piperidines and Respiratory-Insufficiency

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

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The present study summarizes the knowledge to date of the use of remifentanil in obstetric anaesthesia and analgesia.. Modest labour analgesia, particularly for the first stage, can be achieved using a patient-controlled analgesia bolus of 40 microg with a 2-min lockout. Neonatal effects are minimal; however, maternal desaturation is a possibility and requires one-to-one supervision and appropriate monitoring. Background infusions can improve analgesia, but maternal desaturation or even apnoea is more likely. Remifentanil is effective at obtunding responses to airway manipulation and surgery under general anaesthesia. Neonatal effects are more pronounced and 50% of neonates may need assisted ventilation, and occasionally naloxone.. Remifentanil has a place in obstetric anaesthesia and analgesia. Further studies are needed to confirm if background infusions are safe in addition to patient-controlled analgesia. Studies are needed to establish a dose range under general anaesthesia that prevents neonatal respiratory depression at birth.

Topics: Analgesia, Obstetrical; Analgesia, Patient-Controlled; Anesthesia, Epidural; Anesthesia, General; Anesthetics, Intravenous; Female; Humans; Infant, Newborn; Oxygen; Piperidines; Pregnancy; Remifentanil; Respiratory Insufficiency; Treatment Outcome

Remifentanil is the newest of the fentanyl family of short-acting phenylpiperidine derivatives to be released into clinical practice. Remifentanil is a pure agonist at the mu opioid receptor with relatively little binding at the kappa, sigma or delta receptors. This is precisely the same profile as the other opioids currently popular in anaesthetic practice (fentanyl, alfentanil, sufentanil) and it offers the same advantages (profound analgesia, sedation, attenuation of the stress response). This has led to widespread use of remifentanil as an adjunct to general anaesthesia in a variety of clinical settings. The unique pharmacology of remifentanil, in particular its rapid offset, has more recently attracted clinicians and investigators to the use of remifentanil by bolus injection, especially for procedures requiring a brief, intense, opioid effect. The clinical effects of remifentanil, both therapeutic and adverse, are consistent with that of the other fentanyl congeners. However, the pharmacokinetic profile of remifentanil, that is, its rapid effect site equilibration, has also revealed a significant potential for therapeutic misadventure. The untoward effects of remifentanil, given by continuous infusion, are well-described in the literature. They are predictable and easily managed by experienced clinicians. This review will concentrate on the adverse effects of remifentanil given by bolus injection, either alone or in the context of a background infusion.

Topics: Analgesics, Opioid; Heart Rate; Humans; Injections, Intravenous; Muscle Rigidity; Piperidines; Remifentanil; Respiratory Insufficiency; Safety; Seizures

Remifentanil is a synthetic opioid that was developed in the early 1990s and introduced into clinical use in 1996. It is a methyl ester and is metabolised by nonspecific tissue and plasma esterases. Consequently, it is a drug that undergoes rapid elimination and has a reported terminal elimination half-life of between 10 and 35 minutes. Because there is no drug accumulation, the context-sensitive half-time remains constant; thus the pharmacokinetics of the drug do not change regardless of the duration of infusion. The organ-independent elimination of remifentanil, coupled with the fact that its clearance is greater in infants and neonates compared with older age groups, make its pharmacokinetic profile different from any other opioid. In addition, its unique metabolism confers predictability in its clinical use. Like other opioid mu receptor agonists, remifentanil provides dose-dependent analgesia, while the adverse effects of this drug, e.g. respiratory depression, are also thought to be dose related. The incidence of nausea and vomiting appear similar to other opioids. Its rapid and consistent metabolism regardless of duration of infusion has made remifentanil an attractive analgesic/anaesthetic option for paediatric care providers.

