Risk Of Respiratory Depression Research Articles

Dexmedetomidine decreases stress post-operative in pediatrics

ABSTRACT Introduction Tracheal extubation causes hypertension and tachycardia. These associated hemodynamic changes are due to sympathetic discharge due to epipharyngeal and laryngeal stimulation.(1) Aim of work Dexmedetomidine is an effective sedative and analgesic agent, it helps in opioid sparing and multimodal techniques in pediatric anesthesia and reduces the toxicity of common anesthetics, and it has been approved by the end of 1999 by the FDA for human use for sedation in the intensive care unit (ICU). Dexmedetomidine is notable for its ability to provide sedation without risk of respiratory depression and can provide cooperative or arousable sedation. The aim of this study is to assess the effect of administering dexmedetomidine near the end of surgery versus a control group regarding the change in circulatory reflexes (represented by MAP) and the incidence of adverse events such as cough, laryngeal spasm or desaturation. Study design This study was designed as a prospective randomized controlled study. It was conducted in the Pediatrics orthopedic surgery theatre (Abo El Reesh pediatric Hospital) belonging to Cairo university hospitals on 70 patients divided into two groups 35 patients each and aged from 3–12 years planned for elective isolated limb anomaly correction. Result Dexmedetomidine injection near the end of the operation decreased the stress induced during extubation with almost no change in HR or MAP and less cough score, which indicated smoother extubation. Conclusion Dexmedetomidine is a potent alpha 2 receptor agonist, having analgesic and sedative effects and sparing usage of opioids without compromising respiratory reflexes or attenuating cardiovascular response during extubation.

Gabapentinoides en indicaciones no autorizadas en la ficha técnica: ¿es necesaria una estrategia de desprescripción?

ObjectiveTo evaluate gabapentin and pregabalin treatment adequacy to label indications, to analyze off-label use and to identify patients at high risk of respiratory depression. MethodAn observational, retrospective study was performed. It included patients treated with pregabalin and gabapentin during 2020 in Navarre. ResultsA total of 9778 patients were treated with gabapentin or pregabalin during the first two months of 2020. In 56% of the cases, gabapentinoids were prescribed for off-label uses. Sixty percent of patients were taking at least one central nervous system (CNS) depressant drug concomitantly, 33% of them opioids, 20% of them combined opioids with CNS depressants and 4% of them at least one systemic antihistamine. In addition, 11% of the patients had a diagnosis of asthma or COPD. Prevalences remained constant along the year. ConclusionsIt is necessary to implement a gabapentinoid deprescription strategy to improve its use and reduce safety problems.

Preparation and characterization of morphine gelatine microspheres

ABSTRACTMorphine is a widely used opioid analgesic. However, standard morphine dosages and administration methods exhibit a short half-life and pose a risk of respiratory depression. Sustained-release microspheres can deliver prolonged efficacy and reduce side effects. We present a new controlled-release morphine gelatine microsphere (MGM) prepared using an emulsification-crosslinking strategy. The gelatine microsphere design improves the bioavailability of morphine. And it not only increases the clinical analgesic efficacy but also the safety of clinical medication through a gradual, sustained release. Besides, we describe MGMs’ preparation, release, pharmacodynamics, and pharmacokinetics. And the drug metabolism pathway. We calculate the release rate of morphine by measuring plasma morphine concentration over time and pharmacokinetic parameters. It optimized the manufacturing process of MGMs, which makes the analgesic effect have a longer duration. MGMs analgesic effect shows dose dependence. After they were administrated, MGMs were released more slowly. Peak concentration was reduced, and the relative bioavailability improved. It even reached 88.84%. Its pharmacokinetic process was consistent with the two-component first-order absorption model. MGMs deliver sustained-release and long-action pharmacokinetics. It shows design goals of improving drug bioavailability, prolonging drug residence time in vivo, and maintaining stable blood drug concentration.

