Sedation and Analgesia for Reduction of Pediatric Ileocolic Intussusception.

Importance: Ileocolic intussusception is an important cause of intestinal obstruction in children. Reduction of ileocolic intussusception using air or fluid enema is the standard of care. This likely distressing procedure is usually performed without sedation or analgesia, but practice variation exists. Objective: To characterize the prevalence of opioid analgesia and sedation and assess their association with intestinal perforation and failed reduction. Design, Setting, and Participants: This cross-sectional study reviewed medical records of children aged 4 to 48 months with attempted reduction of ileocolic intussusception at 86 pediatric tertiary care institutions in 14 countries from January 2017 to December 2019. Of 3555 eligible medical records, 352 were excluded, and 3203 medical records were eligible. Data were analyzed in August 2022. Exposures: Reduction of ileocolic intussusception. Main outcomes and measures: The primary outcomes were opioid analgesia within 120 minutes of reduction based on the therapeutic window of IV morphine and sedation immediately before reduction of intussusception. Results: We included 3203 patients (median [IQR] age, 17 [9-27] months; 2054 of 3203 [64.1%] males). Opioid use was documented in 395 of 3134 patients (12.6%), sedation 334 of 3161 patients (10.6%), and opioids plus sedation in 178 of 3134 patients (5.7%). Perforation was uncommon and occurred in 13 of 3203 patients (0.4%). In the unadjusted analysis, opioids plus sedation (odds ratio [OR], 5.92; 95% CI, 1.28-27.42; P = .02) and a greater number of reduction attempts (OR, 1.48; 95% CI, 1.03-2.11; P = .03) were significantly associated with perforation. In the adjusted analysis, neither of these covariates remained significant. Reductions were successful in 2700 of 3184 attempts (84.8%). In the unadjusted analysis, younger age, no pain assessment at triage, opioids, longer duration of symptoms, hydrostatic enema, and gastrointestinal anomaly were significantly associated with failed reduction. In the adjusted analysis, only younger age (OR, 1.05 per month; 95% CI, 1.03-1.06 per month; P < .001), shorter duration of symptoms (OR, 0.96 per hour; 95% CI, 0.94-0.99 per hour; P = .002), and gastrointestinal anomaly (OR, 6.50; 95% CI, 2.04-20.64; P = .002) remained significant. Conclusions and Relevance: This cross-sectional study of pediatric ileocolic intussusception found that more than two-thirds of patients received neither analgesia nor sedation. Neither was associated with intestinal perforation or failed reduction, challenging the widespread practice of withholding analgesia and sedation for reduction of ileocolic intussusception in children.

Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain.

Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.

Effect of morphine added to multimodal cocktail on infiltration analgesia in total knee arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: The local injection of multimodal cocktail is currently commonly used in the treatment of postoperative pain after total knee arthroplasty (TKA). It is still inconclusive whether the morphine added to the intraoperative injection mixture could make some difference. This meta-analysis aimed to evaluate the efficacy and safety of additional morphine injection on postoperative analgesia in TKA, and provide some useful information on morphine usage in clinical practice. METHODS: The randomized controlled trials (RCTs) in databases including PubMed, Web of Science, Embase, Cochrane Library, Chinese biomedical literature database (CBM), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched. Of 623 records identified, 8 RCTs involving 1093 knees were eligible for data extraction and meta-analysis according to criteria included. RESULTS: Meta-analysis showed that the use of local morphine injection was not associated with significant pain relief within 48 hours postoperatively at rest and on motion (P > .05, all). The use of morphine reduced postoperative total systemic opioids consumption (P < .05). This study found no significant differences in other outcomes including knee flexion range of motion (ROM) (P > .05), extension ROM (P > .05), The Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores (P > .05), Post-operative nausea and vomiting occurrence (P > .05) regardless of the presence of morphine or not in the injections. CONCLUSION: Additional morphine added to multimodal cocktail did not decrease the postoperative pain scores significantly based on our outcomes, but it reduced the systemic postoperative opioids consumption in total knee arthroplasty.