Topics: Analgesics, Opioid; Anesthesia, General; Anesthetics, Intravenous; Blood Pressure; Child; Heart Rate; Humans; Nausea; Piperidines; Remifentanil; Respiratory Insufficiency; Seizures; Vomiting

Topics: Adolescent; Adult; Carbon Dioxide; Cross-Over Studies; Double-Blind Method; Female; Healthy Volunteers; Humans; Incidence; Male; Middle Aged; Oxygen Saturation; Piperidines; Placebos; Pruritus; Receptors, Opioid, kappa; Respiratory Insufficiency; Respiratory Rate; Young Adult

The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear.. We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed.. A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group.. Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

Topics: Adult; Aged; Antiviral Agents; Brazil; COVID-19; COVID-19 Drug Treatment; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Hospitalization; Humans; Incidence; Janus Kinase 3; Janus Kinase Inhibitors; Male; Middle Aged; Oxygen Inhalation Therapy; Piperidines; Pyrimidines; Respiratory Insufficiency

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; 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Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; 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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Using models of respiratory compromise, loss of response to esophageal instrumentation, and loss of responsiveness, the authors explored through simulation published dosing schemes for endoscopy using propofol alone and in combination with selected opioids. They hypothesized that models would predict adequate conditions for esophageal instrumentation and once drug administration is terminated, rapid return of responsiveness and minimal respiratory compromise.. Four published dosing regimens of propofol alone or in combination with opioids were used to predict the probability of loss of response to esophageal instrumentation for a 10-min procedure and the probability of respiratory compromise and return of responsiveness once the procedure had ended.. Propofol alone provided a low probability (9-20%) and propofol-opioid techniques provided a moderate probability (15-58%) of loss of response to esophageal instrumentation. Once the procedure ended, all techniques provided a high likelihood of rapid return of responsiveness (less than 3 min). Propofol-opioid techniques required more time than propofol alone to achieve a high probability of no respiratory compromise (7 vs. 4 min).. Propofol alone would likely lead to inadequate conditions for esophageal instrumentation but would provide a rapid return to responsiveness and low probability of respiratory compromise once the procedure ended. The addition of remifentanil or fentanyl improved conditions for esophageal instrumentation and had an equally rapid return to responsiveness. The time required to achieve a low probability of respiratory compromise was briefly prolonged; this is likely inconsequential given that patients are responsive and can be prompted to breathe.

Topics: Analgesics, Opioid; Anesthesia Recovery Period; Anesthetics, Combined; Anesthetics, Intravenous; Dose-Response Relationship, Drug; Drug Synergism; Esophagus; Fentanyl; Gastroscopy; Humans; Models, Statistical; Piperidines; Propofol; Reference Values; Remifentanil; Respiratory Insufficiency; Sensation; Time Factors

We aimed to observe the emergence characteristics of children tracheally extubated in deep anesthesia with sevoflurane or sevoflurane in combination with low-dose remifentanil.. We randomly allocated 50 pediatric patients undergoing elective electronic cochlear implantation to groups either receiving sevoflurane (Group S, n = 25), or sevoflurane plus low-dose remifentanil (Group SR, n = 25), during extubation from anesthesia. In Group S, subjects were tracheally extubated while breathing 1.3 times the minimal effective concentration of sevoflurane. In Group SR, subjects were tracheally extubated while breathing 1.0 times the minimal effective concentration of sevoflurane with 0.02-0.05 μg · kg(-1) per min remifentanil. Recovery characteristics and airway complications were noted.. There was no significant difference in age, weight, sex, and duration of anesthesia. The average remifentanil rate was 0.036 μg · kg(-1) per min, and compared with Group S, patients in Group SR had a lower respiratory rate (17.3 vs 20.2 per minute, P < 0.05) and a higher ETCO(2) (52.3 vs 49.4 mmHg, P < 0.05). Oral airway usage was also less frequent in Group SR (44% vs 16%, P < 0.01). Additionally, the time from extubation to spontaneous eye opening was shorter in Group SR (10.9 min vs 19.6 min, P < 0.01). Finally, six patients in Group S and five patients in Group SR had a pediatric anesthesia emergence delirium score >10.. Low-dose remifentanil in combination with sevoflurane provided rapid recovery and was safe for deep tracheal extubation in deep anesthesia in pediatric patients.

