CYX-5, a G-protein biassed MOP receptor agonist, DOP receptor antagonist and KOP receptor agonist, evokes constipation but not respiratory depression relative to morphine in rats.

BACKGROUND: Strong opioid analgesics such as morphine alleviate moderate to severe acute nociceptive pain (e.g. post-surgical or post-trauma pain) as well as chronic cancer pain. However, they evoke many adverse effects and so there is an unmet need for opioid analgesics with improved tolerability. Recently, a prominent hypothesis has been that opioid-related adverse effects are mediated by ß-arrestin2 recruitment at the µ-opioid (MOP) receptor and this stimulated research on discovery of G-protein biassed opioid analgesics. In other efforts, opioids with MOP agonist and δ-opioid (DOP) receptor antagonist profiles are promising for reducing side effects c.f. morphine. Herein, we report on the in vivo pharmacology of a novel opioid peptide (CYX-5) that is a G-protein biassed MOP receptor agonist, DOP receptor antagonist and kappa opioid (KOP) receptor agonist. METHODS: Male Sprague-Dawley received intracerebroventricular bolus doses of CYX-5 (3, 10, 20 nmol), morphine (100 nmol) or vehicle, and antinociception (tail flick) was assessed relative to constipation (charcoal meal and castor oil-induced diarrhoea tests) and respiratory depression (whole body plethysmography). RESULTS: CYX-5 evoked naloxone-sensitive, moderate antinociception, at the highest dose tested. Although CYX-5 did not inhibit gastrointestinal motility, it reduced stool output markedly in the castor oil-induced diarrhoea test. In contrast to morphine that evoked respiratory depression, CYX-5 increased tidal volume, thereby stimulating respiration. CONCLUSION: Despite its lack of recruitment of ß-arrestin2 at MOP, DOP and KOP receptors, CYX-5 evoked constipation, implicating a mechanism other than ß-arrestin2 recruitment at MOP, DOP and KOP receptors, mediating constipation evoked by CYX-5 and potentially other opioid ligands.

Peripheral Administration of Selective Glycine Transporter-2 Inhibitor, Oleoyl-D-Lysine, Reverses Chronic Neuropathic Pain but Not Acute or Inflammatory Pain in Male Mice.

Aberrations in spinal glycinergic signaling are a feature of pain chronification. Normalizing these changes by inhibiting glycine transporter (GlyT)-2 is a promising treatment strategy. However, existing GlyT2 inhibitors (e.g., ORG25543) are limited by narrow therapeutic windows and severe dose-limiting side effects, such as convulsions, and are therefore poor candidates for clinical development. Here, intraperitoneally administered oleoyl-D-lysine, a lipid-based GlyT2 inhibitor, was characterized in mouse models of acute (hot plate), inflammatory (complete Freund's adjuvant), and chronic neuropathic (chronic constriction injury) pain. Side effects were also assessed on a numerical rating score, convulsions score, for motor incoordination (rotarod), and for respiratory depression (whole body plethysmography). Oleoyl-D-lysine produced near complete antiallodynia for chronic neuropathic pain, but no antiallodynia/analgesia in inflammatory or acute pain. No side effects were seen at the peak analgesic dose, 30 mg/kg. Mild side effects were observed at the highest dose, 100 mg/kg, on the numerical rating score, but no convulsions. These results contrasted markedly with ORG25543, which reached less than 50% reduction in allodynia score only at the lethal/near-lethal dose of 50 mg/kg. At this dose, ORG25543 caused maximal side effects on the numerical rating score and severe convulsions. Oleoyl-D-lysine (30 mg/kg) did not cause any respiratory depression, a problematic side effect of opiates. These results show the safe and effective reversal of neuropathic pain in mice by oleoyl-D-lysine and provide evidence for a distinct role of glycine in chronic pain over acute or short-term pain conditions. SIGNIFICANCE STATEMENT: Partially inhibiting glycine transporter (GlyT)-2 can alleviate chronic pain by restoring lost glycinergic function. Novel lipid-based GlyT2 inhibitor ol-D-lys is safe and effective in alleviating neuropathic pain, but not inflammatory or acute pain. Clinical application of GlyT2 inhibitors may be better suited to chronic neuropathic pain over other pain aetiologies.

Toxicity assessment of gelsenicine and the search for effective antidotes.

BACKGROUND: Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth (G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. OBJECTIVE: This study aimed to analyse the toxicity characteristics of gelsenicine. METHODS: Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. RESULTS: In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood-brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. CONCLUSIONS: Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine-related poisoning and its toxicity mechanisms.

