Severe Respiratory Depression Research Articles

Bioabsorbable, subcutaneous naltrexone implants mitigate fentanyl-induced respiratory depression at 3 months-A pilot study in male canines.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 μg/kg and especially at 120 μg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

A Case Report of Delayed Opioid Toxidrome After Administration of Naloxone.

Opioid use is an epidemic that plagues the United States. Patients frequently present to the emergency department (ED) after opioid toxicity, which can lead to respiratory failure, apnea, and death. Although there is an effective antidote, naloxone, the current guidelines surrounding post-naloxone administration monitoring are loosely defined. We present a case in which an individual was administered naloxone after an intentional opioid overdose and was monitored for four hours, as is standard in our institution. He remained in the ED for additional workup following this observation period and subsequently experienced signs of severe respiratory depression, requiring bag-valve-mask ventilation, naloxone, and admission. Had he been discharged, as is typical after a four-hour observation period, the consequences could have been fatal. We present multiple theories as to why his opioid toxidrome may have presented in a delayed manner, including ingestion of fentanyl analogues and variability in metabolization of both opioids and naloxone. We also explore alternative overdose antidote products approved by the US Food and Drug Administration, which may impact post overdose care. This case suggests that the correct amount of time to monitor patients after naloxone administration may be longer than originally thought. Our aim in this article was to further the discussion regarding the most appropriate observation period in cases of opioid toxicity.

Half a Decade of Intravenous Ketamine Administration: Our Observation Results and Insights regarding its safety

IntroductionKetamine, originally an anesthetic, has emerged as a potent tool in the fight against treatment-resistant depression and suicide. Clinical trials have demonstrated its ability to induce remission of severe depressive symptoms, with effects that can extend over several weeks.Furthermore, research highlights Ketamine’s potential to rapidly reduce suicidal ideation. This suggests Ketamine’s role as an intervention in suicide prevention, especially when conventional treatments prove ineffective. While isolated cases report severe respiratory depression, primarily when combined with other medications, most incidents involve temporary apneic episodes following high-dose intravenous administration. Understanding Ketamine’s safety profile is vital for its clinical optimization and ensuring patient well-being during useObjectivesThis presentation serves to describe, and evaluate our clinic’s safety protocol implemented for intravenous (IV) Ketamine infusions at the General Hospital of Corfu. Our primary goal is to rigorously assess the safety and tolerability of IV Ketamine in a clinical settingMethodsPatients must meet stringent criteria:-Exclude those over 70.-MMSE score above 25.-Controlled blood pressure.-No cardiac insufficiency, myocardial ischemia, or high intraocular/intracranial pressure.-Absence of thyrotoxicosis, psychosis, or seizures.Pre-infusion comprehensive evaluation:-Includes ECG, blood biochemistry studies, and frequent blood pressure checks.-Requires a 2-hour fast.Ketamine infusion:-IV Ketamine administered at 0.5mg/kg in 100ml N/S.-Continuous monitoring of oxygen saturation (PO2) and cardiac rhythm.-Blood pressure checks every 15 minutes.Treatment typically involves 7 sessions over a span of a month, with an initial test dose of 0.25 mg/kg.ResultsKetamine infusions were administered to a total of 208 patients. The majority of participants experienced a slight increase in blood pressure, while there were no significant changes in cardiac rhythm. Additionally, almost all patients reported experiencing dizziness or headaches during the infusion. Notably, nearly half of the patients reported an alteration in taste perception as a side effect. It’s important to highlight that all observed side effects, spontaneously resolved within an hour after the conclusion of the infusion. However, in a small subset of cases (six instances), the side effects were severe enough to necessitate the premature termination of the ketamine infusionConclusions Although ketamine demonstrates a favorable safety profile with minimal major side effects when administered following our established safety protocol. However, we want to underscore the critical importance of vigilant patient monitoring during ketamine administration and the prompt addressing of any adverse effects. This proactive approach is paramount to ensure the safety and overall well-being of patients receiving ketamine treatmentDisclosure of InterestNone Declared