Perinatal and neonatal use of sedation and analgesia.

Optimal obstetric and neonatal care requires the provision of adequate analgesia for painful procedures. However, anesthetic and analgesic agents have the potential to adversely impact the developing fetal/neonatal brain. In this setting, clinicians must assess the risks and benefits of pharmacologic anesthesia and analgesia for specific indications in this population. General anesthesia is required for non-obstetric surgery and cesarean section in the absence of neuraxial anesthesia for the health of the mother and fetus. Although experimental data raise concerns, human data are reassuring and future research may focus on neuroprotective adjuncts in the setting of repeated or prolonged anesthetic exposures. Opioid analgesia is standard of care for preterm infants undergoing major procedures including invasive surgery and endotracheal intubation. The use of opioids for agitation resulting from mechanical ventilation is controversial, but prevalent. Randomized and retrospective studies detect short-term toxicity with inconclusive long-term impact, suggesting the need to explore alternative therapies.

Codeine and opioid metabolism: implications and alternatives for pediatric pain management.

PURPOSE OF REVIEW: Use of perioperative opioids for surgical pain management of children presents clinical challenges because of concerns of serious adverse effects including life-threatening respiratory depression. This is especially true for children with history of obstructive sleep apnea. This review will explore current knowledge of clinically relevant factors and genetic polymorphisms that affect opioid metabolism and postoperative outcomes in children. RECENT FINDINGS: Within the past several years, an increasing number of case reports have illustrated clinically important respiratory depression, anoxic brain injuries and even death among children receiving appropriate weight-based dosages of codeine and other opioids for analgesia at home setting particularly following tonsillectomy. Several national and international organizations have issued advisories on use of codeine in pediatrics, based on cytochrome P450 family 2 subfamily D type 6 (CYP2D6) pharmacogenetics. We have discussed the pros and cons of alternatives to codeine for pain management. SUMMARY: Although routine preoperative genotyping to identify children at risk and personalized opioid use for pediatric perioperative pain management is still a distant reality, current known implications of CYP2D6 pharmacogenetics on codeine use shows that pharmacogenetics has the potential to guide anesthesia providers on perioperative opioid selection and dosing to maximize efficacy and safety.

Comparison of the analgesic efficacy of ultrasound-guided rectus sheath block and local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children.

BACKGROUND: Ultrasound-guided rectus sheath block and local anesthetic infiltration are the standard options to improve postoperative pain for children undergoing surgery with a midline incision. However, there is no study comparing the effect of ultrasound-guided rectus sheath block with local anesthetic infiltration for children undergoing laparoscopic surgery. AIMS: The aim of this trial was to compare the onset of ultrasound-guided rectus sheath block with that of local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children. METHODS: We performed an observer-blinded, randomized, prospective trial. Enrolled patients were assigned to either an ultrasound-guided rectus sheath block group or a local anesthetic infiltration group. The ultrasound-guided rectus sheath block group (n = 17) received ultrasound-guided rectus sheath block with 0.2 ml·kg-1 of 0.375% ropivacaine per side in the posterior rectus sheath compartment. The local anesthetic infiltration group (n = 17) received local anesthetic infiltration with 0.2 ml·kg-1 of 0.75% ropivacaine. The Face, Legs, Activity, Cry, and Consolability (FLACC) pain scores were recorded at 0, 30, 60 min after arrival at the postanesthesia care unit. RESULTS: Of the 37 patients enrolled in this study, 34 completed the study protocol. A significant difference in the pain scale between the ultrasound-guided rectus sheath block group and local anesthetic infiltration group was found at 0 min (median: 0, interquartile range [IQR]: 0-1.5, vs median: 1, IQR 0-5, confidence interval of median [95% CI]: 0-3, P = 0.048), but no significant difference was found at 30 min (median: 1, IQR: 0-4 vs median: 6, IQR: 0-7, 95% CI: 0-5, P = 0.061), or 60 min (median: 0, IQR: 0-2 vs median: 1, IQR: 0-3, 95% CI: -1 to 1, P = 0.310). No significant difference was found in anesthesia time between the ultrasound-guided rectus sheath block and local anesthetic infiltration groups. No procedure-related complications were observed in either group. CONCLUSION: Ultrasound-guided rectus sheath block is a quicker way to control postoperative pain for pediatric patients undergoing laparoscopic extraperitoneal closure than local anesthetic infiltration, and thus may provide a clinical benefit.

