The effectiveness of a transitional pain service in patients undergoing surgery with an increased risk of developing chronic postsurgical pain (TRUSt study). A randomized clinical trial.

STUDY OBJECTIVE: Poorly controlled acute postsurgical pain is associated with delayed recovery, chronic postsurgical pain (CPSP), chronic opioid use and impaired functioning in daily activities. The aim was to determine the effectiveness of a transitional pain service (TPS) to improve quality of recovery for patients at risk of CPSP. We hypothesized that a TPS improves the quality of recovery in patients at risk of CPSP. DESIGN: Single-center, pragmatic, randomized, superiority trial. SETTING: Tertiary hospital in the Netherlands. PATIENTS: Assessed for eligibility if ≥18 years of age, undergoing elective surgery, and had an increased risk of developing CPSP. After being stratified for sex, 176 patients were included. INTERVENTION: Patients were randomized to receive TPS or standard of care (SOC). TPS was a multidisciplinary intervention providing a patient-tailored perioperative pain management plan, throughout all phases of surgery. MEASUREMENTS: The primary outcome was the difference in quality of recovery on the third postoperative day, measured by the Quality of Recovery (QoR)-15 questionnaire. Secondary outcomes include the between group differences in opioid consumption. MAIN RESULTS: The primary outcome was available in 169 (96.0%) patients. No difference between groups was found in QoR-15 on the third postoperative day (mean difference 2.0, 95% CI -5.5 to 9.4, p = 0.607). A decrease in opioid usage (compared to baseline) was observed in chronic opioid users, the median [IQR] reduction in total daily oral morphine milligram equivalents (MME) for TPS was -30 [-60, 0] at three and - 29.3 [-65.6, 0] at six months, whereas SOC had a median reduction of 0 [-56, 0] at three, and 0 [-60, 7.5] at six months. CONCLUSIONS: TPS did not significantly affect short-term quality of recovery but might improve long-term outcomes, such as the incidence of chronic pain, opioid consumption, and functioning in daily life. However, sample size in the present study was too small to provide solid evidence for this positive signal.

Study protocol for the TRUSt trial: a pragmatic randomised controlled trial comparing the standard of care with a transitional pain service for patients at risk of chronic postsurgical pain undergoing surgery.

INTRODUCTION: Patients with either surgery-related or patient-related risk factors are at an increased risk of acute and chronic postsurgical pain (CPSP) and long-term opioid use. To improve recovery, prevent CPSP and decrease opioid use, we need to identify these patients before surgery and provide a multidisciplinary pain management strategy throughout hospital admission and follow-up in the postdischarge period. We hypothesise that a multidisciplinary transitional pain service (TPS) improves quality of recovery and reduce the incidence of CPSP and opioid consumption. METHODS AND ANALYSIS: We aim to investigate the effectiveness of implementation of a TPS for patients at risk of developing CPSP. The trial design is a pragmatic, open-label, randomised controlled trial (RCT). After stratification for sex, patients are randomly assigned to the TPS or standard of care (SOC) group. Our primary outcome is the quality of recovery, measured at the morning of the third postoperative day, employing the quality of recovery (QoR)-15 questionnaire. Secondary outcomes are the incidence of CPSP, opioid consumption and patient-reported outcome measures at 3 and 6 months postoperatively. We need to enrol 176 patients to detect a minimal clinical important difference of 8 points on the QoR-15 score. ETHICS AND DISSEMINATION: Ethics approval was obtained by the accredited medical research ethics committee of the Academic Medical Center in Amsterdam (2020_211) on 15 October 2020. Protocol version 3.2 was approved on 25 January 2020. The trial is registered with the Netherlands Trial Register, NL9115. The results will be disseminated by open access publication in a peer-reviewed journal.Trial registration number NL9115.

[Whether or not to use gabapentinoids in adults with chronic neuropathic pain]. / Wel of geen gabapentinoïden bij volwassenen met chronische neuropathische pijn?

CASE DESCRIPTION: A frail 85-year-old woman with chronic neuropathic pain after hip surgery, not responding to treatment with acetaminophen and morphine patches. Should she be prescribed a gabapentinoid? DISCUSSION: Gabapentinoids and antidepressants are considered first-line therapies. They achieve clinically relevant (i.e. ≥ 50%) pain reduction in approximately one-third of patients with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is limited. Adverse events occur frequently and are mostly mild in nature; serious adverse effects are rare. Prescription of gabapentinoids in specific patient groups (e.g. elderly patients and patients with a history of depression or substance abuse) deserves careful consideration, because the risk/benefit ratio in those groups may be altered. In order to reduce the risk of withdrawal symptoms, slow tapering is recommended. CONCLUSION: Chronic neuropathic pain often has a negative impact on the quality of life and is difficult to treat. In general, treatment with a gabapentinoid is a possible first-line treatment option. However, they may be relatively contraindicated in vulnerable patients.

