Lateness of Acetaminophen and Non-steroidal Anti-inflammatory Drug Administrations in a Retrospective Cohort of Medication Administration Records Among Patients After Cesarean Delivery.

INTRODUCTION: In an earlier study of patients after cesarean delivery, the concurrent versus alternating administration of acetaminophen and non-steroidal anti-inflammatory drugs was associated with a substantial reduction in total postoperative opioid use. This likely pharmacodynamic effect may differ if the times when nurses administer acetaminophen and non-steroidal anti-inflammatory drugs often differ substantively from when they are due. We examined the "lateness" of analgesic dose administration times, the positive difference if administered late, and the negative value if early. METHODS: The retrospective cohort study used all 67,900 medication administration records for scheduled (i.e., not "as needed") acetaminophen, ibuprofen, and ketorolac among all 3,163 cesarean delivery cases at the University of Iowa between January 2021 and December 2023. Barcode scanning at the patient's bedside was used right before each medication administration. RESULTS: There were 95% of doses administered over a 4.8-hour window, from 108 minutes early (97.5% one-sided upper confidence limit 105 minutes early) to 181 minutes late (97.5% one-sided lower limit 179 minutes late). Fewer than half of doses (46%, P <0.0001) were administered ±30 minutes of the due time. The intraclass correlation coefficient was approximately 0.11, showing that there were small systematic differences among patients. There likewise were small to no systematic differences in lateness based on concurrent administrations of acetaminophen and ibuprofen or ketorolac, time of the day that medications were due, weekday, year, or number of medications to be administered among all such patients within 15 minutes. DISCUSSION: Other hospitals should check the lateness of medication administration when that would change their ability to perform or apply the results of analgesic clinical trials (e.g., simultaneous versus alternating administration).

CPL-01, an investigational long-acting ropivacaine, demonstrates safety and efficacy in open inguinal hernia repair.

BACKGROUND: There is an unmet medical need for effective nonopioid analgesics that can decrease pain while reducing systemic opioid use. CPL-01, an extended-release injectable formulation of ropivacaine, is designed to safely provide analgesia and reduce or eliminate opioid use in the postoperative period. METHODS: Subjects undergoing open inguinal hernia with mesh were prospectively randomized to 1 of 3 doses of CPL-01 (10, 20, or 30 ml of 2% CPL-01, n = 14, 12, and 14, respectively), Naropin (150 mg, n = 40), or saline placebo (n = 13) infiltrated into the surgical site prior to closure. Pain and rescue medication usage was assessed, and Numeric Rating Scale (NRS) pain scores were adjusted for opioid usage using windowed worst observation carried forward (wWOCF) imputation. The primary efficacy endpoint was the mean area under the curve (AUC) of the NRS pain intensity scores with activity. RESULTS: Ninety-three subjects were treated, and 91 subjects completed 72 h of post-operative monitoring. Subjects who received the highest dose of CPL-01 in Cohort 3 showed a clinically meaningful reduction in postoperative pain intensity scores, which was the lowest value for any treatment in all cohorts, showing a trend towards statistical significance as compared to the pooled placebo group (p = 0.08), and numerically better than the 40 subjects who received Naropin. Opioid use through 72 h in subjects who received CPL-01 in Cohort 3 was approximately half of that shown in the placebo and Naropin groups; approximately 2/3 of the CPL-01 subjects (9/14) required no opioids at all through the first 72 h after the operation. More CPL-01 subjects avoided severe pain and were ready for discharge earlier than other groups. CPL-01 was safe and well-tolerated, with no clinically meaningful safety signals, and showed predictable and consistent extended-release pharmacokinetics. CONCLUSION: Results suggest that CPL-01 may be the first long-acting ropivacaine to address postoperative pain while reducing the need for opioids.

rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.