Topics: Airway Extubation; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Carbon Dioxide; Child, Preschool; Cochlear Implantation; Double-Blind Method; Female; Humans; Male; Methyl Ethers; Monitoring, Intraoperative; Oximetry; Piperidines; Remifentanil; Respiratory Insufficiency; Respiratory Mechanics; Sevoflurane

Endoscopic retrograde cholangiopancreatography ERCP is a painful and long procedure requiring transient deep analgesia and conscious sedation. An ideal anaesthetic that guarantees a rapid and smooth induction, good quality of maintenance, lack of adverse effects and rapid recovery is still lacking. This study aimed to compare safety and efficacy of a continuous infusion of low dose remifentanil plus ketamine combined with propofol in comparison to the standard regimen dose of remifentanil plus propofol continuous infusion during ERCP.. 322 ASAI-III patients, 18-85 years old and scheduled for planned ERCP were randomized. Exclusion criteria were a predictable difficult airway, drug allergy, and ASA IV-V patients. We evaluated Propofol 1 mg/kg/h plus Remifentanil 0.25 µg/kg/min (GR) vs. Propofol 1 mg/kg/h plus Ketamine 5 µg/kg/min and Remifentanil 0.1 µg/kg/min (GK). Main outcome measures were respiratory depression, nausea/vomiting, quality of intraoperative conditions, and discharge time. P≤0.05 was statistically significant (95% CI).. Respiratory depression was observed in 25 patients in the GR group compared to 9 patients in the GK group (p=0.0035). ERCP was interrupted in 9 cases of GR vs. no cases in GK; patients ventilated without any complication. Mean discharge time was 20±5 min in GK and 35±6 min in GR (p=0.0078) and transfer to the ward delayed because of nausea and vomiting in 30 patients in GR vs. 5 patients in GK (p=0.0024). Quality of intraoperative conditions was rated highly satisfactory in 92% of GK vs. 67% of GR (p=0.028).. The drug combination used in GK confers clinical advantages because it avoids deep sedation, maintains adequate analgesia with conscious sedation, and achieves lower incidence of postprocedural nausea and vomiting with shorter discharge times.

Topics: Adult; Aged; Aged, 80 and over; Analgesia; Analgesics; Blood Pressure; Cholangiopancreatography, Endoscopic Retrograde; Conscious Sedation; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Heart Rate; Humans; Ketamine; Middle Aged; Piperidines; Propofol; Remifentanil; Respiratory Insufficiency; Respiratory Rate; Statistics, Nonparametric

Remifentanil and propofol are increasingly used for short-duration procedures in spontaneously breathing patients. In this setting, it is preferable to block the response to moderate stimuli while avoiding loss of responsiveness (LOR) and intolerable ventilatory depression (IVD). In this study, we explored selected effects of combinations of remifentanil-propofol effect-site concentrations (Ces) that lead to a loss of response to esophageal instrumentation (EI), LOR, and/or onset of IVD. A secondary aim was to use these observations to create response surface models for each effect measure. We hypothesized that (1) in a large percentage of volunteers, selected remifentanil and propofol Ces would allow EI but avoid LOR and IVD, and (2) the drug interaction for these effects would be synergistic.. Twenty-four volunteers received escalating target-controlled remifentanil and propofol infusions over ranges of 0 to 6.4 ng · mL(-1) and 0 to 4.3 μg · mL(-1), respectively. At each set of target concentrations, responses to insertion of a blunt end bougie into the midesophagus (40 cm), level of responsiveness, and respiratory rate were recorded. From these data, response surface models of loss of response to EI and IVD were built and characterized as synergistic, additive, or antagonistic. A previously published model of LOR was used.. Of the possible 384 assessments, volunteers were unresponsive to EI at 105 predicted remifentanil-propofol Ces; in 30 of these, volunteers had no IVD; in 30, volunteers had no LOR; and in 9, volunteers had no IVD or LOR. Many other assessments over the same concentration ranges, however, did have LOR and/or IVD. The combinations that allowed EI and avoided IVD and/or LOR primarily clustered around remifentanil-propofol Ces ranging from 0.8 to 1.6 ng · mL(-1) and 1.5 to 2.7 μg · mL(-1), respectively, and to a lesser extent approximately 3.0 to 4.0 ng · mL(-1) and 0.0 to 1.1 μg · mL(-1), respectively. Models of loss of response to EI and IVD both demonstrated a synergistic interaction between remifentanil and propofol.. Selected remifentanil-propofol concentration pairs, especially higher propofol-lower remifentanil concentration pairs, can block the response to EI while avoiding IVD in spontaneously breathing volunteers. It is, however, difficult to block the response to EI and avoid both LOR and IVD. It may be necessary to accept some discomfort and blunt rather than block the response to EI to consistently avoid LOR and IVD.