Auxora for the Treatment of Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome: Clinical Development of a Calcium Release-Activated Calcium Channel Inhibitor.

OBJECTIVES: To assess the safety of Auxora in patients with acute pancreatitis (AP), systemic inflammatory response syndrome (SIRS), and hypoxemia, and identify efficacy endpoints to prospectively test in future studies. METHODS: This phase 2, open-label, dose-response study randomized patients with AP, accompanying SIRS, and hypoxemia (n = 21) to receive low-dose or high-dose Auxora plus standard of care (SOC) or SOC alone. All patients received pancreatic contrast-enhanced computed tomography scans at screenings, day 5/discharge, and as clinically required 90 days postrandomization; scans were blinded and centrally read to determine AP severity using computed tomography severity index. Solid food tolerance was assessed at every meal and SIRS every 12 hours. RESULTS: The number of patients experiencing serious adverse events was not increased with Auxora versus SOC alone. Three (36.5%) patients with moderate AP receiving low-dose Auxora improved to mild AP; no computed tomography severity index improvements were observed with SOC. By study end, patients receiving Auxora better tolerated solid foods, had less persistent SIRS, and had reduced hospitalization versus SOC. CONCLUSIONS: The favorable safety profile and patient outcomes suggest Auxora may be an appropriate early treatment for patients with AP and SIRS. Clinical development will continue in a randomized, controlled, blinded, dose-ranging study.

A cautionary tale of pyridoxine toxicity in cystathionine beta-synthase deficiency detected by two-tier newborn screening highlights the need for clear pyridoxine dosing guidelines.

Classic homocystinuria is due to deficiency of cystathionine beta-synthase (CBS), a pyridoxine-dependent enzyme that, depending on the molecular variants, may be co-factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two-tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co-factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high-dose pyridoxine to determine responsiveness. Here we describe our NBS-identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight-based dosing and duration recommendations for pyridoxine challenge in neonates.

An unusual cause of high density radiological opacities.

INTRODUCTION: Metallic mercury poisoning through intravenous injection is rare, especially as part of a suicide attempt. Diagnosis and treatment of the disease are challenging as clinical features are not specific. MATERIAL AND METODS: A 41-year-old male presented with dyspnea, fatigue, loss of weight, and loss of appetite over two months. Routine radiological examination by chest X-ray and CT showed randomly distributed high density opacities with Hounsfield units (HU) around 500 HU all over the body. The diagnosis was then confirmed with a urinary mercury concentration of > 1000 mcg/24 h. RESULTS: The patient's clinical condition was getting worse in spite of chelation therapy and hemodialysis. The patient eventually died because of respiratory failure. CONCLUSION: Early diagnosis and appropriate treatment are critical for intravenous mercury poisoning especially because there are no specific signs or symptoms. There should be a high level of suspicion in drug abusers. Treatment should involve the combined use of chelating agents and other treatments such as hemodialysis and plasma exchange in advanced clinical settings.

Evolving pediatric epidural practice: An institution's clinical experience over 20 years-A retrospective observational cohort study.

BACKGROUND AND OBJECTIVES: Epidural analgesia is an effective, established perioperative intervention in all age-groups. In children, however, epidural-related data are limited compared to the adult population. The aim of this study was to examine the use of pediatric epidural analgesia in our institution and, thereby, add to the existing data pool. METHODOLOGY: Patients who received epidural analgesia as part of their perioperative management between 1996 and 2016 at Great Ormond Street Hospital, London, UK, were studied to determine how epidural practice has changed over time, associated incidence of serious adverse events, complications, and patient/parent satisfaction. Epidural use and monitoring were in accordance with standard hospital protocols. Data were prospectively collected and entered into a secure database by trained personnel. These data were subsequently extracted for retrospective analysis. RESULTS: A total of 3876 patients were included. The median age was 4.4 years (range 1 day to 20 years), and the median weight was 20.3 kg. Across all age-groups, the lumbar region was the most common site of epidural insertion while urology (42.2%) and general surgery (37.3%) were the specialities for which it was most utilized. Over the study period, the number of epidurals performed declined while the number of surgical procedures performed simultaneously increased. The infusate most commonly used was local anesthetic with preservative-free morphine (71.9%). In 923 (23.2%) patients, systemic opioids were additionally used for analgesic management by means of patient-controlled analgesia or nurse-controlled analgesia. There was one serious adverse event in the form of permanent nerve injury, giving an overall incidence of approximately 1:3800. Other complications included postoperative nausea and vomiting (35.9%), urinary retention (4.4%), and pruritus (31%). Overall global satisfaction with the service was generally high, with 95% providing a rating of "very good" or "good." CONCLUSION: This study evaluated two decades of epidural practice in our institution. Epidural analgesia remains a safe, effective option for postoperative analgesia, but its use has declined over time, and this trend is likely to continue. Rates of serious adverse events and complications were low and comparable to those published in other similar studies. Global satisfaction among patients/parents remains high.