Chronic pain is common and inadequately treated, making the development of safe and effective analgesics a high priority. Our previous data indicate that carbonic anhydrase-8 (CA8) expression in dorsal root ganglia (DRG) mediates analgesia via inhibition of neuronal ER inositol trisphosphate receptor-1 (ITPR1) via subsequent decrease in ER calcium release and reduction of cytoplasmic free calcium, essential to the regulation of neuronal excitability. This study tested the hypothesis that novel JDNI8 replication-defective herpes simplex-1 viral vectors (rdHSV) carrying a CA8 transgene (vHCA8) reduce primary afferent neuronal excitability. Whole-cell current clamp recordings in small DRG neurons showed that vHCA8 transduction caused prolongation of their afterhyperpolarization (AHP), an essential regulator of neuronal excitability. This AHP prolongation was completely reversed by the specific Kv7 channel inhibitor XE-991. Voltage clamp recordings indicate an effect via Kv7 channels in vHCA8-infected small DRG neurons. These data demonstrate for the first time that vHCA8 produces Kv7 channel activation, which decreases neuronal excitability in nociceptors. This suppression of excitability may translate in vivo as non-opioid dependent behavioral- or clinical analgesia, if proven behaviorally and clinically.

Sex Differences in Opioid Administration After Cardiac Surgery.

OBJECTIVES: To assess whether there are sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: At a tertiary academic referral center. PARTICIPANTS: Adult patients who underwent cardiac surgery from 2014 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the cumulative oral morphine equivalent dose (OMED) for the postoperative admission. Secondary outcomes were the daily difference in OMED and the administration of nonopioid analgesics. The authors developed multivariate regression models controlling for known confounders, including weight and length of stay. A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% CI, -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (odds ratio, 1.91; 95% CI, 1.42-2.58; p < 0.001). The authors found no association between patient sex and the administration of other nonopioid analgesics or specific types of opioid analgesics. The authors found no association between patient sex and pain scores recorded within the first 48 hours after extubation, or the number of opioids administered in close proximity to pain assessments. CONCLUSIONS: Female sex was associated with significantly lower amounts of opioids administered after cardiac surgery.

Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series.

Purpose: Low-dose naltrexone (LDN) has increased in popularity as a non-opioid medication that may decrease chronic pain symptoms. LDN is most commonly used to treat fibromyalgia, complex regional pain syndrome (CRPS), and painful diabetic neuropathy. Other studies suggest that LDN provides general symptom reduction in inflammatory conditions such as Crohn's disease and multiple sclerosis. We reviewed our experience with patients to whom we have prescribed LDN to see what types of painful conditions were most responsive to LDN in our patient population. Patients and Methods: Charts from patients who came to the Pain Center between 2014 and 2021 were reviewed. Results: Of the n = 137 patients who were prescribed LDN, 44% had no evidence of ever filling the prescription, and 4.4% of the responses were not charted. Of the remaining who took LDN (n = 70), 64% had some relief and were designated as 'Responders'. The most common pain diagnosis was neuropathic pain which, when added to the diagnosis of complex regional pain syndrome, accounted for 51% of responders to LDN. Patients who experienced greater than 50% pain relief from LDN were more likely to have the diagnosis of neuropathic pain or complex regional pain syndrome (p = 0.038, Fisher's Exact Test). There was a significant difference in the diagnosis of patients who responded to LDN. Patients with spondylosis were much less likely to respond to LDN when compared with other diagnoses (p = 0.00435, Chi-Square Test). Conclusion: Patients with all types of neuropathic pain, including CRPS, were significantly more likely to have pain relief from LDN than patients with spondylosis (p=0.018). The diagnosis of spondylosis was more often associated with a lack of response to LDN than any other diagnosis. Patients may need to have a trial of several weeks before analgesic effects are seen with LDN.

Comparative Efficacy of Adjuvant Nonopioid Analgesia in Adult Cardiac Surgical Patients: A Network Meta-Analysis.