The efficacy and safety of remifentanil patient-controlled versus epidural analgesia in labor: A meta-analysis and systematic review.

Remifentanil patient-controlled analgesia (rPCA) and epidural analgesia (EA) has been used for pain relief in labor. We aimed to evaluate the efficacy and safety of rPCA versus EA in labor, to provide evidence support for clinical analgesia and pain care. We searched PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu databases for RCTs comparing rPCA and EA in labor until February 15, 2022. Two researchers independently screened literature and extracted data. RevMan 5.3 software was used for data analysis. A total of 10 RCTs involving 3086 parturients were enrolled, 1549 parturients received rPCA and 1537 received EA. Meta-analysis indicated that the incidence of intrapartum maternal fever within 1 hour of labor analgesia (OR = 0.43, 95%CI: 0.30~0.62), after 1 hour of labor analgesia (OR = 0.42, 95%CI: 0.20~0.90) in the rPCA was significantly less than that of EA (all P<0.05). The incidence of respiratory depression (OR = 3.56, 95%CI: 2.45~5.16, P<0.001) in the rPCA was significantly higher than that of EA. There were no significant differences in the incidence of Apgar scores<7 at 5 minutes (OR = 1.18, 95%CI: 0.71~1.96, P = 0.53), the patients' satisfaction of pain relief during labor analgesia (SMD = 0.03, 95%CI: -0.40~0.46, P = 0.90) between rPCA and EA (all P>0.05). rPCA can be an optional alternative to EA with similar pain relief and less risk of intrapartum maternal fever. However, rPCA was associated with increased risk of respiratory depression. Future studies with rigorous design and larger sample size are needed to provide more reliable evidences for clinical rPCA and EA use.

Gabapentinoids for Pain: A Review of Published Comparative Effectiveness Trials and Data Submitted to the FDA for Approval

Use of the gabapentinoids for pain continues to increase. In 2018, the US Food and Drug Administration (FDA) strengthened the warnings for both gabapentin and pregabalin to emphasize the central nervous system side effects and the risk of respiratory depression, especially when combined with other centrally acting drugs. We reviewed the published comparative effectiveness literature for gabapentinoids for pain as well as all trials (published and unpublished) used by the FDA for the approval of the five pain indications for these agents (one for gabapentin, four for pregabalin). Among the findings of interest are the fact that the FDA rejected the application for gabapentin for diabetic peripheral neuropathy based on the risk versus benefit profile of that drug in the clinical trials that were submitted by the manufacturer. Additionally, both the comparative effectiveness trials as well as the studies used by the FDA tend to be short in duration and show only modest pain benefits for the gabapentinoids. The placebo response in these trials was frequently one-third to one-half as great as the pain benefit demonstrated by the gabapentinoid. Based on the available clinical trial evidence, we feel prescribers should be cautious when using gabapentinoids for pain, particularly when using these agents for a prolonged period or when combined with other, centrally acting agents.

