventricular Pacing for Neurovascular Surgery: A Study on Cardiac and Cerebral Effects.

BACKGROUND AND OBJECTIVE: Intraoperative rupture of a cerebral aneurysm during neurosurgery can be a devastating event that increases perioperative morbidity and mortality. Rapid ventricular pacing (RVP) is a technique to obtain flow arrest for short periods of time during dissection or rupture of the aneurysm. The objective of this study was to evaluate the neurological and cardiac effects of repetitive periods of RVP during cerebrovascular surgery. METHODS: Data from patients who underwent repetitive RVP during craniotomy for cerebrovascular disorders were retrospectively analyzed from a single-center medical records database (Cegeka Medical Health Care Systems). We compared preoperative and postoperative troponin levels (cTnI) to assess cardiac ischemia. Preoperative and postoperative magnetic resonance imaging (MRI) results were screened for RVP-induced infarcts by evaluating diffusion restriction in the hemisphere contralateral to the operated side and the fossa posterior. RESULTS: A total of 37 patients were analyzed. An immediate decrease of systolic arterial blood pressure (<60 mm Hg) was achieved after initiation of RVP. Postoperative MRI did not reveal areas of diffusion restriction. RVP tended to be a predictor of postoperative cTnI increase. Preoperative and postoperative cTnI levels were higher in patients with a subarachnoid hemorrhage compared to patients without one. After 24 hours cTnI jevels normalized to preoperative values. CONCLUSIONS: Systolic arterial blood pressure decreased after RVP but normalized immediately when pacing stopped. MRI of the brain did not show RVP-related ischemia and the limited cTnI level increase normalized to preoperative values. Therefore, RVP during short periods of time seems to be a safe blood pressure-lowering technique for the brain and heart.

Preliminary Evaluation of a Web-Based Psychological Screening Tool in Adolescents Undergoing Minimally Invasive Pectus Surgery: Single-Center Observational Cohort Study.

BACKGROUND: Preoperative anxiety and depression are predominant risk factors for increased postoperative pain. Thoracic wall deformities in adolescents often cause low self-esteem, which contributes to psychological concerns. Several studies have suggested a relationship between preoperative mental health support and enhanced recovery after surgery. OBJECTIVE: This study investigated the validity of screening questionnaires concerning psychological trait and state characteristics via a patient-specific online platform. METHODS: Patients scheduled for elective pectus surgery between June 2017 and August 2017 were invited to participate in clinical interviews and online self-report questionnaires. All patients were recruited in the Anesthesiology Department, Antwerp University Hospital, Belgium. This single-center observational cohort study was performed in accordance with the ethical standards of the International Council for Harmonisation-Good Clinical Practice guidelines and the Declaration of Helsinki after obtaining study approval by the Institutional Review Board and Ethics Committee of the Antwerp University Hospital, Belgium (study identifier: 17/08/082). An online preoperative psychological inventory was performed using the Rosenberg Self-Esteem Scale, Hospital Anxiety and Depression Scale, and State-Trait Anxiety Inventory. Postoperatively, pain intensity and interference were assessed using the Multidisciplinary Pain Inventory, Coping With Pain Questionnaire, and numeric pain rating scale assessment. Patient satisfaction of the Web-based platform was evaluated. RESULTS: A total of 21 adolescent patients used our Web-based psychological perioperative screening platform. Patients rated the mobile phone app, usability, and accessibility of the digital platform as good or excellent in 85% (17/20), 89% (17/19), and 95% (20/21) of the cases, respectively. A total of 89% (17/19) of the patients rated the effort of generating answers to the online questionnaires as low. The results from the completed questionnaires indicated a strong negative correlation between self-esteem and the anxiety trait (R=-0.72, P<.001) and overall anxiety characteristics (R=-0.49, P=.04). There was a positive correlation between depressive and anxiety characteristics and the anxiety trait (R=0.52, P=.03 and R=0.6, P=.02, respectively) measured by the online self-report questionnaires. Moreover, preoperative anxiety was positively correlated with postoperative pain interference (R=0.58, P=.02). Finally, there was a negative correlation between self-esteem and pain interference (R=-0.62, P=.01). Conclusions: Perioperative screening of psychological symptoms and trait characteristics with specific treatment, if necessary, could further improve postoperative pain and overall health status. Research on eHealth technology, even for psychological patient care, is rapidly increasing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03100669; https://clinicaltrials.gov/ct2/show/NCT03100669 (Archived by WebCite at http://www.webcitation.org/6zPvHDhU5).

Pupillary dilation reflex and pupillary pain index evaluation during general anaesthesia: a pilot study.