OBJECTIVES: To compare the relative efficacy of adjuvant nonopioid analgesic regimens in adult cardiac surgical patients. DESIGN: This frequentist, random-effects network meta-analysis (NMA) was prospectively registered on PROSPERO (CRD42021282913) and conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA). The risk of bias (RoB) and confidence of evidence were assessed by RoB 2 and Confidence in Network Meta-Analysis, respectively. Relevant databases were searched from inception to October 9, 2021. SETTING: A total of 124 (N = 26,257) randomized controlled trials were included, of which 110 were analyzed. PARTICIPANTS: Trials enrolling adults (≥18 years of age) undergoing cardiac surgery that compared nonopioid analgesics against other nonopioid analgesics, placebo, or no additional treatment, as adjuvants to standard analgesic management, and reported at least 1 of the outcomes of interest. MEASUREMENT AND MAIN RESULTS: Outcomes of interest included resting postoperative pain scores at 24 hours. Compared with standard care and/or placebo, pain scores were reduced significantly by 10 different regimens, including acetaminophen (N = 176; mean difference [MD] -0.66 points, 95% CI -1.16 to -0.15 points; high confidence), magnesium (N = 323; -0.05 points, 95% CI -0.07 to -0.02 points; high confidence), gabapentin (N = 96; MD -0.40 points, 95% CI -0.71 to -0.09; moderate confidence), and clonidine (N = 64; MD v0.38 points, 95% CI -0.73 to v0.04 points; moderate confidence). Indomethacin, diclofenac, magnesium, and gabapentin significantly reduced 24-hour opioid consumption. Four regimens significantly decreased the intensive care unit length of stay. Hydrocortisone, dexmedetomidine, and clonidine significantly decreased the duration of mechanical ventilation. Magnesium decreased, while methylprednisolone significantly increased, the risk of myocardial infarction. CONCLUSIONS: Given the increasing emphasis on enhanced recovery after surgery(ERAS) protocols and the eventual goal of limiting opiate prescriptions postoperatively, the authors' data suggested far greater use of nonopioid adjuncts to minimize pain and enhance recovery following cardiac surgery.

Neural and molecular investigation into the paraventricular thalamic-nucleus accumbens circuit for pain sensation and non-opioid analgesia.

The paucity of medications with novel mechanisms for pain treatment combined with the severe adverse effects of opioid analgesics has led to an imperative pursuit of non-opioid analgesia and a better understanding of pain mechanisms. Here, we identify the putative glutamatergic inputs from the paraventricular thalamic nucleus to the nucleus accumbens (PVTGlut→NAc) as a novel neural circuit for pain sensation and non-opioid analgesia. Our in vivo fiber photometry and in vitro electrophysiology experiments found that PVTGlut→NAc neuronal activity increased in response to acute thermal/mechanical stimuli and persistent inflammatory pain. Direct optogenetic activation of these neurons in the PVT or their terminals in the NAc induced pain-like behaviors. Conversely, inhibition of PVTGlut→NAc neurons or their NAc terminals exhibited a potent analgesic effect in both naïve and pathological pain mice, which could not be prevented by pretreatment of naloxone, an opioid receptor antagonist. Anterograde trans-synaptic optogenetic experiments consistently demonstrated that the PVTGlut→NAc circuit bi-directionally modulates pain behaviors. Furthermore, circuit-specific molecular profiling and pharmacological studies revealed dopamine receptor 3 as a candidate target for pain modulation and non-opioid analgesic development. Taken together, these findings provide a previously unknown neural circuit for pain sensation and non-opioid analgesia and a valuable molecular target for developing future safer medication.

Non-opioid analgesics for the prevention of chronic postsurgical pain: a systematic review and network meta-analysis.