Topics: Adult; Anesthetics, Combined; Anesthetics, Intravenous; Awareness; Chi-Square Distribution; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Synergism; Esophagus; Female; Humans; Infusion Pumps; Infusions, Intravenous; Male; Models, Statistical; Piperidines; Propofol; Remifentanil; Respiratory Insufficiency; Respiratory Rate; Sensation; Surgical Instruments; Time Factors; Utah; Young Adult

To evaluate the efficacy and safety of remifentanil as a premedication in neonates undergoing elective endotracheal intubation.. A double-blind randomised controlled trial.. Tertiary care neonatal intensive care unit.. Haemodynamically stable term and preterm neonates requiring elective endotracheal intubation.. Infants in the intervention arm received remifentanil (3 microg/kg) and normal saline placebo. The control group received fentanyl (2 microg/kg) and succinylcholine (2 mg/kg). Both groups also received atropine (20 microg/kg) as part of the premedication regime.. The primary outcome was time to successful intubation. Secondary outcomes included time to return of spontaneous respirations, oxygen saturation, heart rate and blood pressure changes during the procedure, adverse events and a survey of intubation conditions.. A total of 15 infants were randomised to each group. Baseline characteristics were similar in both groups. The median time to successful intubation was not statistically different (247 s in the remifentanil group vs 156 s in the fentanyl group, p=0.88). The intubation conditions were rated more favourably with fentanyl by the intubators. Although not statistically significant, chest wall rigidity was observed more commonly with remifentanil.. Although remifentanil is comparable to fentanyl and succinylcholine in attenuating adverse physiologic responses during neonatal intubation, muscle rigidity is a concern at doses of 3 microg/kg. Further trials are required to evaluate ideal dosing regimens and combinations of agents for use with remifentanil in neonates.

Topics: Analgesics, Opioid; Double-Blind Method; Female; Humans; Infant, Newborn; Infant, Premature; Intensive Care, Neonatal; Intubation, Intratracheal; Male; Piperidines; Premedication; Remifentanil; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency

Patient-controlled sedation (PCS) with propofol-remifentanil (PR) is associated with rapid sedation and recovery, but it is associated with a greater requirement for airway rescue than PCS with midazolam-fentanyl.. To demonstrate that respiratory depression associated with PR is more frequent during anesthesiologist-administered sedation (AAS) than during PCS.. Prospective, randomized, open-label study.. Academic medical center.. Fifty patients undergoing elective colonoscopy.. PCS or AAS using PR. All patients breathed 100% oxygen via an anesthesia mask with continuous spirometry and bispectral index (BIS).. Respiratory rate and BIS.. Colonoscopy was completed in all patients. No patient under PCS required airway rescue. Five patients under AAS required bag-mask ventilation to resolve Sao(2) (arterial oxygen saturation) less than 90% lasting longer than 30 seconds. The median BIS for the AAS group was 71.7 (range 61.06-82.34) and 88.1 (range 83.15-93.05) for the PCS group. Median respiratory rates were 5.97 (range 1.21-10.73) breaths per minute for AAS and 13.19 (range 9.54-16.84) for PCS. Respiratory rates less than 2 breaths per minute composed 28% of the procedure time for AAS, but only 5% for PCS. Patients under PCS had lower median predicted effect site concentrations for PR, but were able to achieve brief peak levels exceeding those with AAS. These differences were significant (P < .001).. Potential for bias with AAS.. Patients undergoing colonoscopy with PR are significantly more likely to require intervention for hypoventilation compared with PCS. (. NCT00868920.).

Topics: Academic Medical Centers; Adult; Aged; Analgesia, Patient-Controlled; Anesthesiology; Anesthetics, Intravenous; Colonoscopy; Conscious Sedation; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Oxygen; Piperidines; Propofol; Prospective Studies; Remifentanil; Respiratory Insufficiency