670 DEXMEDETOMIDINE SEDATION FOR PULMONARY VEIN ISOLATION PROCEDURE

Abstract Background Peri-procedural anesthesia for catheter ablation of atrial fibrillation (AF) varies from conscious sedation to general anesthesia. Current guidelines do not suggest any specific strategy, thus the choice between different protocols is mainly driven by local expertise, operator and/or patient preference and availability of a dedicated anesthesiology team. Propofol is often the drug of choice despite the risk of respiratory depression. Few data have recently reported operator-directed nurse-administered dexmedetomidine (DEX) sedation as an effective and safe strategy. Aim of the study To evaluate the outcomes of operator-directed nurse-administered DEX sedation in AF ablation (pulmonary vein isolation-PVI). Method Between May 2022 and August 2022, 41 consecutive patients (male 83%, median age 64 years, IQR 57-71) with drug-refractory paroxysmal (n.27;66%) or persistent AF (n.14;34%) underwent first PVI procedure under DEX sedation. Our sedation protocol consisted of continuous intravenous administration of DEX (0.2–0,7 µg/kg/hr) titrated throughout the procedure to achieve mild to moderate sedation (Modified Observer's Assessment of Alertness and Sedation Scale 2-3). A single dose of Ondansetron (4 mg) was administered in the beginning of procedure. Adjunctive doses of fentanyl (cumulative dose 50-100 µg) were administered before the beginning of radiofrequency (RF) delivery and in case of inadequate control of the pain. A low dose propofol bolus (&amp;lt;1mg/kg) was eventually added for electrical cardioversion (ECV). Sedation-related complications were evaluated, including sustained hypoxemia (SpO2 &amp;lt;90%), need of anesthesiologist support and persistent hypotension (SBP &amp;lt; 90 mmHg). The day after the procedure, patients’ satisfaction and pain (0-100 scale) were assessed by a standardized questionnaire. Results Pulmonary vein isolation was performed either with Low Power Long Duration (LPLD, n.17;41,46%) or High-Power Short Duration (HPSD, n.24;58,54%) RF protocol. Median procedure time was 135’ (IQR 110-170’). Median DEX dose was 0,30 µg/kg/hr (IQR 0,27-0,33 µg/kg/hr). Median fentanyl dose was 75 µg (IQR 50-100 µg). In patients needing for ECV (n. 16; 39%), median propofol dose was 60 mg (IQR 47,5–105 mg). Thirteen patients (31,7%) had one or more significant risk factor (obesity, severe heart failure, pulmonary comorbidity, coronary artery disease) for anesthesia-related complications. Median pain scale value was 20 (IQR 10-50). Majority of patients (90,2%, n.37) reported mild to moderate pain (pain &amp;lt;60/100) during the procedure and satisfaction was overall high (median value 90, IQR 80-100), with a 90,2% of patients declaring a satisfaction of 60/100 or more. These results were independent from baseline characteristics (sex, age, AF type, HF, CAD, pulmonary comorbidity, obesity) and procedural aspects (LPLD vs HPSD, procedure time, need for ECV). A strong linear correlation was found between patients’ satisfaction and reported pain (r=-0,59). Only 1 (2,4%) sedation-related complication occurred, consisting in sustained post procedural hypotension treated with volume repletion. Conclusions in our experience, dexmedetomidine (DEX) sedation protocol during catheter ablation of atrial fibrillation is associated to high patients’ satisfaction and no respiratory complications. It seems to be also feasible in patients at higher risk for anesthesia-related complications (severe heart failure, BMI &amp;gt; 30 kg/m2), generally excluded from previous studies.

Evaluation of concurrent benzodiazepine and opioid prescribing patterns with a focus on acute muscle spasms indication at hospital discharge

• Concurrent opioids and benzodiazepines increase risk of respiratory depression • Tools to promote risk mitigation with concurrent prescribing • Naloxone recommendations In 2016, the CDC Guidelines for Prescribing Opioids in Chronic Pain recommended avoiding the co-prescribing of opioids and benzodiazepines when possible. This evaluation provides one institution's approach to improve safety for new, acute concurrent opioid and benzodiazepine prescribing. Patients prescribed new, concurrent opioids and benzodiazepines upon discharge within one organization were identified. A chart review for the highest prescribing specialties was completed for a random sample of 100 patients to determine indications for prescribing, safety measures, and post discharge healthcare utilization. Orthopedic surgery, the hospitalist service, neurosurgery, and general surgery had the highest concurrent prescribing rates. The most common indication for benzodiazepine prescribing was muscle spasms, but quantity variability existed across and within all four specialties. Of the subset of patients reviewed, patients were consistently not prescribed naloxone. A prescribing guideline was implemented to provide educational tools, standardized benzodiazepine quantities, and naloxone co-prescribing recommendations for the indication of muscle spasms.