BACKGROUND: Chronic postsurgical pain is common after surgery. Identification of non-opioid analgesics with potential for preventing chronic postsurgical pain is important, although trials are often underpowered. Network meta-analysis offers an opportunity to improve power and to identify the most promising therapy for clinical use and future studies. METHODS: We conducted a PRISMA-NMA-compliant systematic review and network meta-analysis of randomised controlled trials of non-opioid analgesics for chronic postsurgical pain. Outcomes included incidence and severity of chronic postsurgical pain, serious adverse events, and chronic opioid use. RESULTS: We included 132 randomised controlled trials with 23 902 participants. In order of efficacy, i.v. lidocaine (odds ratio [OR] 0.32; 95% credible interval [CrI] 0.17-0.58), ketamine (OR 0.64; 95% CrI 0.44-0.92), gabapentinoids (OR 0.67; 95% CrI 0.47-0.92), and possibly dexmedetomidine (OR 0.36; 95% CrI 0.12-1.00) reduced the incidence of chronic postsurgical pain at ≤6 months. There was little available evidence for chronic postsurgical pain at >6 months, combinations agents, chronic opioid use, and serious adverse events. Variable baseline risk was identified as a potential violation to the network meta-analysis transitivity assumption, so results are reported from a fixed value of this, with analgesics more effective at higher baseline risk. The confidence in these findings was low because of problems with risk of bias and imprecision. CONCLUSIONS: Lidocaine (most effective), ketamine, and gabapentinoids could be effective in reducing chronic postsurgical pain ≤6 months although confidence is low. Moreover, variable baseline risk might violate transitivity in network meta-analysis of analgesics; this recommends use of our methods in future network meta-analyses. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021269642.

Opioid versus non-opioid analgesia for spine surgery: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Opioids are the primary analgesics used in patients undergoing spine surgery. Postoperative pain is common despite their liberal use and so are opioid-associated side effects. Non-opioid analgesics are gaining popularity as alternative to opioids in spine surgery. METHODS: This systematic review evaluated current evidence regarding opioid and non-opioid intraoperative analgesia and their influence on immediate postoperative pain and adverse events in spine surgery. RESULTS: A total of 10,459 records were obtained by searching Medline, EMBASE and Web of Science databases and six randomized controlled trials were included. Differences in postoperative pain scores between opioid and non-opioid groups were not significant at 1 h: 4 studies, mean difference (MD) = 0.65 units, 95% confidence intervals (CI) [-0.12 to 1.41], p = 0.10, but favored non-opioid at 24 h after surgery: 3 studies, MD = 0.75 units, 95%CI [0.03 to 1.46], p = 0.04. The time for first postoperative analgesic requirement was shorter (MD = -45.06 min, 95%CI [-72.50 to -17.62], p = 0.001), and morphine consumption during first 24 h after surgery was higher in opioid compared to non-opioid group (MD = 4.54 mg, 95%CI [3.26 to 5.82], p < 0.00001). Adverse effects of postoperative nausea and vomiting (Relative risk (RR) = 2.15, 95%CI [1.37 to 3.38], p = 0.0009) and shivering (RR = 2.52, 95%CI [1.08 to 5.89], p = 0.03) were higher and bradycardia was lower (RR = 0.35, 95%CI [0.17 to 0.71], p = 0.004) with opioid analgesia. CONCLUSION: The certainty of evidence on GRADE assessment is low for studied outcomes. Available evidence supports intraoperative non-opioid analgesia for overall postoperative pain outcomes in spine surgery. More research is needed to find the best drug combination and dosing regimen. Prospero Registration: CRD42020209042.

National Intravenous Acetaminophen Use in Pediatric Inpatients From 2011-2016.