Newcastle Disease - overview and analysis of the current spread of the disease in Bulgaria and Europe

Newcastle disease (ND) is a highly contagious and severe worldwide disease affecting birds. The infection is a mild zoonosis and can cause conjunctivitis in humans, but the condition is usually mild and self-limiting. ND is caused by virulent strains of avian paramyxovirus type 1. The disease occurs in five forms: velogenic viscerotrophic, velogenic neutrotropic, mesogenic, lentogenic Newcastle disease and asymptomatic enteric Newcastle disease. Lentogenic strains are very widespread, but are usually asymptomatic and do not cause outbreaks in poultry. Newcastle disease in its highly pathogenic form, is a WOAH listed disease and must be reported. It usually manifests as severe respiratory disease, depression, nervousness and/or diarrhea. The clinical picture is very similar to bird flu, so laboratory tests are important to confirm the diagnosis.

Analysis of the efficacy of subclinical doses of esketamine in combination with propofol in non-intubated general anesthesia procedures - a systematic review and meta-analysis

BackgroundThe number of non-intubated general anesthesia outside the operating room is growing as the increasing demand for comfort treatment. Non-intubated general anesthesia outside the operating room requires rapid onset of anesthesia, smoothness, quick recovery, and few postoperative complications. Traditional anesthetic regimens (propofol alone or propofol and opioids/dezocine/midazolam, etc.) have severe respiratory and circulatory depression and many systemic adverse effects. In this paper, we compare the effectiveness and safety of propofol and subclinical doses of esketamine with other traditional regimens applied to non-intubated general anesthesia through a systematic review and meta-analysis.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Sinomed databases for the period from January 2000 to October 2022. We rigorously screened the literature according to predefined inclusion and exclusion criteria, while risk assessment of the studies was performed using The Cochrane Collaboration’s tool, and statistical analysis of the data was performed using RevMan 5.4 software. The main outcome indicators we evaluated were the various hemodynamic parameters and incidence of various adverse effects between the experimental and control groups after induction of anesthesia.ResultsAfter a rigorous screening process, a total of 14 papers were included in the final meta-analysis. After risk bias assessment, three of the papers were judged as low risk and the others were judged as having moderate to high risk. Forest plots were drawn for a total of 16 indicators. Meta-analysis showed statistically significant differences in HR’ WMD 3.27 (0.66, 5.87), MAP’ WMD 9.68 (6.13, 13.24), SBP’ WMD 5.42 (2.11, 8.73), DBP’ WMD 4.02 (1.15, 6.88), propofol dose’ SMD -1.39 (-2.45, -0.33), hypotension’ RR 0.30 (0.20, 0.45), bradycardia’ RR 0.33 (0.14, 0.77), hypoxemia or apnea’ RR 0.45 (0.23, 0.89), injection pain’ RR 0.28 (0.13, 0.60), intraoperative choking’ RR 0.62 (0.50, 0.77), intraoperative body movements’ RR 0.48 (0.29, 0.81) and overall incidence of adverse reactions’ RR 0.52 (0.39, 0.70).The indicators that were not statistically different were time to wake up’ WMD − 0.55 (-1.29, 0.19), nausea and vomiting 0.84’ RR (0.43, 1.67), headache and dizziness’ RR 1.57 (0.98, 2.50) and neuropsychiatric reaction’ RR 1.05 (0.28, 3.93). The funnel plot showed that the vast majority of studies fell within the funnel interval, but the symmetry was relatively poor.ConclusionIn non-intubated general anesthesia, the combination of subclinical doses of esketamine and propofol did reduce circulatory and respiratory depression, injection pain, and other adverse effects, while the incidence of esketamine’s own side effects such as neuropsychiatric reactions did not increase, and the combination of the two did not cause the occurrence of new and more serious adverse reactions, and the combination of the two was safe and effective.Trial registrationPROSPREO registration number: CRD 42022368966.