BACKGROUND: Pupillary response by pupillary dilatation reflex (PDR) is a robust reflex, even measurable during general anaesthesia. However, the ability of infrared pupillometry to detect PDR differences obtained by intraoperative opioid administration in anaesthesized patients remains largely unknown. We analyzed the performance of automated infrared pupillometry in detecting differences in pupillary dilatation reflex response by a inbuilt standardized nociceptive stimulation program in patients under general anesthesia with a standardized propofol/fentanyl scheme. METHODS: In this single center, interventional cohort study 38 patients (24-74 years) were enrolled. Patients were anesthetized with propofol until loss of consciousness. Two dynamic pupil measurements were performed in each patient (before opioid administration and after opioid steady state). Automated infrared pupillometry was used to determine PDR during nociceptive stimulations (10-60 mA) applied by a inbuilt pupillary pain index protocol (PPI) to the skin area innervated by the median nerve. Increasing stimulations by protocol are device specific and automatically performed until pupil dilation of > 13%. Pupil characteristics, blood pressure, heart rate values were collected. RESULTS: After opioid administration, patients needed a higher stimulation intensity (45.26 mA vs 30.79 mA, p = 0.00001). PPI score showed a reduction after analgesic treatment (5.21 vs 7.68, p = 0.000001), resulting in a 32.16% score reduction. CONCLUSIONS: PDR via automated increased tetanic stimulation may reflect opioid effect under general anaesthesia. Further research is required to detect possible confounding factors such as medication interaction and optimization of individualized opioid dosage.

Implementation of an Enhanced Recovery Pathway for Minimally Invasive Pectus Surgery: A Population-Based Cohort Study Evaluating Short- and Long-Term Outcomes Using eHealth Technology.

BACKGROUND: Pectus excavatum and pectus carinatum are the most common chest wall deformities. Although minimally invasive correction (minimally invasive repair of pectus, MIRP) has become common practice, it remains associated with severe postoperative pain. Preoperative psychosocial factors such as anxiety and low self-esteem can increase postsurgical pain. Early detection of psychological symptoms, effective biopsychosocial perioperative management of patients, and prevention of pain chronification using an enhanced recovery pathway (ERP) may improve outcomes. However, the incidence of the latter is poorly described in adolescents undergoing MIRP. OBJECTIVE: The objective of our study was to evaluate the implementation of an ERP containing early recovery goals and to assess persistent postsurgical pain 3 months postoperatively in pediatric patients undergoing MIRP. The ERP consists of a Web-based platform containing psychological screening questionnaires and extensive telemonitoring for follow-up of patients at home. METHODS: A population-based cohort study was conducted with prospectively collected data from patients undergoing pectus surgery between June 2017 and December 2017. An ERP was initiated preoperatively; it included patient education, electronic health-based psychological screening, multimodal pre-emptive analgesia, nausea prophylaxis as well as early Foley catheter removal and respiratory exercises. After hospital discharge, patients were followed up to 10 weeks using a Web-based diary evaluating pain and sleep quality, while their rehabilitation progress was monitored via Bluetooth-connected telemonitoring devices. RESULTS: We enrolled 29 adolescents using the developed ERP. Pre-emptive multimodal analgesia pain rating scores were low at hospital admission. Optimal epidural placement, defined by T8-9 or T9-10, occurred in 90% (26/29) of the participants; thus, no motor block or Horner syndrome occurred. Mean bladder catheterization duration was 3.41 (SD 1.50) days in ERP patients. Numeric rating scale (NRS) scores for pain and the incidence of nausea were low, contributing to a fluent rehabilitation. Mean NRS scores were 2.58 (SD 1.77) on postoperative day (POD) 1, 2.48 (SD 1.66) on POD 2, and 3.14 (SD 1.98) on POD 3 in ERP-treated patients. Telemonitoring at home was feasible in adolescents after hospital discharge despite adherence difficulties. Although the pain scores at the final interview were low (0.81 [SD 1.33]), 33% (9/27) long-term follow-up ERP patients still experienced frequent disturbing thoracic pain, requiring analgesic administration, school absenteeism, and multiple doctor (re)visits. CONCLUSIONS: Allocating patients to the appropriate level of care preoperatively and immediately postoperatively may improve long-term outcome variables. Internet-based technologies and feasible, objective monitoring tools can help clinicians screen surgical patients for risk factors and initiate early treatment when indicated. Future research should focus on improving risk stratification and include a psychological assessment and evaluation of the effect of perioperative care pathways in children undergoing major surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03100669; https://clinicaltrials.gov/ct2/show/NCT03100669 (Archived by WebCite at http://www.webcitation.org/72qLB1ADX).