OBJECTIVE: To 1) determine current intravenous (IV) acetaminophen use in pediatric inpatients; and 2) determine the association between opioid medication duration when used with or without IV acetaminophen. METHODS: A retrospective analysis of pediatric inpatients exposed to IV acetaminophen from January 2011 to June 2016, using the national database Health Facts. RESULTS: Eighteen thousand one hundred ninety-seven (2.0%) of 893,293 pediatric inpatients received IV acetaminophen for a median of 14 doses per patient (IQR, 8-56). A greater proportion of IV acetaminophen patients were admitted to the intensive care unit (ICU) (14.8% vs 5.1%, p < 0.0001), received positive pressure ventilation (2.0% vs 1.5%, p < 0.0001), had a higher hospital mortality rate (0.9% vs 0.3%, p < 0.0001), and were operative (35.5% vs 12.8%, p < 0.001) than those not receiving IV acetaminophen. The most common operations associated with IV acetaminophen use were musculoskeletal and digestive system operations. Prescription of IV acetaminophen increased over time, both in prescription rates and number of per patient doses. Of the 18,197 patients prescribed IV acetaminophen, 16,241 (89.2%) also were prescribed opioids during their hospitalization. A multivariate analysis revealed patients prescribed both IV acetaminophen and opioids had a 54.8% increase in opioid duration as compared with patients who received opioids alone. CONCLUSIONS: This is the first study to assess IV acetaminophen prescription practices for pediatric inpatients. Intravenous acetaminophen prescription was greater in the non-operative pediatric inpatient population than operative patients. Intravenous acetaminophen prescription was associated with an increase in opioid duration as compared with patients who received opioids alone, suggesting that it is commonly used to supplement opioids for pain relief.

Moving Toward a Multimodal Analgesic Regimen for Acute Sickle Cell Pain with Non-Opioid Analgesic Adjuncts: A Narrative Review.

Purpose of Review: Sickle cell disease (SCD) is an inherited hemoglobinopathy with potential life-threatening complications that affect millions of people worldwide. Severe and disabling acute pain, referred to as a vaso-occlusive crisis (VOC), is a fundamental symptom of the disease and the primary driver for acute care visits and hospitalizations. Despite the publication of guidelines for VOC management over the past decade, management of VOCs remains unsatisfactory for patients and providers. Recent Findings: Acute SCD pain includes pain secondary to VOCs and other forms of acute pain. Distinguishing VOC from non-VOC pain may be challenging for both patients and clinicians. Further, although opioids have been the gold-standard for VOC pain management for decades, the current highest standard of care for all acute pain is a multimodal approach that is less dependent on opioids, and, instead incorporates analgesics and adjuvants from different mechanistic pathways. In this narrative review, we focus on a multimodal pharmacologic approach for acute SCD pain management and explore the evidence for existing non-opioid pharmacological adjuncts. Moreover, we present an explanatory model of pain, which is not only novel in its application to SCD pain but also captures the multidimensional nature of the SCD pain experience and supports the need for such a multimodal approach. This model also highlights opportunities for new investigative and therapeutic targets - both pharmacological and non-pharmacological. Summary: Multimodal pain regimens that are less dependent on opioids are urgently needed to improve acute pain outcomes for individuals with SCD. The proposed explanatory model for SCD pain offers novel opportunities to improve acute pain management for SCD patients.

A standardized post-cesarean analgesia regimen reduces postpartum opioid use.

BACKGROUND: Optimal post-cesarean pain control is important. With the rising opioid epidemic it is imperative to maximize non-opioid based primary approaches to post-cesarean pain control. In 2018, we implemented a standardized post-cesarean analgesia regimen. OBJECTIVE: To determine if implementation of a standardized postoperative analgesic regimen decreases opioid use following cesarean birth. STUDY DESIGN: A standardized postoperative analgesia protocol was implemented in June 2018, which included scheduled oral acetaminophen (975 mg every 6 h) and nonsteroidal anti-inflammatory drugs (NSAIDs) (ketorolac 15 mg IV every 6 h for 5 doses followed by ibuprofen 600 mg oral every 6 h) with opioids available for breakthrough pain. There was no prior standardized protocol. A before-and-after study design was used to compare oral morphine milligram equivalents (MME) for nine months prior to and nine months after this protocol was implemented, excluding the two month period of protocol rollout. Women with opioid use disorder or postoperative intubation were excluded. The primary outcome was the cumulative MME used in the first 72 h postoperatively. Total dose at 12, 24, and 48 h were also compared. RESULTS: Of 2340 women who underwent cesarean birth during the study period (1 July 2017 - 30 April 2019), 2001 women met inclusion criteria (914 before 10 April 2018 (pre-protocol) and 1087 after 17 June 2018 (post-protocol)). Baseline characteristics of the two groups were similar, including gestational age at delivery, maternal body mass index (BMI), planned versus unplanned cesarean birth, and type of intraoperative anesthesia used. The cumulative opioid dose in the first 72 h postoperatively was 216.3 ± 84.3 MME prior to implementation compared to 171.5 ± 91.5 MME following implementation (p < .001). The average cumulative MME use was higher in the pre-protocol period compared to post-protocol at all time periods: 12 h (57.3 ± 23.8 vs 48.6 ± 26.2 MME, p < .001), 24 h (98.1 ± 34.1 vs 82.1 ± 38.8 MME, p < .001), and 48 h (165.8 ± 58.3 vs 134.9 ± 66.2 MME, p < .001). The average pain scores were lower in the pre-protocol group (3 vs 3.3, p < .001). CONCLUSION: Scheduled administration of acetaminophen and NSAIDs following cesarean birth significantly decreased the cumulative dose of opioids used in the first 72 h postoperatively.