This Month in Anesthesiology

This Month in Anesthesiology

Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia

Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects. To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia. Randomized, double-blind, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) with 25 healthy participants from January 2021 through May 25, 2021. Oxycodone 10 mg on days 1 and 5 and the following in a randomized order for 5 days: paroxetine 40 mg daily, quetiapine twice daily (increasing daily doses from 100 mg to 400 mg), or placebo. Ventilation at end-tidal carbon dioxide of 55 mm Hg (hypercapnic ventilation) using rebreathing methodology assessed for paroxetine or quetiapine with oxycodone, compared with placebo and oxycodone, on days 1 and 5 (primary) and for paroxetine or quetiapine alone compared with placebo on day 4 (secondary). Among 25 participants (median age, 35 years [IQR, 30-40 years]; 11 female [44%]), 19 (76%) completed the trial. The mean hypercapnic ventilation was significantly decreased with paroxetine plus oxycodone vs placebo plus oxycodone on day 1 (29.2 vs 34.1 L/min; mean difference [MD], -4.9 L/min [1-sided 97.5% CI, -∞ to -0.6]; P = .01) and day 5 (25.1 vs 35.3 L/min; MD, -10.2 L/min [1-sided 97.5% CI, -∞ to -6.3]; P < .001) but was not significantly decreased with quetiapine plus oxycodone vs placebo plus oxycodone on day 1 (33.0 vs 34.1 L/min; MD, -1.2 L/min [1-sided 97.5% CI, -∞ to 2.8]; P = .28) or on day 5 (34.7 vs 35.3 L/min; MD, -0.6 L/min [1-sided 97.5% CI, -∞ to 3.2]; P = .37). As a secondary outcome, mean hypercapnic ventilation was significantly decreased on day 4 with paroxetine alone vs placebo (32.4 vs 41.7 L/min; MD, -9.3 L/min [1-sided 97.5% CI, -∞ to -3.9]; P < .001), but not with quetiapine alone vs placebo (42.8 vs 41.7 L/min; MD, 1.1 L/min [1-sided 97.5% CI, -∞ to 6.4]; P = .67). No drug-related serious adverse events were reported. In this preliminary study involving healthy participants, paroxetine combined with oxycodone, compared with oxycodone alone, significantly decreased the ventilatory response to hypercapnia on days 1 and 5, whereas quetiapine combined with oxycodone did not cause such an effect. Additional investigation is needed to characterize the effects after longer-term treatment and to determine the clinical relevance of these findings. ClinicalTrials.gov Identifier: NCT04310579.

Quality of recovery after intrathecal morphine for elective Caesarean deliveries

Background: Recent supply issues with diamorphine have meant a change in practice to use of intrathecal morphine. The Obstetric Anaesthetists’ Association (OAA)1 guidelines state that intrathecal diamorphine or morphine provides adequate analgesia after Caesarean section. They discourage the use of parenteral opioids in women who have received neuraxial opioids, owing to the increased risk of respiratory depression. Other side-effects such as nausea and vomiting and pruritus may differ in severity for each drug. We reviewed the side-effects and adherence to the enhanced recovery pathway in elective deliveries receiving intrathecal morphine. Methods: Prospective data were collected for 50 women undergoing Caesarean section with intrathecal opioid analgesia (fentanyl 15 μg and morphine 100 μg) within a 5-week period. Data were collected at Day 1 and Day 2 postoperatively. These included: pain score, postoperative nausea and vomiting (PONV), pruritus, oral opioid use, anti-emetic use, chlorphenamine use, time spent in recovery, and occurrence of urinary retention. Pain score, nausea and vomiting, and pruritus were recorded using a verbal rating scale (VRS). Results: The majority (56.5%) of patients reported only mild pain, 37% reported moderate to severe pain, but of these most (94.7%) only required 20–40 mg of oral morphine in addition to simple analgesia. In addition, the majority (58.7%) of patients reported no PONV. Meanwhile, 45.7% of patients reported mild pruritus, and 43.5% reported no pruritus. Only three of the 50 women did not follow the enhanced recovery pathway. Two remained as inpatients for monitoring after obstetric haemorrhage, and one for intravenous antibiotics. There was no reported respiratory depression. Time spent in recovery was between 1 and 4 h. Although the reason for prolonged recovery stay was not audited, it was thought that requirement for oxytocin infusion increased recovery stay as the ward did not accept patients on an infusion. Conclusions: Our results show an acceptable side-effect profile after elective Caesarean delivery using intrathecal morphine, with adherence to the current enhanced recovery pathway. We aim to implement updated Caesarean delivery guidelines which include prescription of regular ondansetron and chlorphenamine as required, in conjunction with patient education, to try and reduce the incidence of bothersome PONV and pruritus. 1. Obstetric Anaesthetists’ Association, OAA commentary on alternatives to intrathecal and epidural diamorphine for caesarean section analgesia, 2018. Available from: https://www.oaa-anaes.ac.uk/ui/content/content.aspx?ID=4717