[Acute Respiratory Failure after Silicone Injection]. / Akutes respiratorisches Versagen durch Silikon-Injektion.

A 35-year-old male patient presented to the emergency department with complains of fever, dyspnea and petechiae. The chest X-ray revealed signs of bipulmonary infiltration. 5 days ago, an illicit silicone injection was performed into the penis for cosmetic reasons. Due to progressive respiratory failure the patient required mechanical ventilation. Bronchoalveolar lavage revealed diffuse alveolar hemorrhage. Silicone pneumonitis with a severe acute respiratory failure based on silicone embolization syndrome was diagnosed. Prone positioning, lung-protective ventilation and corticosteroid therapy were initiated. The patient was discharged from ICU after 19 days. In an outpatient follow up, lung function was fully recovered. CONCLUSION: Silicone pneumonitis should be considered in case of fever, respiratory distress and alveolar hemorrhage linked to cosmetic procedures. High dose corticosteroid therapy and lung-protective ventilation strategies may help for complete recovery of lung function.

Anticoagulant rodenticide toxicosis causing tracheal collapse in 4 small breed dogs.

OBJECTIVE: To describe 4 cases of tracheal narrowing attributed to tracheal mucosal hemorrhage caused by anticoagulant rodenticide toxicity in breeds predisposed to tracheal collapse. CASE SUMMARY: Over the years 2005-2014, 4 dogs were presented for respiratory distress secondary to diffuse tracheal narrowing. All dogs had possible anticoagulant rodenticide ingestion and prolonged prothrombin time. All dogs received fresh-frozen plasma transfusions, vitamin K1 supplementation, and supportive care. Tracheal narrowing improved on follow-up radiographs in 3 of 4 patients. One of 4 did not have follow-up radiographs performed. All dogs survived. NEW OR UNIQUE INFORMATION PROVIDED: Anticoagulant rodenticide toxicity causing clinical signs consistent with tracheal collapse is a rare but recognized phenomenon that has not been previously reported in breeds prone to tracheal collapse.

Respiratory Failure Due To Plant Poisoning: Nicotiana glauca Graham.

BACKGROUND: Cases of human poisoning associated with Nicotiana glauca Graham are quite rare. Patients may consume the plant by mistaking it for spinach or use it as a folk remedy. The toxin stimulates the acetylcholine receptors in the central and autonomic nervous systems. A prompt and appropriate supportive treatment is crucial for survival. CASE REPORT: A 72-year-old female with a known breast cancer was brought to our emergency department (ED) with complaints of nausea and vomiting. The patient stated that her complaints started 2 h after she had cooked and eaten a plant in the hopes that it would help cure her cancer. On the second hour after arrival, the patient became confused. It was observed that the chest wall movements had decreased and that the patient had difficulty breathing. Due to respiratory failure, orotracheal intubation was performed to secure the airway. A sample of the plant that was eaten was requested from the patient's relatives. According to an Internet search, the plant sample was identified as N. glauca Graham. The patient was diagnosed with N. glauca Graham poisoning. The patient was extubated after 30 h. On 3-month follow-up, the patient was neurologically intact and had no complaints related to poisoning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients with incurable diseases such as cancer tend to try folk remedies and can end up in ED. In patients who present with muscle paralysis and respiratory failure, emergency physicians should consider N. glauca Graham as a cause of plant poisoning.

Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study.