Percutaneous fetoscopic patch closure of human spina bifida aperta: advances in fetal surgical techniques may obviate the need for early postnatal neurosurgical intervention.

BACKGROUND: A percutaneous minimally invasive fetoscopic approach was attempted for closure of a spina bifida aperta in two fetuses with L5 lesions. The goal was to obviate the need for postnatal neurosurgery to manage this condition. METHODS AND RESULTS: The percutaneous fetoscopic procedures were performed by a two-layer approach at respectively 22+/-2 and 22+/-4 weeks of gestation. The fetuses were delivered respectively at 32+/-6 and 32+3 weeks of gestation. Their neural cords were completely covered although in small areas skin closure was incomplete. Postnatally, complete skin closure occurred beneath an occlusive draping within 2 to 3 weeks such that neurosurgical intervention was not required. Both neonates showed reversal of hindbrain herniation, near-normal leg function, and satisfactory bladder and bowel function. For one of the two fetuses, ventriculoperitoneal shunt insertion was not required. CONCLUSIONS: Percutaneous minimally invasive fetoscopic patch closure of spina bifida aperta offers a substantially less maternal trauma than open fetal surgical repair and currently may even obviate the need for postnatal neurosurgical repair. With a little further improvement in surgical techniques and a better understanding of incorporating surgical patches into the fetus, complete skin closure seems possible in the near future.

Percutaneous fetoscopic laser decompression of congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia via a single trocar--current technical constraints and potential solutions for future interventions.

OBJECTIVE: To alleviate congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia by percutaneous minimally-invasive fetoscopic tracheal decompression using laser. METHODS: The procedure was performed via one trocar under general maternofetal anesthesia in a human fetus with CHAOS from laryngeal atresia at 21+6 weeks of gestation. RESULTS: Normalization of the lung-heart size relationship was observed within days after the procedure. The fetus was delivered by ex utero intrapartum treatment (EXIT) in order to perform a tracheotomy at 31+1 weeks of gestation and survived hospital treatment to discharge. CONCLUSIONS: Percutaneous minimally-invasive fetoscopic decompression of the fetal trachea via a single trocar is feasible in human fetuses with CHAOS from laryngeal atresia.

The efficacy of standard laxative use for the prevention and treatment of opioid induced constipation during oxycodone use: a small Dutch observational pilot study.

BACKGROUND: Dutch clinical guidelines recommend that a standard laxative treatment (SLT) should be prescribed concomitantly when starting opioid treatment to prevent opioid-induced constipation (OIC). METHODS: Clinical evidence for SLT in the treatment of OIC is lacking, therefore an observational pilot study was performed to explore the efficacy and tolerability of SLT on OIC in patients treated with the opioid oxycodone. RESULTS: Twenty-four patients (58% female, median (range) age 65 (39-92)) were included in this pilot study. The analysis showed that 9 out of 21 patients (43%) were non-responders to SLT. When also taking into consideration patients tending to develop diarrhea 75% of patients are non-responsive to SLT. CONCLUSION: This pilot study indicates that optimal laxative therapy (SLT) might not be effective and feasible for the prevention and treatment of OIC.

Single sodium channels from human skeletal muscle in planar lipid bilayers: characterization and response to pentobarbital.

PURPOSE: To investigate the response to general anesthetics of different sodium-channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human skeletal muscle and compared them to existing data from human brain and human ventricular muscle channels. METHODS: Sodium channels from a preparation of human skeletal muscle were incorporated into planar lipid bilayers, and the steady-state behavior of single sodium channels and their response to pentobarbital was examined in the presence of batrachotoxin, a sodium-channel activator. Single-channel currents were recorded before and after the addition of pentobarbital (0.34-1.34 mM). RESULTS: In symmetrical 500 mM NaCl, human skeletal muscle sodium channels had an averaged single-channel conductance of 21.0 +/- 0.6 pS, and the channel fractional open time was 0.96 +/- 0.04. The activation midpoint potential was -96.2 +/- 1.6 mV. Extracellular tetrodotoxin blocked the channel with a half-maximal concentration (k1/2) of 60 nM at 0 mV. Pentobarbital reduced the time-averaged conductance of single skeletal muscle sodium channels in a concentration-dependent manner (inhibitory concentration 50% [IC50] = 0.66 mM). The steady-state activation was shifted to more hyperpolarized potentials (-16.7 mV at 0.67 mM pentobarbital). CONCLUSION: In the planar lipid bilayer system, skeletal muscle sodium channels have some electrophysiological properties that are significantly different compared with those of sodium channels from cardiac or from central nervous tissue. In contrast to the control data, these different human sodium channel subtypes showed the same qualitative and quantitative response to the general anesthetic pentobarbital. The implication of these effects for overall anesthesia will depend on the role the individual channels play within their neuronal networks, but suppression of both central nervous system and peripheral sodium channels may add to general anesthetic effects.