Infection Rates of Electrical Leads Used for Percutaneous Neurostimulation of the Peripheral Nervous System.

BACKGROUND: Percutaneous neurostimulation of the peripheral nervous system involves the insertion of a wire "lead" through an introducing needle to target a nerve/plexus or a motor point within a muscle. Electrical current may then be passed from an external generator through the skin via the lead for various therapeutic goals, including providing analgesia. With extended use of percutaneous leads sometimes greater than a month, infection is a concern. It was hypothesized that the infection rate of leads with a coiled design is lower than for leads with a noncoiled cylindrical design. METHODS: The literature was retrospectively reviewed for clinical studies of percutaneous neurostimulation of the peripheral nervous system of greater than 2 days that included explicit information on adverse events. The primary endpoint was the number of infections per 1,000 indwelling days. RESULTS: Forty-three studies were identified that met inclusion criteria involving coiled (n = 21) and noncoiled (n = 25) leads (3 studies involved both). The risk of infection with noncoiled leads was estimated to be 25 times greater than with coiled leads (95% confidence interval [CI] 2 to 407, P = 0.006). The infection rates were estimated to be 0.03 (95% CI 0.01 to 0.13) infections per 1,000 indwelling days for coiled leads and 0.83 (95% CI 0.16 to 4.33) infections per 1,000 indwelling days for noncoiled leads (P = 0.006). CONCLUSIONS: Percutaneous leads used for neurostimulation of the peripheral nervous system have a much lower risk of infection with a coiled design compared with noncoiled leads: approximately 1 infection for every 30,000 vs. 1,200 indwelling days, respectively.

In children undergoing umbilical hernia repair is rectus sheath block effective at reducing post-operative pain? Best evidence topic (bet).

A best evidence topic was constructed according to a structured protocol. The question addressed was: In children undergoing umbilical hernia repair is a rectus sheath block (RSB) better than local anaesthetic infiltration of the surgical site, at reducing post-operative pain? From a total of 34 papers, three studies provided the best available evidence on this topic. One randomised clinical trial showed RSB had a better analgesic effect in the immediate post-operative period. In another randomised trial opioid consumption in the peri-operative period was found to be significantly lower in patients administered RSB. These improvements in pain and analgesia consumption need to be balanced against the expertise, training, equipment required, time implications and complications of performing a RSB.

Topical lidocaine enhanced by laser pretreatment: a safe and effective method of analgesia for facial rejuvenation.