The comparison of ketamine-dexmedetomidine (ketadex) and ketamine-propofol (ketofol) for procedural sedation in pediatric patients: A meta-analysis of randomized controlled trials

IntroductionThe combination of different agents used for procedural sedation allows a greater range of desirable effects while minimizing side effects. The ketamine-dexmedetomidine combination (ketadex) and ketamine-propofol combination (ketofol) are successful examples. The purpose of this meta-analysis was to compare the safety and efficacy of ketadex with ketofol used for procedural sedation in pediatric patients. MethodsWe searched Pubmed, Cochrane Controlled Register of Trials, and Embase from inception to June 2022. Studies were independently evaluated for inclusion criteria and exclusion criteria by two reviewers. Outcome measures for safety comparison were the incidence of hypotension, bradycardia, respiratory depression, nausea, vomiting, and agitation; Outcome measure for efficacy comparison was clinicians' satisfaction. In addition, we compared the recovery time of ketadex and ketofol. ResultsNine studies were included in this meta-analysis. Compared with ketofol, ketadex sedation in pediatric patients had lower risk of respiratory depression (RR: 0.51, 95% CI: 0.34–0.76, P = 0.0009). However, ketadex displayed significant effect on recovery time (MD: 8.38 min, 95% CI: 7.55–9.22 min, P < 0.00001). Ketadex had similar incidence of hypotension (RR: 0.95, 95% CI: 0.33–2.67, P = 0.92) and bradycardia (RR: 1.80, 95% CI: 0.64–5.06, P = 0.26) compared to those with ketofol. Clinicians' satisfaction rate of ketadex and ketofol were both high (RR: 0.93, 95% CI: 0.69–1.25, P = 0.62). Also, no significant difference was observed between ketadex and ketofol on the incidence of nausea, vomiting, and agitation. ConclusionsBoth ketadex and ketofol can provide effective sedation and maintain stable hemodynamics. In consideration of good safety profile in respiratory problems, we suggest ketadex is a better option for procedural sedation in pediatric patients.

A single-sided trans-nasal catheter for smooth and efficient oxygen delivery can improve the safety in patients undergoing pancreato-biliary endoscopy under intravenous sedation: A randomized trial.