To assess the feasibility of remifentanil-based sedation in hypoxemic acute respiratory failure (HARF) patients refusing to continue noninvasive ventilation (NPPV) for intolerance to two different interfaces-helmet and total face mask.. Prospective uncontrolled clinical investigation in a 14-bed ICU of an university hospital in Italy.. Thirty-six patients with persistent severe HARF who complained of discomfort and asked for interruption of NPPV session.. Patients started sedation with remifentanil (0.025 μg kg(-1) min(-1)) and the infusion rate was increased by 0.01 μg kg(-1) min(-1) every minute to a maximum of 0.12 μg kg(-1) min(-1) to obtain patient comfort.. Twenty-two out of 36 patients (61%) with median (IQR) SAPS II score of 32 (30, 38) continued the NPPV treatment after the introduction of remifentanil infusion. In this success group, median (IQR) respiratory rate decreased from 34 (31, 37) to 24 (20, 26) min(-1) (p < 0.0001) and PaO(2)/FiO(2) ratio increased from 156 (144, 176) to 270 (210, 300) mmHg (p < 0.0001) after 1 h of NPPV with remifentanil-analgosedation either with helmet or total face mask. Fourteen patients failed to continue the noninvasive treatment and were intubated after a mean of 2.5 ± 2.3 h; they showed a respiratory rate decrease from 35 (30, 38) to 27 (25, 35) min(-1) (p = 0.02) and an inability to increase the PaO(2)/FiO(2) ratio above 180 mmHg. The ICU mortality in the failure group patients was 50 versus 14% in the NPPV success group (p < 0.05). The mean remifentanil dose administered was 0.07 ± 0.03 μg kg(-1) min(-1).. This clinical study suggests that a remifentanil-based sedation protocol can decrease the rate of failure in patients with intolerance to NPPV.

Topics: Acute Disease; Feasibility Studies; Female; Humans; Hypnotics and Sedatives; Male; Masks; Middle Aged; Pilot Projects; Piperidines; Positive-Pressure Respiration; Prospective Studies; Remifentanil; Respiratory Insufficiency; Treatment Failure; Treatment Refusal

Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia.. Centre randomised, open-label, crossover, 'real-life' study.. 15 Dutch hospitals.. Adult medical and post-surgical ICU patients with anticipated short-term (2-3 days) MV.. Patient cohorts were randomised to remifentanil-based regimen (n = 96) with propofol as required, for a maximum of 10 days, or to conventional regimens (n = 109) of propofol, midazolam or lorazepam combined with fentanyl or morphine.. Outcomes were weaning time, duration of MV, ICU-LOS, sedation- and analgesia levels, intensivist/ICU nurse satisfaction, adverse events, mean arterial pressure, heart rate. Median duration of ventilation (MV) was 5.1 days with conventional treatment versus 3.9 days with remifentanil (NS). The remifentanil-based regimen reduced median weaning time by 18.9 h (P = 0.0001). Median ICU-LOS was 7.9 days versus 5.9 days, respectively (NS). However, the treatment effects on duration of MV and ICU stay were time-dependent: patients were almost twice as likely to be extubated (P = 0.018) and discharged from the ICU (P = 0.05) on day 1-3. Propofol doses were reduced by 20% (P = 0.05). Remifentanil also improved sedation-agitation scores (P < 0.0001) and intensivist/ICU nurse satisfaction (P < 0.0001). All other outcomes were comparable.. In patients with an expected short-term duration of MV, remifentanil significantly improves sedation and agitation levels and reduces weaning time. This contributes to a shorter duration of MV and ICU-LOS.

Topics: Cross-Over Studies; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Netherlands; Piperidines; Propofol; Psychomotor Agitation; Remifentanil; Respiration, Artificial; Respiratory Insufficiency; Ventilator Weaning

Opioids are routinely omitted at the induction of general anesthesia for Caesarean delivery because of the risks of respiratory neonatal depression. The short-acting opioid remifentanil may afford advantages at the induction and surgical stimulation, without subsequent neonatal depression.. In this double-blinded study, 40 at term women undergoing elective Caesarean section and requiring general anaesthesia were allocated randomly to receive either remifentanil (0,5 microg/kg) at the induction of anaesthesia (G1, n=20) or placebo (G2, n=20). Induction of anaesthesia was performed with propofol 2 mg/kg and succinylcholine 1 mg/kg. Anaesthesia was maintained with nitrous oxide in oxygen (50/50%, v/v), propofol (100 microg/kg/min), remifentanil (0.2 microg/kg/min) and atracurium. Neonates were assessed by using Apgar scores, possible respiratory depression, with or without ventilation in the mask or intubation and umbilical cord blood gas (artery: UA and vein: UV). Values are expressed as mean values +/-SD. Pearson's Chi squared and t-test were used for statistical analysis P<0.05 was considered significant.. Maternal systolic pressure, mean pressure and heart rate were significantly higher in G1 at induction. Apgar scores, heart and respiratory rate were similar between groups. Seven episodes of respiratory depressions were noted (3 in G1, 4 in G2). Five neonates required only brief assisted ventilation by face-mask (2 in G1, 3 in G2).. Remifentanil (0.5 microg/kg) at the induction of anaesthesia in elective Caesarean section under general anaesthesia can be used without subsequent neonatal depression. However, we believe that further research is necessary to extrapolate these results to a pregnancy carrying an acutely distressed foetus.