BACKGROUND: Injectable forms of anesthesia for nonsurgical facial rejuvenation, although efficacious, are uncomfortable for the patient. Preclinical studies have demonstrated that laser pretreatment at low energies enhances absorption of topical lidocaine. OBJECTIVES: The authors assess the safety and efficacy of laser-assisted transdermal delivery of topical anesthetic. METHOD: Ten patients were split into 2 groups (A and B). All patients received 15 g of BLT (20% benzocaine, 6% lidocaine, and 4% tetracaine triple anesthetic cream) for 20 minutes with no occlusion. Then the cream was removed and the first blood draw taken. Group A patients were pretreated with the full ablative laser and group B patients with a fractional ablative laser to the full face. A further 15 g BLT was applied for another 20 minutes. Group A patients then underwent full ablative laser treatment, and group B received fractionated ablative laser treatment. Blood draws were taken at 60, 90, 120, 180, and 240 minutes after the initial topical anesthetic application, and the serum was analyzed for lidocaine and monoethylglycinexylidide (MEGX) levels. Patients were asked to rate the pain felt at intervals during the procedure. RESULTS: No patient required supplemental nerve blocks. Pain scores were equivalent at the end of the first pass for both groups (P = .436). Group A patients had significantly lower pain scores at the start of the second laser treatment (P = .045), but pain scores became equivalent by the end (P = .323). Combined serum lidocaine and MEGX levels were significantly higher in group A patients up to 90 minutes (peak average of 0.61 µg/mL for group A and 0.533 µg/mL for group B; P = .0253), which corresponded to greater initial analgesic effect. CONCLUSIONS: Data from this study demonstrate that topical anesthetic for facial rejuvenation can be enhanced with laser pretreatment while maintaining safe blood serum levels. Further studies should examine optimal application amount and time to allow safe multipass facial rejuvenation without the need for invasive nerve blocks.

Reducing the pain: a systematic review of postdischarge analgesia following elective orthopedic surgery.

OBJECTIVE: This study aimed to determine which analgesic modalities used following discharge have the greatest efficacy in reducing postoperative pain after elective non-axial orthopedic surgery. DESIGN AND SETTING: A systematic review was conducted using the databases CENTRAL, MEDLINE, and EMBASE, as well as clinical practice guidelines databases and trial registries. Titles and abstracts were perused by two reviewers for randomized clinical trials in English fulfilling inclusion and exclusion criteria. Quality assessments, including the Oxford Quality Score, selective reporting, and sources of funding, were also performed. OUTCOME MEASURES: Pain intensity/relief, global patient evaluation, and use of rescue analgesia, as well as adverse events and withdrawals. RESULTS: 2,167 articles were retrieved and 23 articles were eligible for inclusion. They investigated analgesic modalities including alternative therapies (5); cyclooxygenase-2 inhibitors (3); nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) (12); opioids (2); and other pharmaceutical classes (1). Cycooxygenase-2 inhibitors and opioids demonstrated significant efficacy with minimal side effects. Most nonselective NSAIDs were effective analgesics but had a poorer side-effect profile. Alternative therapies demonstrated no significant efficacy. CONCLUSIONS: Opioids and cyclooxygenase-2 inhibitors are effective in providing analgesia in the extended postoperative period following orthopedic surgery with a minimal side-effect profile, while nonselective NSAIDs need to be treated with caution. Homeopathy is not an effective analgesic, while acupuncture has varied evidence and effectiveness. Treatment of postoperative fatigue may also improve analgesia control. This study provides orthopedic surgeons with a basis for evidence-based prescribing of postdischarge analgesia. However, further studies to validate these results against modern reporting standards are needed.

Neurotoxicity of adjuvants used in perineural anesthesia and analgesia in comparison with ropivacaine.

BACKGROUND AND OBJECTIVES: Clonidine, buprenorphine, dexamethasone, and midazolam (C, B, D, M) have been used to prolong perineural local anesthesia in the absence of data on the influence of these adjuvants on local anesthetic-induced neurotoxicity. Therefore, the impact of these adjuvants on ropivacaine (R)-induced death of isolated sensory neurons was assessed. METHODS: The trypan blue exclusion assay was used to assess death of sensory neurons isolated from adult male Sprague-Dawley rats. Drugs were applied, alone or in combination, for 2 or 24 hrs at 37°C. RESULTS: Neuronal viability was halved by 24-hr exposure to R (2.5 mg/mL), far exceeding the neurotoxicity of C, B, D, or M (at 2-100 times estimated clinical concentrations). Plain M at twice the estimated clinical concentration produced a small but significant increase in neurotoxicity at 24 hrs. After 2-hr exposure, high concentrations of B, C, and M increased the neurotoxicity of R; the combination of R + M killed more than 90% of neurons. Estimated clinical concentrations of C + B (plus 66 µg/mL D) had no influence on (i) R-induced neurotoxicity, (ii) the increased neurotoxicity associated with the combination of R + M, or (iii) the neurotoxicity associated with estimated clinical concentrations of M. There was increased neurotoxicity with 133 µg/mL D combined with R + C + B. CONCLUSIONS: Results with R reaffirm the need to identify ways to mitigate local anesthetic-induced neurotoxicity. While having no protective effect on R-induced neurotoxicity in vitro, future research with adjuvants should address if the C + B + D combination can enable reducing R concentrations needed to achieve equianalgesia (and/or provide equal or superior duration, in preclinical in vivo models).