Neurogenetics: Congenital Myotonic Dystrophy with asymptomatic mother may be missed by whole exome sequencing; Biopsy, DMPK1 gene testing and EMG may be required to resolve VUS in neonates, A Case report. (P6-8.010)

<h3>Objective:</h3> We show how biopsy, EMG, and <i>DMPK1</i> gene testing may be required for variant resolution. Whole exome sequencing revealed <i>NEB</i> (nebulin) (OMIM #161650) variants of uncertain significance inherited in <i>trans</i>. Muscle biopsy and EMG were helpful in resolving <i>NEB</i> VUS (variants of uncertain significance) and the detection of myotonia even as young as 6 days of age, with a clinically asymptomatic mother. <h3>Background:</h3> Myotonic dystrophy type 1 (myotonia dystrophia 1) is an autosomal dominant multisystem disorder caused by CTG expansion of the <i>DMPK1</i> gene (dystrophia myotonica protein kinase) (OMIM #605377) resulting in anticipation, whereby offspring have greater repeat expansion and severity. <h3>Design/Methods:</h3> <h3>Case Report:</h3> This full-term patient was born with severe hypotonia and respiratory depression. Brain MRI, EEG, Karyotype (46, XY) and FISH were normal. Whole Exome Sequencing (WES) revealed heterozygous <i>NEB</i> VUS, in <i>trans</i>, but histochemical and electron microscopic examinations of the muscle biopsy did not show nemaline rods. EMG was performed and revealed myotonic discharges. A genetic diagnosis of myotonic dystrophy type 1 was made, with over 200 CTG repeats in the <i>DMPK1</i> gene. A week after tracheostomy and g-tube placement, oxcarbazepine was trialed, after which he was able to be weaned off ventilation and discharged to home. He made substantial progress over the next year. <h3>Results:</h3> NA <h3>Conclusions:</h3> Neonatal muscle biopsies may not show nemaline rods due to being early or sampling error and thus further testing may be required. When evaluating severe congenital myopathies, testing for myotonic dystrophy should be considered. Myotonia may be found in neonates as young as 6 days old characterized as briefer duration with waning repetitive small amplitudes between 50–100uV without the classic sound on a spectrum with complex repetitive discharges. Severe congenital myotonic dystrophy patients may be born from an asymptomatic mother and the diagnosis may be missed by whole exome sequencing. <b>Disclosure:</b> Mr. Appiah has nothing to disclose. Dr. Shergelashvili has nothing to disclose. Dr. Marr has nothing to disclose. Ahmed Eldokla has nothing to disclose. Dr. LEBEL has nothing to disclose. Dr. Sakonju has nothing to disclose.

Severe Respiratory Depression in a Beta-Thalassemia Patient: A Case of Furosemide-Induced Hypokalemia Precipitated by Morphine

ABSTRACT This case report describes a rare occurrence of severe respiratory failure in a 4-year-old child with beta-thalassemia after the administration of Furosemide and morphine. The patient experienced hypokalemia (potassium levels - 2.69 mmol/L) following Furosemide administration, which worsened after morphine intake, leading to Type II respiratory failure. Immediate potassium correction and naloxone administration were initiated, but unfortunately, the patient succumbed to complications related to tracheostomy on D + 39. This report emphasizes the potential risks of Furosemide-induced hypokalemia and its interaction with morphine, resulting in severe respiratory depression.

Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The combination between medetomidine, midazolam, and butorphanol (MMB) is commonly used in different animal models. The possibility of MMB combination to establish the MI model in rats did not study yet which is difficult because of severe respiratory depression and delayed recovery post-surgery, resulting in significant deaths. Atipamezole is used to counter the cardiopulmonary suppressive effect of MMB. The aim of the present study is to establish MI model in rats using a novel anesthetic combination between MMB and Atipamezole. Twenty-five Sprague Dawley (SD) rats were included. Rats were prepared for induction of the Myocardial infarction (MI) model through thoracotomy. Anesthesia was initially induced with a mixture of MMB (0.3/5.0/5.0 mg/kg/SC), respectively. After endotracheal intubation, rats were maintained with isoflurane 1% which gradually reduced after chest closing. MI was induced through the left anterior descending (LAD) artery ligation technique. Atipamezole was administered after finishing all surgical procedures at a dose rate of 1.0 mg/kg/SC. Cardiac function parameters were evaluated using ECG (before and after atipamezole administration) and transthoracic echocardiography (before and 1 month after MI induction) to confirm the successful model. The induction time, operation time, and recovery time were calculated. The success rate of the MI model was also calculated. MI was successfully established with the mentioned anesthetic protocol through the LAD ligation technique and confirmed through changes in ECG and echocardiographic parameters after MI. ECG data was improved after atipamezole administration through a significant increase in heart rate (HR), PR Interval, QRS Interval, and QT correction (QTc) and a significant reduction in RR Interval. Atipamezole enables rats to recover voluntary respiratory movement (VRM), wakefulness, movement, and posture within a very short time after administration. Echocardiographic ally, MI rats showed a significant decrease in the left ventricular wall thickness, EF, FS, and increased left ventricular diastolic and systolic internal diameter. In addition, induction time (3.440 ± 1.044), operation time (29.40 ± 3.663), partial recovery time (10.84 ± 3.313), and complete recovery time (12.36 ± 4.847) were relatively short. Moreover, the success rate of the anesthetic protocol was 100%, and all rats were maintained for 1 month after surgery with a survival rate of 88%. Our protocol produced a more easy anesthetic effect and time-saving procedures with a highly successful rate in MI rats. Subcutaneous injection of Atipamezole efficiently counters the cardiopulmonary side effect of MMB which is necessary for rapid recovery and subsequently enhancing the survival rate during the creation of the MI model in rats.

Structure-based drug discovery facilitates future painkiller development.

Structure-based drug discovery facilitates future painkiller development.

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.

323 Phenobarbital Protocol for Alcohol Withdrawal Syndrome Reduces ICU Length of Stay in Trauma and Burn Patients

323 Phenobarbital Protocol for Alcohol Withdrawal Syndrome Reduces ICU Length of Stay in Trauma and Burn Patients

PC-FACS FINAL June 3, 2022

Background: Opioid analgesics, widely used to treat acute, postoperative, and chronic pain, can result in severe respiratory depression.1–3 Can tandospirone, a novel nonbenzodiazepine anxiolytic/antidepressant drug and selective serotonin-1A receptor partial agonist, counter fentanyl-induced respiratory depression?

Effects of dezocine combined with dexmedetomidine on adverse reactions and inflammatory factors in patients undergoing HIPEC after intestinal surgery and its protective effect on the heart in the perioperative period.

The aim of this study was to explore the effects of dezocine combined with dexmedetomidine on adverse reactions and inflammatory factors in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) after intestinal surgery and its protective effect on the heart in the perioperative period. A total of 80 patients treated with HIPEC after intestinal surgery in our hospital from September 2018 to December 2019 were enrolled as research subjects. All patients were evenly divided into two groups using a random number table. As to analgesia and sedation during treatment, dezocine was injected intramuscularly at 30 min before treatment in the control group. Meanwhile, dezocine combined with dexmedetomidine was given in the same way in the observation group. Adverse reactions and changes in numeric rating scale (NRS) pain score during intervention were compared between the two groups. The changes in the levels of inflammatory and myocardial injury-related factors, and vascular endothelial function and regeneration ability among cardiovascular indicators at 12 h after intervention were compared as well. Additionally, the correlations of left ventricular mass index (LVMI) with the changes in the levels of inflammatory factor high-sensitivity C-reactive protein (hs-CRP), myocardial injury-related factor lactic dehydrogenase (LDH), vascular endothelial function indicator endothelin-1 (ET-1) and cardiovascular regeneration ability index vascular endothelial growth factor (VEGF) were analyzed. Compared with control group, the total prevalence rate of severe pain, respiratory depression, nausea and vomiting, diarrhea, and muscle rigidity during intervention was significantly reduced in the observation group (p<0.05). NRS pain score at 1, 4, 8 and 12 h after intervention decreased remarkably in the observation group compared with the control group (p<0.05). Meanwhile, the levels of inflammatory factors tumor necrosis factor-α (TNF-α) and hs-CRP, and myocardial injury-related factors LDH and creatine kinase MB (CKMB) as well as ET-1 at 12 h after intervention declined remarkably in observation group compared with control group (p<0.05). However, the levels of nitric oxide (NO), VEGF and basic fibroblast growth factor (bFGF) rose significantly in the observation group (p<0.05). Besides, LVMI was positively correlated with hs-CRP and LDH, whereas was negatively associated with ET-1 and VEGF (p<0.05). In HIPEC, dezocine combined with dexmedetomidine used for sedation and analgesia is able to effectively reduce adverse reactions and relieve inflammatory responses in vivo, exerting a cardio-protective effect.