Regional Analgesia for Cardiac Surgery Part 1. Current status of neuraxial and paravertebral blocks for adult cardiac surgery.

Cardiac surgeries are known to produce moderate to severe pain. Pain management has traditionally been based on intravenous opioids. Poorly controlled pain can result in increased incidence of respiratory complications such as atelectasis and pneumonia leading to prolonged intubation and intensive care unit length of stay and subsequent prolonged hospital stay. Adequate perioperative analgesia improves hemodynamics and immunologic responses, which would result in better outcomes after cardiac surgery. Opioid sparing "Enhanced Recovery After Surgery" protocols are increasingly being incorporated into cardiac surgeries. This will reduce opioid requirements and opioid-related side effects and facilitate fast-tracking of patients. Regional analgesia can be provided by neuraxial blocks, fascial plane blocks, peripheral nerve blocks, or simply by the infiltration of the wound with local anesthetics for cardiac surgery. Neuraxial analgesia is provided through epidural, spinal, and paravertebral routes. Though they are being replaced by peripheral fascial plane blocks, epidural and spinal analgesia are still being used in some centers. In this article, neuraxial forms of analgesia are focused. We sought to review epidural analgesia and its impact in suppressing hemodynamic stress response, reducing pulmonary complications, and development of chronic pain. The relationship between intraoperative heparinization and potential neuraxial hematoma is discussed. Other neuraxial options such as spinal and paravertebral analgesia and their usefulness, benefits, and limitations are also reviewed.

Effect of Opioid Versus Non-Opioid Analgesia on Surgical Pleth Index and Biomarkers of Surgical Stress During Neurosurgery for Brain Tumors: Preliminary Findings.

BACKGROUND: Stress response to surgery is mediated by the sympathetic nervous system and manifests as changes in hemodynamic and neuroendocrine parameters. Recently, the surgical pleth index (SPI) is employed for objective and continuous monitoring of nociceptive response during surgery. Opioids are the mainstay of managing stress response to nociception during the perioperative period. However, due to the well-known adverse effects of opioids, α2 agonists are increasingly used to ablate stress response and reduce opioid usage. OBJECTIVES: This study compared SPI and biomarkers of surgical stress between opioid (fentanyl) and non-opioid (dexmedetomidine) analgesia during craniotomy. METHODS: Patients aged 18 to 60 years undergoing elective craniotomies for brain tumor resection under general anesthesia were randomized to receive fentanyl 1 µg/kg/h or dexmedetomidine 0.5 µ/kg/h infusion as the primary intraoperative analgesic. Our objective was to compare SPI and biomarkers of surgical stress-serum cortisol, blood glucose, arterial pH, and leucocyte count between the two groups. RESULTS: Data of all 24 patients recruited into the study were analyzed. There was no difference in the demographic parameters between the groups. The SPI remained similar with both the drugs over various time points during the study period. There was no difference between the groups in the biomarkers of surgical stress-cortisol, blood glucose, and pH while leucocyte count was higher in the fentanyl group. CONCLUSIONS: The stress response to surgery during craniotomy for brain tumors is similar with opioid (fentanyl) and non-opioid (dexmedetomidine) analgesia as assessed by SPI and blood markers such as cortisol, glucose, and pH.