BackgroundPancreato‐biliary endoscopic procedures often need to be performed under deep intravenous sedation. The patients are at an increased risk of respiratory depression influenced by the anatomical dead space of the upper respiratory system. We aimed to evaluate the benefit of oxygen delivery through a single‐sided trans‐nasal catheter (TC) for patients undergoing pancreato‐biliary endoscopy.MethodsOxygen supplementation during the procedure was provided either by insertion of a single‐sided TC or insertion of a conventional nasal catheter (NC). A prospective, single‐blind, randomized controlled study was conducted in two groups.ResultsThe number of patients who indicated a decrease in the peripheral transcutaneous oxygen saturation (SpO2; desaturation) was significantly lower in the TC group than in the counterpart (8/58; 13.8% vs. 26/58; 44.8% p < 0.001). The efficient oxygen delivery in the safe range was better conserved in the TC group than in the NC one. There was no adverse effect on both groups. The maximum SpO2 while the endoscopic procedure was significantly higher in the TC group (99.7% vs. 99.3% p = 0.016) and the minimum SpO2 was also significantly higher in the same group (97.7% vs. 94.1% p < 0.0001), which meant that the efficient oxygen delivery was better maintained in TC group than the NC group.ConclusionsA single‐sided TC placed in the pharynx in patients undergoing pancreato‐biliary endoscopy prepares a superior condition of the patients for venous sedation, maintained hyper‐oxygen saturation and a relatively higher SpO2 level to be maintained in limited conditions to reduce the dead space with acceptable tolerance, as compared to the placement of a conventional NC.

Rapid Tranquilisation Use in Working-Age Adult Inpatients

AimsThis study aimed to review if clinicians varied significantly in choosing rapid tranquillisation agents when using consistent clinical guidelines, analysing the rationale behind decision-making. It also aimed to assess confidence across varying grades and clinical experience, and to evaluate efficacy of current trust guidelines. We hypothesized that less experienced clinicians would be less willing to prescribe antipsychotics for rapid tranquillisation, and that current guidelines did not allow for consistent and uniform prescribing.MethodsA qualitative survey was distributed to 165 clinicians within one mental health trust, including core psychiatry trainees, trust-grade doctors, higher trainees, staff-grade doctors &amp; working-age adult consultants. This survey included a fictional but commonly occurring scenario which clinicians responded to with the aid of current trust guidance. Respondents were then asked to justify their choice and to rank their confidence in prescribing rapid tranquillisation, along with rating how useful the guideline was in aiding their decision. Thirty-six participants responded to this survey, with a response rate of around 22%. There was even representation across clinical grades.ResultsClinicians of all grades were equally willing to prescribe antipsychotic agents for rapid tranquillisation. Higher psychiatric trainees reported greatest self-confidence when prescribing tranquillisation, with consultants surprisingly lower in confidence. Intramuscular olanzapine was most favourable, but significant variability was observed in suggested management between clinicians. Main themes for suggested amendments to the guideline included clarity, when to use the various options, further specification on dosage ranges and options for specific instances, such as if a patient is antipsychotic naïve or there is minimal physical health information.There was marked variability in choice of agent. The majority of clinicians felt that early commencement of antipsychotic was beneficial in acutely unwell patients, although the merits of initially assessing medication-free were also raised. Key themes for tranquillisation choice included a need for a prior electrocardiogram to prescribe intramuscular haloperidol, the potential lack of efficacy with aripiprazole, the risk of respiratory depression with concurrent olanzapine and lorazepam, and a surprisingly high proportion of respondents opting for combined use of haloperidol plus a further sedative.ConclusionLess experienced clinicians were not found to lack confidence to prescribe antipsychotics for rapid tranquillisation. However, clinicians responding to the same clinical scenario using the same guideline resulted in marked variability in choosing rapid tranquillisation agents. This highlights a need for clearer guidelines and education on this matter to ensure a consistent treatment approach to tranquillising medication.

ID:15929 Secondary Respiratory Outcomes of a Phase 1 Placebo-Controlled Trial: Buprenorphine Buccal Film Versus Oral Oxycodone

Buprenorphine is a Schedule III opioid with partial mu-opioid receptor agonist activity.1 The unique receptor activity profile of buprenorphine induces effective analgesia and decreases the risk of respiratory depression when compared with Schedule II full-mu opioid receptor agonists.1,2 This phase 1 study (ClinicalTrials.gov, NCT03996694) was conducted to directly compare the effect of buprenorphine buccal film (BioDelivery Sciences International, Inc.) with that of a full mu-opioid receptor agonist, oxycodone hydrochloride (immediate-release), on respiratory drive.3 The primary outcome of this study was the maximum decrease in minute ventilation; buprenorphine buccal film did not suppress respiratory drive compared with placebo, whereas oxycodone showed a significant dose-dependent decrease in respiratory drive. Additional clinically relevant outcomes were assessed throughout the study and are presented here.