A Non‐Human Primate Model of Carfentanil Overdose: Preventing Renarcotization with Superior Countermeasures

We established a physiological and overt intoxication model using African green monkeys (Chlorocebus aethiops sabeus) and a high dose of injected carfentanil. Intoxication is rapid and rescue is typically required within 10 minutes. Naloxone, administered at a 10 mg human‐equivalent dose (HED; 0.355 mg/kg), is immediately effective but is limited by its short duration of action. Specifically, animals typically return to a state of severe respiratory depression within about 2.5 hours, necessitating further medical intervention. Therefore, we studied two novel medical countermeasures: nalmefene and CS‐1131. Nalmefene is a mu‐opioid antagonist with high affinity and a much longer duration of action, but little is known about its efficacy against carfentanil. Therefore, we covered a range of doses from 3‐30 mg estimated HED (based upon allometric scaling) through both the intramuscular and intranasal routes. CS‐1131 is a novel opioid scavenger (created by Clear Scientific, LLC) capable of binding carfentanil stoichiometrically, inactivating the synthetic opioid, and then eliminating the scavenger‐opioid complex through renal excretion. Results show that both countermeasures were superior to naloxone alone and exhibited dose‐dependent efficacy. This research provides strong proof‐of‐concept and sets the stage for additional studies of longer‐lasting opioid antagonists administered through various routes, and for the further development, characterization, and refinement of novel opioid scavenger molecules. This non‐human primate model can be utilized to study potent synthetic opioids, new analogues, and other novel countermeasures in a way that yields predictive results to support human clinical trials.

Comparison of low-dose morphine intrathecal analgesia and sufentanil PCIA in elderly patients with hip fracture undergoing single spinal anesthesia \u2014 a randomized clinical trial

BackgroundThe complications of postoperative pain, such as hypertension, hypermetabolism, irritability, and postoperative cognitive dysfunction, significantly affect the postoperative rehabilitation of elderly patients. Intrathecal morphine prolongs analgesia after surgery, but has been implicated in nausea and vomiting, pruritus, postoperative respiratory depression, or apneic episodes. The present study explored the effect and safety of low-dose morphine used adjunctively with bupivacaine during single spinal anesthesia or sufentanil patient-controlled intravenous analgesia (PCIA) in elderly patients with hip fracture surgery. Since elderly patients often need anticoagulant therapy in the early postoperative period, single spinal anesthesia was involved in completing the operation in this study.MethodsEighty elderly patients aged 70–85 years who underwent elective hip fracture surgery with single spinal anesthesia were divided into two groups, 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of morphine (morphine group, group M) and 12.5 mg of 0.5% hyperbaric bupivacaine with 100 µg of sufentanil PCIA (sufentanil group, group S). The analgesia scores using the visual analogue scale (VAS), the Brinell comfort scale (BCS) were evaluated at 6, 12, 24, and 48 h after operation, and adverse reactions were recorded such as nausea and vomiting, pruritus, sedation, respiratory depression, and POD (postoperative delirium) with Delirium Rating Scale-r 98.ResultsWithin 24 h after operation, the analgesic and BCS scores of group M were better than those of group S (P < 0.05). Group M had higher frequency of skin pruritus than group S within 24 h, and the difference was statistically significant. The incidence of POD in group M (2 cases) was lower than that in group S (6 cases) (5.71% vs 18.18%) (P < 0.05) with the DRS-r 98 scores. No significant difference was observed in nausea and vomiting between the two groups, and the difference of severe respiratory depression was not found in both groups.ConclusionCompared with sufentanil PCIA, low-dose intrathecal morphine has a satisfactory analgesic effect, and little effect on the patient's cognitive function with low medical cost. Under effective respiratory monitoring, it can be used safely and effectively in elderly patients with hip fracture.Trial registrationRegistered with the Chinese Clinical Trial Registry under ChiCTR2100042706. 26/01/2021.