Analgésicos no opioides / Non-opioid analgesics

Resumen La analgesia multimodal es una recomendación universal para el control del dolor postoperatorio en situaciones clínicas diversas. Esta recomendación está avalada por la Sociedad Americana del Dolor (APS), la Sociedad Americana de Anestesia Regional y Medicina del Dolor (ASRA) y la Sociedad Americana de Anestesiólogos (ASA). La terapia analgésica multimodal se individualiza y ajusta de acuerdo con la edad, el tipo de dolor e intensidad, el procedimiento quirúrgico específico, las morbilidades asociadas y los efectos adversos de los fármacos. La escalera analgésica propuesta por la Organización Mundial de la Salud fue adaptada por la Federación Mundial de Sociedades y Asociaciones de Anestesiólogos (1997) para el abordaje del dolor agudo perioperatorio. Los analgésicos no opioides son la piedra angular para una terapia perioperatoria exitosa; entre los cuales se encuentran el paracetamol, los antiinflamatorios no esteroideos no selectivos y los COX-2, así como los coadyuvantes (para ver el artículo completo visite http://www.painoutmexico.com).

Abstract: Multimodal analgesia is an universal recommendation for the control of postoperative pain in diverse clinical situations. This recommendation is endorsed by the American Pain Society (APS), the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the American Society of Anesthesiologists (ASA). Multimodal analgesic therapy is individualized and adjusted according to age, type of pain and intensity, specific surgical procedure, associated morbidities and adverse effects of drugs. The analgesic ladder proposed by the World Health Organization was adapted by the World Federation of Societies and Associations of Anesthesiologists (1997) for the management of acute perioperative pain. Non-opioid analgesics are the cornerstone for a successful perioperative therapy, among which are paracetamol, non-selective and COX-2, also include adjuvants (full version visithttp://www.painoutmexico.com ).

Opioid-Free Analgesia for Supratentorial Craniotomies: A Systematic Review.

BACKGROUND: Post-craniotomy pain can be severe and is often undermanaged. Opioids can interfere with neurological monitoring and are associated with adverse effects. This systematic review aimed to identify measures of opioid-free analgesia and compare their effectiveness with opioid analgesia for post-craniotomy pain in patients with supratentorial tumors. METHODS: EMBASE, MEDLINE, and Cochrane databases were searched from their inception to February 14, 2017, for randomized controlled trials (RCTs) evaluating opioid versus non-opioid analgesia post-supratentorial craniotomy. Two reviewers independently carried out study selection and data extraction. Risk of bias assessment was performed using the Cochrane Collaboration's tool. Outcomes were pain control (changes to pain scores or use of rescue analgesia) and adverse effects. Considering the number of studies and heterogeneity, a narrative synthesis was done without pooling and results were summarized using tables. Non-opioids were assessed for the potential to be equivalent to opioid-based analgesics for pain relief and adverse effects. RESULTS: Of 467 RCTs, 4 met our inclusion criteria (n = 186 patients). Patients with scalp blocks (2 RCTs) had less post-operative nausea and vomiting (PONV), but scalp block was not superior to morphine for analgesia. Acetaminophen (1 RCT) was less likely to induce PONV but provided inadequate pain relief compared to morphine and sufentanil. Dexmedetomidine (1 RCT) was not superior to remifentanil for analgesia although it delayed time to rescue analgesia. CONCLUSIONS: Limited evidence suggests that scalp blocks and dexmedetomidine have the potential to eliminate the need for opioid analgesia. Multimodal analgesia should be considered as significant opioid-sparing effects have been shown.