BACKGROUND: Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality. METHODS AND FINDINGS: We conducted a population-based nested case-control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily), moderate (900 to 1,799 mg daily), or high (≥1,800 mg daily). A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID) use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256) and 6.8% of controls (313 of 4,619) were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI 1.61 to 2.47, p < 0.001; adjusted OR [aOR] 1.49, 95% CI 1.18 to 1.88, p < 0.001) compared to opioid prescription alone. In the dose-response analysis, moderate-dose (OR 2.05, 95% CI 1.46 to 2.87, p < 0.001; aOR 1.56, 95% CI 1.06 to 2.28, p = 0.024) and high-dose (OR 2.20, 95% CI 1.58 to 3.08, p < 0.001; aOR 1.58, 95% CI 1.09 to 2.27, p = 0.015) gabapentin use was associated with a nearly 60% increase in the odds of opioid-related death relative to no concomitant gabapentin use. As expected, we found no significant association between co-prescription of opioids and NSAIDs and opioid-related death (OR 1.11, 95% CI 0.98 to 1.27, p = 0.113; aOR 1.14, 95% CI 0.98 to 1.32, p = 0.083). In an exploratory analysis of patients at risk of combined opioid and gabapentin use, we found that 46.0% (45,173 of 98,288) of gabapentin users in calendar year 2013 received at least 1 concomitant prescription for an opioid. This study was limited to individuals eligible for public drug coverage in Ontario, we were only able to identify prescriptions reimbursed by the government and dispensed from retail pharmacies, and information on indication for gabapentin use was not available. Furthermore, as with all observational studies, confounding due to unmeasured variables is a potential source of bias. CONCLUSIONS: In this study we found that among patients receiving prescription opioids, concomitant treatment with gabapentin was associated with a substantial increase in the risk of opioid-related death. Clinicians should consider carefully whether to continue prescribing this combination of products and, when the combination is deemed necessary, should closely monitor their patients and adjust opioid dose accordingly. Future research should investigate whether a similar interaction exists between pregabalin and opioids.

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

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

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

BACKGROUND: Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. OBJECTIVES: We present a case of intravenous poison hemlock injection encountered in the emergency department. CASE REPORT: We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. CONCLUSION: Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

Multimodal Analgesic Therapy With Gabapentin and Its Association With Postoperative Respiratory Depression.

BACKGROUND: Gabapentinoids are widely used in perioperative multimodal analgesic regimens. The primary aim of this study was to determine whether gabapentin was associated with respiratory depression during phase-I postanesthesia recovery after major laparoscopic procedures. METHODS: We retrospectively reviewed the electronic health records of 8567 patients who underwent major laparoscopic procedures (lasting ≥90 minutes) from January 1, 2010, to July 31, 2014. We assessed potential associations among patient and perioperative variables and episodes of respiratory depression during phase-I recovery. Multivariable and propensity score-matched analyses were performed to assess potential associations between preoperative gabapentin use and postoperative respiratory depression. RESULTS: The incidence of respiratory depression was 153 (95% confidence interval [CI], 146-161) episodes per 1000 cases. Multivariable analysis showed that gabapentin was associated with respiratory depression (odds ratio [OR], 1.47 [95% CI, 1.22-1.76]; P < .001). These results were confirmed by propensity score-matched analysis among a subset of patients who did not have analgesia supplemented by intrathecal opioids (OR, 1.26 [95% CI, 1.02-1.58]; P = .04). Older patients and those who received more intraoperative opioids had increased risk of respiratory depression. Those who had an episode of respiratory depression had a longer phase-I recovery (P < .001) and an increased rate of admission to a higher level of care (P = .03). CONCLUSIONS: The use of gabapentin is associated with increased rates of respiratory depression among patients undergoing laparoscopic surgery. When gabapentinoids are included in multimodal analgesic regimens, intraoperative opioids must be reduced, and increased vigilance for respiratory depression may be warranted, especially in elderly patients.

Patient's death as a result of mistakenly injection of pancuronium.

Pancuronium is a typical non-depolarizing, curare-mimetic, very potent muscle relaxant. Besides application in anesthesiology and intensive care, it is used in execution as a part of lethal injection. In medico-legal practice, there are cases of using this substance in order to commit suicide or to deprive other people of their lives. Accidental pancuronium intoxications are very rare. The authors present such case ended in sudden death of hospitalized woman after mistakenly injection of the drug. 57-year-old female alcoholic was admitted to the Acute Poisoning Centre after ethylene glycol ingestion. During the fifth day of treatment the nurse by mistake, instead of furosemide, intravenously administered her pancuronium. Sudden respiratory and circulatory arrest occurred, so she was intubated and resuscitation with artificial ventilation were undertaken, however within 1 hour and 45 minutes the patient died. Due to the vague background of a sudden deterioration in the patient's condition, the case was brought for prosecution. The autopsy and histopathological studies did not reveal the cause of death, but undertaken chemico-toxicological examinations identified the presence of pancuronium in blood, liver and kidney (190 ng/ml, 70 ng/g and 125 ng/g, respectively). Chemico-toxicological analysis proved that the cause of death of the 57-year-old hospitalized woman was pancuronium intoxication due to evident medical error during drug administration. In our case the concentration of pancuronium in blood was in therapeutic range (200-600 ng/ml). However, even a therapeutic pancuronium dose administered to patient the breath of whom is not supported and monitored can be a threat to his life.