Diaphragmatic and intercostal electromyographic activity during neostigmine, sugammadex and neostigmine-sugammadex-enhanced recovery after neuromuscular blockade: A randomised controlled volunteer study.

BACKGROUND: Electromyographic activity of the diaphragm (EMGdi) during weaning from mechanical ventilation is increased after sugammadex compared with neostigmine. OBJECTIVE: To determine the effect of neostigmine on EMGdi and surface EMG (sEMG) of the intercostal muscles during antagonism of rocuronium block with neostigmine, sugammadex and neostigmine followed by sugammadex. DESIGN: Randomised, controlled, double-blind study. SETTING: Intensive care research unit. PARTICIPANTS: Eighteen male volunteers. INTERVENTIONS: A transoesophageal EMGdi recorder was inserted into three groups of six anaesthetised study participants, and sEMG was recorded on their intercostal muscles. To reverse rocuronium, volunteers received 50 µg kg neostigmine, 2 mg kg sugammadex or 50 µg kg neostigmine, followed 3 min later by 2 mg kg sugammadex. MAIN OUTCOME MEASURES: We examined the EMGdi and sEMG at the intercostal muscles during recovery enhanced by neostigmine or sugammadex or neostigmine-sugammadex as primary outcomes. Secondary objectives were the tidal volume, PaO2 recorded between the onset of spontaneous breathing and extubation of the trachea and SpO2 during and after anaesthesia. RESULTS: During weaning, median peak EMGdi was 0.76 (95% confidence interval: 1.20 to 1.80) µV in the neostigmine group, 1.00 (1.23 to 1.82) µV in the sugammadex group and 0.70 (0.91 to 1.21) µV in the neostigmine-sugammadex group (P < 0.0001 with EMGdi increased after sugammadex vs. neostigmine and neostigmine-sugammadex). The median peak intercostal sEMG for the neostigmine group was 0.39 (0.65 to 0.93) µV vs. 0.77 (1.15 to 1.51) µV in the sugammadex group and 0.82 (1.28 to 2.38) µV in the neostigmine-sugammadex group (P < 0.0001 with sEMG higher after sugammadex and after neostigmine-sugammadex vs. neostigmine). CONCLUSION: EMGdi and sEMG on the intercostal muscles were increased after sugammadex alone compared with neostigmine. Adding sugammadex after neostigmine reduced the EMGdi compared with sugammadex alone. Unlike the diaphragm, intercostal EMG was preserved with neostigmine followed by sugammadex. TRIAL REGISTRATION: EudraCT: 2015-001278-16; ClinicalTrials.gov: NCT02403063.

Number of sites of perinatal Candida colonization and neutropenia are associated with nosocomial candidemia in the neonatal intensive care unit patient.

OBJECTIVES: To determine the role of perinatally acquired Candida colonization to invasive Candida infection (candidemia) and to assess risk factors associated with Candida colonization and candidemia in neonatal intensive care unit patients. DESIGN: Retrospective case-control study. SETTING: Neonatal intensive care unit of a teaching hospital. PATIENTS: A total of 39 of 3219 (1.2%) who were positive for Candida colonization at birth were compared with 117 noncolonized controls. INTERVENTIONS: Routine surveillance cultures for Candida of skin and meconium were performed at admission. All neonates with Candida colonization at birth during a 10-yr period were identified. Each case was matched to place of birth and date of admission with three noncolonized controls. MEASUREMENTS AND MAIN RESULTS: Perinatal and neonatal variables were collected. Blood or skin culture was obtained when signs of sepsis or dermatitis were present. Patients with Candida colonization were compared with their noncolonized controls, whereas in this cohort, patients with candidemia were compared with those without by multivariate analysis. Vaginal candidiasis (odds ratio [OR] 15.8, 95% confidence interval [CI] 2.63, 94.77), birth weight below 1000 g (OR 8.1, 95% CI 1.22, 52.26), and vaginal delivery (OR 7.08, 95% CI 1.17, 42.70) were associated with Candida colonization. An increased risk for nosocomial candidemia was independently associated with the number of sites of Candida colonization (OR 24.02, 95% CI 1.89, 304), early neonatal neutropenia (OR 7.15, 95% CI 0.98, 80.95) and illness severity (clinical risk index for babies [CRIB]) score at day 1 (OR 1.38, 95%CI 1.065, 1.811). CONCLUSIONS: Maternal vaginal candidiasis and vaginal birth are risk factors for neonatal colonization. When controlling for illness severity, the number of sites colonized with Candida at birth contributes to neonatal nosocomial candidemia. Early neutropenia increases the risk further. These findings offer opportunities for prevention of Candida infection in neonatal intensive care unit patients.