WEBB FELLOW: Respiratory Depression Risk with Co-administered Parenteral Olanzapine and Benzodiazepines: A Retrospective Study

WEBB FELLOW: Respiratory Depression Risk with Co-administered Parenteral Olanzapine and Benzodiazepines: A Retrospective Study

Intrathecal Fentanyl With a Myofascial Plane Block in Open Lumbar Surgeries: A Case Series.

Acute postoperative pain control after lumbar surgery is imperative to minimizing long-term narcotic use and associated adverse sequela. The safety of intrathecal morphine for postoperative pain management in spine surgery has been investigated; however, to date, no studies have investigated the safety of intrathecal fentanyl with a myofascial plane (MP) block in lumbar procedures. To assess the safety profile of intrathecal fentanyl with a MP block administered during lumbar surgery and the subsequent utilization of postoperative intravenous opioids. An intraoperative intrathecal injection of fentanyl and a MP block was administered in 40 patients undergoing open lumbar reconstructive surgery. The procedure performed was an open decompression with lumbar total joint reconstruction at 1 to 3 lumbar levels. Postoperative complications including urinary retention, respiratory depression, and need for IV opioid use were recorded. Postoperatively, none of the study patients required IV opioid medication for supplemental pain control. Thirty-six patients (85%) were discharged same day or before 23 hours postoperatively. No intrathecal fentanyl-related perioperative complications were noted. None of the 40 listed patients experienced urinary retention or delayed respiratory depression. One patient (2%) experienced orthostatic hypotension at postoperative day 1, which resolved on discontinuation of oral oxycodone. Intrathecal fentanyl and MP block may be a safe option for perioperative pain control and may reduce the need for supplemental intravenous opioids without increased risk of respiratory depression, urinary retention, or other side effects. Further studies are necessary to compare the efficacy of intrathecal fentanyl with other analgesia techniques.

Risk Stratification of Respiratory Depression with Buprenorphine Buccal Film Versus Oxycodone: Phase 1 Trial Outcomes

INTRODUCTION: A phase 1 study (ClinicalTrials.gov, NCT03996694) assessed the effects of buprenorphine buccal film (BBF) and oxycodone on respiratory drive. The risk of respiratory depression was established for BBF and oxycodone using a new risk classification method. Methods: This randomized, double-blind, double-dummy, 6-treatment, 6-period, placebo-controlled crossover study evaluated respiratory drive in healthy, self-identified recreational opioid users via the ventilatory response to hypercapnia by maximum decrease in minute ventilation (primary endpoint) after the administration of BBF (300, 600, and 900 µg), immediate-release oral oxycodone (30 and 60 mg), and placebo.

Postoperative Respiratory Events in Surgical Patients Exposed to Opioid Analgesic Shortages Compared to Fully Matched Patients Non-exposed to Shortages.