Inadvertent Methylergonovine Administration to a Neonate.

BACKGROUND Methylergonovine is an ergot alkaloid used to treat post-partum hemorrhage secondary to uterine atony. Mistaking methylergonovine for vitamin K with accidental administration to the neonate is a rare iatrogenic illness occurring almost exclusively in the delivery room setting. Complications of ergot alkaloids in neonates include respiratory depression, seizures, and death. CASE REPORT A term infant was inadvertently given 0.1 mg of methylergonovine intramuscularly in the right thigh. The error was only noted when the vial of medication was scanned, after administration, identifying it as methylergonovine rather than vitamin K. The local poison center was notified, and the infant was transferred to the neonatal intensive care unit for observation. Two hours after transfer, the infant was noted to have oxygen desaturations and required oxygen via nasal cannula. Supplemental oxygen was continued for 4 hours until the neonate was able to maintain normal oxygen saturations in room air. Feeding was started by 10 hours of life, and the infant was discharged home in good condition after a 72-hour stay without further complications. CONCLUSIONS Because of the potential for serious adverse events, vigilance is required to prevent accidental administration of methylergonovine to the neonate as a result of possible confusion with vitamin K in the early post-partum period.

Fish Oil Supplementation Enhances Pulmonary Strength and Endurance in Women Undergoing Chemotherapy.

We investigated the effect of fish oil (FO) supplementation, at 4 g/day, on the respiratory performance and blood lipid profile of 32 patients with breast cancer at the beginning of chemotherapy. They were randomized into two groups: control (C) and FO supplemented (S). Both groups underwent three respiratory evaluations and blood harvest (before chemotherapy-Day 0, and 30 and 60 days after supplementation). The S group showed a significant increase in the maximal inspiratory and expiratory pressure (P ≤ 0.05 vs. Day 0) and in the maximum voluntary ventilation (P ≤ 0.05). In the treadmill 6-min-walk test, the S group had a significant increase in the walked distance (P ≤ 0.05). Blood lactate concentration was significantly lower in the S group after 60 days, at rest, when compared to C (P ≤ 0.05). Plasma high-density lipoprotein (HDL) cholesterol concentration remained the same after 60 days of supplementation, while in the C group, it decreased significantly (P ≤ 0.05 Day 0 vs. Day 60). Triacylglycerol (TAG) plasma concentration in the S group was lower when compared to the C group (P ≤ 0.05 Day 60S vs. Day 60). Supplementation with FO caused improvement in the respiratory muscle strength and endurance, ameliorated functional performance, and kept TAG, HDL cholesterol, and lactate plasma concentration at normal levels.

Continuous negative external pressure (cNEP) reduces respiratory impairment during screening colonoscopy: a pilot study.

BACKGROUND AND STUDY AIMS: Drugs administered during gastrointestinal procedures cause increased collapsibility of the upper airway, which may lead to respiratory impairment. We evaluated the ability of continuous negative external pressure (cNEP) to lessen respiratory impairment during screening colonoscopy. PATIENTS AND METHODS: The initial 24 patients served as controls, while the next 30 received cNEP. cNEP was delivered by a soft silicone collar placed over the anterior neck. The primary endpoint was the frequency of respiratory impairment, defined as either: (i) a decline from baseline of > 4 % in oxygen saturation, or (ii) apnea lasting ≥ 20 seconds. RESULTS: Mean respiratory impairment episodes were 3.50 in the no-cNEP group vs. 1.92 in the cNEP group, a reduction of 45 % (P = 0.022). Apneas ≥ 20 seconds occurred in 74 % of the no-cNEP group and 28 % of the cNEP group (P = 0.002). While 42 % of the no-cNEP group required increased supplemental oxygen, this was true for only 10 % of the cNEP group (P = 0.01). cNEP adverse events were minimal. CONCLUSIONS: During screening colonoscopy, sedation-related respiratory impairment is significantly reduced by cNEP.ClinicalTrials.gov NCT01895062.