Analgésie sans opioïdes dans les craniotomies supratentorielles: revue systématique. Contexte: La douleur post-craniotomie peut être sévère et n'est souvent pas maintenue. Les opioïdes peuvent interférer avec la surveillance neurologique et sont associés à des effets indésirables. Cette revue systématique visait à identifier les mesures d'analgésie sans opioïdes et à comparer leur efficacité à celle des analgésiques opioïdes pour le traitement de la douleur post-craniotomie chez les patients atteints de tumeurs supratentorielles. Méthodes: Les bases de données EMBASE, MEDLINE et Cochrane ont été explorées depuis leur création jusqu'au 14 février 2017 dans le cadre d'essais contrôlés randomisés (ECR) évaluant l'analgésie opioïde ou non opioïde après la craniotomie supratentorielle. Deux examinateurs ont indépendamment sélectionné les études et extrait les données. L'évaluation du risque de biais a été réalisée à l'aide de l'outil Cochrane Collaboration. Les résultats ont été un contrôle de la douleur (modification des scores de douleur ou l'utilisation d'une analgésie de secours) et des effets indésirables. Compte tenu du nombre d'études et de l'hétérogénéité, une synthèse narrative a été réalisée sans regroupement et les résultats ont été résumés à l'aide de tableaux. Les non-opioïdes ont été évalués pour leur potentiel équivalent aux analgésiques à base d'opioïdes pour le soulagement de la douleur et les effets indésirables. Résultats: Sur 467 ECR, 4 répondaient à nos critères d'inclusion (n = 186 patients). Les patients avec des blocs de cuir chevelu 14 (2 ECR) avaient moins de nausées et de vomissements postopératoires (NVPO), mais le bloc de cuir chevelu n'était pas supérieur à la morphine pour l'analgésie. L'acétaminophène (1 ECR) était moins susceptible d'induire des NVPO, mais ne soulageait pas suffisamment la douleur par rapport à la morphine et au sufentanil. La dexmédétomidine (1 ECR) n'était pas supérieure au rémifentanil pour l'analgésie, bien qu'elle ait retardé le délai de récupération de l'analgésie. Conclusions: Des preuves limitées suggèrent que les blocs du cuir chevelu et la dexmédétomidine pourraient éliminer le besoin d'une analgésie opioïde. Une analgésie multimodale doit être considérée, car des effets importants, qui permettent d'épargner les opioïdes, ont été démontrés.

World Workshop on Oral Medicine VII: Non-opioid pain management of head and neck chemo/radiation-induced mucositis: A systematic review.

OBJECTIVE: To evaluate the current evidence regarding the effectiveness of non-opioid interventions for the therapeutic management of pain in head and neck cancer patients with oral mucositis resulting from radiotherapy only or chemoradiotherapy. MATERIALS AND METHODS: A literature search was conducted which included randomised controlled trials that assessed patient-related outcome of pain in patients with oral mucositis associated with radiation therapy only or chemoradiotherapy. Literature searches were conducted in MEDLINE via Pubmed, Embase, Scopus and CINAHL. RESULTS: The electronic searches identified 846 articles. Screening revealed that six articles met all eligibility inclusion criteria. Interventions showing statistically significant benefits to reduce oral mucositis associated pain compared to placebo included doxepin (p < 0.001, 95% CI -6.7 to -2.1), amitriptyline (p = 0.04), diclofenac (p < 0.01) and benzydamine (p = 0.014). CONCLUSIONS: Non-opioid interventions, including topical doxepin, amitriptyline, diclofenac and benzydamine, were found to provide relief of pain due to mucositis, and when effective may allow for reduction in the use of opioids in pain management.

Selected highlights from clinical anesthesia and pain management.

STUDY OBJECTIVE: To review research highlights of manuscripts published in 2017 that pertain to all aspects of the clinical practice of anesthesiology. DESIGN: Narrative review. SETTING: N/A. MATERIALS: The major themes addressed in this review include recent studies examining airway management, obstetrical and gynecological anesthesia, pediatric anesthesia, cardiac anesthesia, regional analgesia and pain management. INTERVENTIONS: N/A. MAIN RESULTS: N/A. CONCLUSIONS: This review will highlight and inform anesthesiologists of the developing trends in clinical anesthesia and will also pose new challenges for further studies.