Effect of wrist-ankle acupuncture on propofol dosage during painless colonoscopy: A randomized controlled prospective study

BACKGROUNDThe clinical advantages of painless colonoscopy can reduce the fear and discomfort of patients and increase the detection rate of diseases. Propofol has the characteristics of fast effect and short action time. It is a common choice for painless endoscopic sedation and anesthetics. However, propofol can cause severe respiratory and circulatory depression. Therefore, it is important to find a way to reduce the dose of propofol.AIMTo explore the effect of wrist-ankle acupuncture on propofol dose during colonoscopy. METHODSTwo hundred patients who were going to receive selective painless colonoscopy in Hebei Hospital of Traditional Chinese Medicine were selected and divided into wrist-ankle acupuncture group (WAA group, n = 100) and control group (CON group, n = 100). After entering the operation room, patients were given 0.025 mg/kg nabufine intravenously and propofol at the initial dose of 0.5 mg/kg. In patients who did not fall asleep, propofol (10 mg/time) was given until loss of consciousness. Prior to anesthesia, patients in WAA group were punctured by specialist in the inferior 1, 2 and 3 regions according to the zoning principle of wrist-ankle acupuncture. The primary endpoint was required dose of propofol, and the secondary endpoints were the incidence of hypoxemia and hypotension. Furthermore, the following data were recorded: The operation time, wake-up time, incidence of nausea and vomiting, incidence of abdominal distention, post-colonoscopy pain, examiners' satisfaction, patients' satisfaction and Borg fatigue index. This study has been registered in the Chinese Clinical Trial Registry (Registration Code: ChiCTR1900022177).RESULTSThe induced dose of propofol and the total dose of propofol in WAA group were 80 mg and 110 mg, respectively, which were significantly lower than those in CON group (P < 0.05). The incidences of hypoxemia and hypotension in the WAA group were 2.2% and 3.3%, respectively, significantly lower than those in the CON group (P < 0.05). The incidence of abdominal distension in the WAA group was 8.8%, which was significantly lower than that in the CON group (P < 0.05, 28.9%). The waking time of WAA group was 3.26 ± 0.87 min, which was significantly lower than that of CON group (6.06 ± 0.88 min, P < 0.05).CONCLUSIONWrist-ankle acupuncture can reduce the induction dose and total dose of propofol as well as the incidence of adverse reactions in painless colonoscopy without affecting the satisfaction of examiners and patients. This procedure is simple in operation and easy to promote in clinical practice.

Prevalence of Gabapentinoids and Central Nervous System Depressant Drugs, and Their Association with Risk Factors for Respiratory Depression in Primary Care Patients.