Analgesia in fast-track paediatric cardiac patients.

OBJECTIVE: We introduced a fast-track program for our cardiac operations requiring adjustment in anaesthesia techniques to facilitate rapid extubation and discharge from the intensive care unit (ICU). Our objective was to investigate the quality of analgesia in fast-track paediatric cardiac patients. METHODS: We performed a retrospective review of the records of all patients who were fast-tracked in our institution between January 2006 and January 2007. Data collected included surgical procedure, anaesthesia technique, intra-operative opioids, ventilation time, intensive care stay, postoperative morphine consumption, pain scores, patient-controlled analgesia/nurse-controlled analgesia (PCA/NCA) duration, supplemental analgesia and incidence of vomiting. RESULTS: Fifty-four patients were studied, with a median age of 5.6 years (8 months-18 years), median weight 15.6 kg (range: 6.4-101 kg), median intensive care unit (ICU) ventilation time 1.1h (range: 0-8h) and median ICU stay of 4.1h (1-52 h). All patients received intra-operative fentanyl, median dose of 16.8 mcg kg⁻¹ (range: 15-20 mcg kg⁻¹). Twenty-three children received a bolus of morphine intra-operatively median dose of 102 mcg kg⁻¹ (range: 50-170 mcg kg⁻¹). Those patients who did not receive a morphine bolus intra-operatively, received a 100 mcg kg⁻¹ loading dose of morphine in the ICU. Twenty-four patients received intravenous paracetamol intra-operatively and five patients were given both paracetamol and diclofenac. Twenty-five children were not given either paracetamol or diclofenac intra-operatively. During the postoperative period, all patients received morphine by infusion administered via either PCA (18%) or NCA)(73%). The median PCA/NCA infusion time was 28.9h. Forty-eight patients received paracetamol and non-steroidal analgesics postoperatively, either diclofenac or ibuprofen. Five patients received only paracetamol and only one patient required no supplemental analgesia. The bedside nurse reported the pain scores on an hourly basis on a 10-point visual analogue score where 0=no pain and 10=strongest pain. Pain scores showed that most patients after day 0 (which was the day of surgery) had only mild pain. CONCLUSIONS: Our data showed that our program achieves high-quality analgesia in fast-track paediatric cardiac patients.

Multimodal analgesia in children.

Acute and chronic pain management in children is increasingly characterized by either a multimodal or a preventive analgesia approach, in which smaller doses of opioid and nonopioid analgesics, such as nonsteroidal anti-inflammatory drugs, local anaesthetics, N-methyl-D-aspartate antagonists, alpha(2)-adrenergic agonists, and voltage-gated calcium channel alpha-2 delta-proteins, are combined alone and in combination with opioids to maximize pain control and minimize drug-induced adverse side effects. A multimodal approach uses nonpharmacological complementary and alternative medicine therapies too. These include distraction, guided imagery, hypnosis, relaxation techniques, biofeedback, transcutaneous electrical nerve stimulation, and acupuncture. Using the neurophysiology of pain as a blueprint, the molecular targets and strategies used in multimodal pain management are described. Finally, weight-based dosage guidelines for commonly used opioid and nonopioid analgesics are provided to facilitate therapy.