Shortages of opioid analgesics critically disrupt clinical practice and are detrimental to patient safety. There is a dearth of studies assessing the safety implications of drug shortages. We aimed to assess perioperative opioid analgesic use and related postoperative hypoxemia (oxygen saturation less than 90%) in surgical patients exposed to prescription opioid shortages compared to propensity score-matched patients non-exposed to opioid shortages. We conducted a retrospective study including adult patients who underwent elective surgery at The University of California San Francisco in the period August 2018-December 2019. We conducted a Gamma log-link generalized linear model to assess the effect of shortages on perioperative use of opioids and a weighted logistic regression to assess the likelihood of experiencing postoperative hypoxemia. There were 1119 patients exposed to opioid shortages and 2787 matched non-exposed patients. After full matching, patients exposed to shortages used a greater mean of morphine milligram equivalents/day (146.94; 95% confidence interval 123.96-174.16) than non-exposed patients (117.92; 95% confidence interval 100.48-138.38; p=0.0001). The estimated effect was a 1.25 (95% confidence interval 1.12-1.40; p=0.0001) times greater use of opioids in patients exposed to opioid shortages than non-exposed patients. After full matching, a greater proportion of patients exposed to shortages (19.06%) experienced hypoxemia compared with non-exposed patients (16.91%). In addition, a greater proportion of patients exposed to opioid shortages (1.20%) experienced hypoxemia reversed by intravenous naloxone administration compared with non-exposed patients (0.44%). Given the shortage prevalence, reliance on opioid medications, and related risk of respiratory depression, harm prevention measures remain critical to prevent postoperative complications that may compromise patients' safety.

Undetected Respiratory Depression in People with Opioid Use Disorder

BackgroundOpioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respiratory depression (RD) in OUD treatment and compared this to patients with chronic obstructive pulmonary disease (COPD) of equivalent severity. We also explored the contribution of opioid agonist treatment (OAT) dosage, and type, to the prevalence of RD. MethodsThere were four groups of participants: 1) OUD plus COPD (‘OUD-COPD’, n = 13); 2) OUD without COPD (‘OUD’, n = 7); 3) opioid-naïve COPD patients (‘COPD’n = 13); 4) healthy controls (‘HC’n = 7). Physiological indices, including pulse oximetry (SpO2%), end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and second intercostal space parasternal muscle electromyography (EMGpara), were recorded continuously over 40 min whilst awake at rest. Significant RD was defined as: SpO2%< 90% for > 10 s, ETCO2 per breath > 6.6 kPa, TcCO2 overall mean > 6 kPa, respiratory pauses > 10 s ResultsAt least one indicator was observed in every participant with OUD (n = 20). This compared to RD episode occurrence in only 2/7 HC and 2/13 COPD participants (p < 0.05,Fisher’s exact test). The occurrence of RD was similar in OUD participants prescribed methadone (n = 6) compared to those prescribed buprenorphine (n = 12). ConclusionsUndetected RD is common in OUD cohorts receiving OAT and is significantly more severe than in opioid-naïve controls. RD can be assessed using simple objective measures. Further studies are required to determine the association between RD and overdose risk.

443 Intrathecal Fentanyl With a Myofascial Plane Block in Open Lumbar Surgeries

INTRODUCTION: Acute postoperative pain control following lumbar surgery is imperative to minimizing long term narcotic use and associated adverse sequela. The utility and safety of intrathecal morphine for postoperative pain management in spine surgery has been investigated; however, to date, no studies have investigated the safety of intrathecal fentanyl with a myofascial plane block in lumbar procedures. METHODS: An intraoperative intrathecal injection of fentanyl and a myofascial plane block was administered in 40 patients undergoing open lumbar surgery. The procedure performed was an open decompression with lumbar total joint reconstruction at one to three lumbar levels. Postoperative complications including urinary retention, respiratory depression, and need for IV opioid use were recorded. RESULTS: Postoperatively, zero of the study patients required IV opioid medication for supplemental pain control. Thirty-six patients (85%) were discharged same-day or prior to 23 hours postoperatively. No intrathecal fentanyl-related perioperative complications were noted. Zero of the 40 listed patients experienced urinary retention or delayed respiratory depression. One patient (2%) experienced orthostatic hypotension postoperative day one, which resolved upon discontinuation of oral oxycodone. CONCLUSION: Intrathecal fentanyl and myofascial plane block may be a safe option for perioperative pain control and may reduce the need for supplemental intravenous opioids without increased risk of respiratory depression, urinary retention, or other sequelae. Further studies are necessary to compare the efficacy of intrathecal fentanyl to other analgesia techniques.