Warnings have been published regarding an increased risk of severe respiratory depression in patients receiving gabapentinoids either alone or in combination with opioids and/or anxiolytics/hypnotics, especially in individuals with a respiratory risk factor. The aim is to report the prevalence of the use of gabapentinoids alone and associated with central nervous system depressant drugs, and possible associated risk factors for respiratory depression, in order to identify the most fragile population and establish intervention strategies. We performed a cross-sectional study using computerized prescription records from the northern area of Barcelona at Catalan Institute of Health for 363,007 inhabitants registered during 2021. Patients aged ≥18 years with one or more gabapentinoid prescription were included. Age, gender, polypharmacy, adjusted morbidity groups, quantity of chronic diseases, and the number of consultations per year were independent variables. Four age categories were defined (18-64 years, then 64-74, 75-84, and those aged 85 years or older). Descriptive and inferential statistics were employed. Level of statistical significance was 5% (p≤0.05). For the analysis, the SPSS program (version 22) was employed. Of the study sample, 9218 were prescribed gabapentidoids. Overall prevalence of use was 3.0% (women 3.6%, men 2.4%). On the whole, women used more drugs than men. In contrast to their younger counterparts, consumption increased 2.6 times, 3.8 times, and 4.0 times in the 65-74 age group, 75-84 age group, and those aged ≥85 years, respectively. Mean age was 65.59 (±15.80) years. Polypharmacy (5-9 drugs) was present in 41.7% of the patients and extreme polypharmacy (≥10 drugs) was present in 39.3% of the patients. Regarding renal function, 2396 patients (25.9%) had glomerular filtration that required dose adjustment (76.1% with gabapentin and 23.8% with pregabalin). In 141 patients (5.9%), a total daily dose higher than that authorized (109 with gabapentin, 29 with pregabalin) had been prescribed. The prescription of gabapentinoids combined with opioids and/or anxiolytics/hypnotics was significantly associated with (i) polypharmacy (5-9 drugs, OR: 3.42 [95% CI 3.00-3.88]; ≥10 drugs, OR 8.72 [95% CI 7.42-10.25]); (ii) quantity of chronic diseases, OR: 1.14 (95% CI 1.11-1.17); (iii) augmented number of consultations/year, OR: 1.01 (95% CI 1.00-1.01); (iv) female gender, OR: < 1 for men, OR: 0.66 (95% CI 0.60-0.73); (v) being elderly: 65-74 years, OR: 0.71 (95% CI 0.62-0.81); 75-84 years, OR: 0.62 (95% CI 0.54-0.71); ≥85 years, OR: 0.68 (95% CI 0.58-0.81); and (vi) adjusted morbidity groups, OR: 0.90 (95% CI 0.88-0.92), (p< 0.0001). Exposure to gabapentinoids occurs in a non-negligible percentage of the population. Greater numbers of combinations of gabapentinoids and opioids and/or anxiolytics/hypnotics were associated with polypharmacy, quantity of chronic diseases, and augmented number of consultations, but not with male gender, older age, and adjusted morbidity groups.

Nocturnal Oxygen Desaturation Index Correlates with Respiratory Depression in Post-Surgical Patients Receiving Opioids - A Post-Hoc Analysis from the Prediction of Opioid-Induced Respiratory Depression in Patients Monitored by Capnography (PRODIGY) Study.