Clinical efficacy of acupuncture on the morphine-related side effects in patients undergoing spinal-epidural anesthesia and analgesia.

OBJECTIVE: To investigate the effects of acupuncture on the morphine-related side effects (nausea, vomiting, itchiness and gastrointestinal disorders) in patients undergoing anesthesia and analgesia and try to find the clinical mechanism of acupuncture. METHODS: Patients scheduled to have transurethral prostatic resection: enrolled in the study (69 patients), characterized as Grade II or III by the American Society of Anesthesiologists physical status classification, were randomly assigned to three groups, 23 patients in each group: the placebo group (control group), non-anesthesia area (NAA) group, and the anesthesia area (AA) group. After spinal anesthesia, all patients received Patients Controlled Epidural Analgesia. The vital signs, bowel sounds, visual analogue scales, itchiness, nausea and vomiting, and time for first exhaust post operation were observed. RESULTS: Altogether, nine cases were eliminated, three in each group. Finally, sixty cases completed this study,: twenty in each group. There was a significant decrease of bowel sounds after morphine spinal anesthesia in the three groups. Compared with the control or AA group, the bowel sound recovered after acupuncture, the incidences of nausea and vomiting, itchiness, and time for first exhaust after operation decreased in the NAA group (P<0.05). There was a significant decrease of the incidence for itchiness in the NAA group compared with

Renal colic in adults: NSAIDs and morphine are effective for pain relief.

(1) Renal colic is an acute syndrome involving unilateral flank pain, linked to an obstruction in the upper urinary tract. The pain is often intense. After having considered other diagnoses and checked for signs of complication (fever, oligoanuria), the first step is to control the pain; (2) Which non-invasive treatments have a positive risk-benefit balance in relieving this type of pain? To answer this question, we reviewed the available evidence, based on the standard Prescrire methodology; (3) According to a meta-analysis of 20 trials, nonsteroidal antiinflammatory drugs (NSAIDs) and strong opioid analgesics have comparable efficacy. The most widely studied NSAID is diclofenac, given intramuscularly at a dose of 50 mg or 75 mg. Pethidine is the best-assessed strong opioid, given intramuscularly at a dose of 50 mg to 100 mg, which corresponds to about 5 mg to 10 mg of morphine. Morphine is given intravenously; subcutaneous administration is an alternative although it has not been evaluated in renal colic; (4) In clinical trials, NSAIDs were associated with fewer adverse effects than opioids, which cause vomiting in about 20% of patients (versus about 6% with an NSAID); (5) NSAIDs expose patients to a risk of functional renal impairment, especially in patients with heart failure, renal artery stenosis, dehydration, renal impairment or ongoing treatment with a nephrotoxic drug, and the very elderly. NSAIDs should never be used during pregnancy; (6) According to one trial in 130 patients, the analgesic effect of the morphine and NSAID combination was greater than either agent used alone, in about 10% of patients; (7) Paracetamol has not been evaluated in comparative trials of renal colic, even for moderate pain; (8) Scopolamine is the only antispasmodic to have been evaluated in a comparative trial. Adding scopolamine to morphine did not seem to provide additional efficacy; (9) Other drugs, which have not been adequately tested as of early 2009, have no documented benefit in the treatment of the pain associated with renal colic; tamsulosin, nifedipine, desmopressin; (10) Among the non-drug measures tested, local active warming, taking care to avoid burns, was effective against pain according to one trial; pain was reduced by at least 50% using a device delivering 42 degrees C to the abdomen or lower back; (11) In pregnant women, morphine carries a lower risk of adverse effects than NSAIDs; (12) In practice, the treatment of renal colic is mainly based on taking an NSAID, or morphine when the NSAID does not adequately control the pain or when it is better to avoid using NSAIDs.