PurposePostoperative monitoring of respiratory status on general care wards typically consists of intermittent checks of oxyhemoglobin saturation and respiratory rate, allowing substantial unmonitored time for severe opioid induced respiratory depression (RD) to develop unnoticed. Oxygen desaturation index (ODI) can be computed solely by continuous pulse oximetry monitoring. In this post-hoc analysis, we evaluate whether nocturnal ODI correlates with RD.Patients and MethodsThe PRODIGY trial (NCT02811302) was a multinational study conducted where adult patients receiving parenteral opioids on the general care floor were continuously monitored by blinded pulse oximetry and capnography monitoring to detect episodes of RD. An RD episode was defined as: respiratory rate ≤5 breaths/min (bpm) for ≥3 minutes, oxygen saturation (SpO2) ≤85% for ≥3 minutes, end-tidal carbon dioxide (EtCO2) ≤15 or ≥60 mm Hg for ≥3 minutes, apnea episode lasting >30 seconds, or any respiratory opioid-related adverse event. Data were used to calculate nocturnal (00:00 ─ 06:00) ODI4% based on desaturation episodes (4% decrease from mean oxyhemoglobin saturation in the past 120 seconds, lasting ≥10 seconds). Continuous monitoring began after a patient received parenteral opioids, allowing identification of potential RD and ODI4% episodes during opioid therapy. The average number of ODI4% episodes (≥1, ≥5, ≥10, ≥15 episodes/hour) were analyzed. Logistic regression and area under the receiver operating characteristic curve (AUC) were computed.ResultsA final cohort of 1072 (out of 1335) patients had sufficient data, with 76% (N=817/1072) having ≥1 episode of ODI4%. Multivariable logistic regression showed that ODI4% was strongly associated with RD, with greater risk for higher ODI4% scores: ≥5 episodes/hour odds ratio 2.59 (95% CI 1.72–3.89, p<0.0001); ≥10 episodes/hour 3.39 (95% CI 1.80–6.39, p=0.0002); ≥15 episodes/hour 4.71 (95% CI 1.93–11.47, p=0.0006).There was no significant association between ODI4% and respiratory adverse events.ConclusionNocturnal ODI4% was highly correlated with RD among hospitalized patients receiving parenteral opioids. Patients with a high ODI4%, especially with ≥15 episodes/hour, are more likely to experience RD and should be evaluated for the need of closer monitoring after opioid administration.

Vitamin D Deficiency in Critically Ill Children in Karachi

Objective: To evaluate vitamin D levels in critically ill children. Subject and methods: There were 114 critical ill patients, who were admitted in pediatric ICU with severe respiratory depression (sat &lt; 90%), infection (WBC &gt; 10X 103), myocarditis (EF &lt; 40%). Blood sample was drawn for evaluation of vitamin D levels. Results:- The average age of the children was 4.95±2.7 years. There were 63(55.26%) male and 51(44.74%) female. Frequency of vitamin D deficiency in critically ill patients was observed in 55.26% (63/114) children. Conclusion: - In our study, critically ill children had higher frequency of vitamin D deficiency. Keywords: Vitamin D, Critically ill patients, Infection, 25(OH) D levels

Pre-treatment with Tandospirone attenuates fentanyl-induced respiratory depression without affecting the analgesic effects of fentanyl in rodents

Opioid analgesics are widely used to treat acute, postoperative, and chronic pain. However, opioid receptor activation can result in severe respiratory depression. In this study, we demonstrated that Tandospirone (TS), a selective serotonin-1A receptor partial agonist, is effective against opioid-induced respiratory depression. Fentanyl was used to establish a respiratory depression model in rodents. We observed the effects of TS on respiratory depression in rats by using plethysmographic recordings and arterial oxygen saturation. In addition, we evaluated the effects of TS on fentanyl-induced sedation and analgesia by using the loss of righting reflex (LORR) and hot-plate tests, respectively. Rats (n = 5) were treated with TS or saline 5 min prior to fentanyl administration. TS [2 mg/kg, intravenous (i.v.)] dose-dependently attenuated fentanyl-induced respiratory depression versus saline + fentanyl group. Furthermore, pre-treatment with TS (2 mg/kg, i.v.) increased arterial oxygen saturation to 76.5 ± 2.0% at 5 min after fentanyl injection, compared with 35.9 ± 2.5% in saline pre-treated rats (P < 0.001), whereas the time to induction of LORR (P > 0.99) and duration of LORR (P = 0.95) did not differ between the “TS + fentanyl” and “saline + fentanyl” group. The antinociceptive effect of fentanyl was not affected by the administration of TS (P = 0.99) in mice (n = 10). In conclusion, we found that TS, a novel non-benzodiazepine anxiolytic/antidepressant drug, could attenuate severe fentanyl-induced respiratory depression and did not affect the analgesic/sedative effect of fentanyl. The clinical application of TS could significantly improve pain management.