Topics: Adult; Anesthesia, General; Anesthetics, Intravenous; Apgar Score; Blood Pressure; Cesarean Section; Double-Blind Method; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Piperidines; Pregnancy; Remifentanil; Respiratory Insufficiency

The purpose of this prospective randomized study was to assess the value of pressure support ventilation during inhalational induction with sevoflurane in adult patients.. Thirty-five adult patients, ASA I-II and scheduled for ear nose throat surgery were studied. Vital capacity induction with 8% sevoflurane in 8 L min-1 oxygen was performed. Pressure support ventilation was used in Group 1 with pressure set at 15 cmH2O. In Group 2, patients breathed spontaneously. After 2 min, sevoflurane was set to 3% and remifentanil 1 microg kg(-1) was injected over 2 min followed by an infusion of 0.1 microg kg(-1) min(-1). Two minutes after the end of the bolus, intubation was performed. Bispectral index, oxygen saturation, respiratory rate, end-tidal carbon dioxide, expired tidal volume and expired sevoflurane concentration were recorded every minute.. Eighteen patients were included in Group 1 and 17 in Group 2. Saturation, respiratory rate and end-tidal carbon dioxide were similar in the two groups. Expired tidal volume was significantly higher and bispectral index values significantly lower in Group 1. Intubating conditions were better in Group 1.. Pressure support ventilation provides both better ventilation and deeper level of anaesthesia during inhalation induction with sevoflurane.

Topics: Adult; Anesthesia, Inhalation; Anesthetics, Combined; Female; Humans; Intubation, Intratracheal; Male; Methyl Ethers; Otorhinolaryngologic Surgical Procedures; Piperidines; Positive-Pressure Respiration; Prospective Studies; Remifentanil; Respiratory Insufficiency; Respiratory Mechanics; Sevoflurane; Tidal Volume; Time Factors

Although remifentanil's short-acting pharmacokinetic profile makes it well suited for procedures during which a brief period of intense analgesia is required, setting up an infusion pump for brief procedures is inconvenient. The clinical pharmacology of remifentanil administered by bolus injection, a more convenient alternative, has not been explored in detail. The primary aim of this study was to examine the safety of single bolus doses of remifentanil in conscious, healthy, adult volunteers breathing room air. Secondary aims included the evaluation of remifentanil pharmacokinetics and analgesic effects after bolus injection and a comparison of these issues in younger vs older adults.. Using a randomized, double-blind, placebo-controlled, dose-escalation, crossover study design, 64 subjects (16 over 60 years old) received remifentanil or placebo by bolus injection in a fixed unit dose separated by a 1 h washout period. Respiratory effects were assessed using a respiratory intervention scale. Analgesic effects were assessed using pressure algometry. A population pharmacokinetic model was constructed using non-linear, mixed-effects modelling techniques based on arterial blood samples. Computer simulations were performed to illustrate the clinical application of the pharmacokinetic model.. Dose-related increases in both respiratory and analgesic effects were observed. In general, the respiratory depression observed was mild and easily treated with requests to breathe or the administration of oxygen, although the older cohort (and some younger subjects) experienced more substantial respiratory depression at lower doses. The pharmacokinetics of bolus-dose remifentanil were adequately described by a two-compartment model. The pharmacokinetic simulations illustrated the potential utility of bolus-dose remifentanil.. Bolus injection could potentially be a safe and effective means of administering remifentanil in clinical situations requiring a brief period of intense analgesia. Because some subjects, both old and young, experienced significant respiratory depression even at low doses, careful monitoring of respiratory function is essential.

Topics: Adult; Aged; Aging; Analgesics, Opioid; Anesthetics, Intravenous; Computer Simulation; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Models, Biological; Piperidines; Remifentanil; Respiratory Insufficiency

The pharmacokinetic properties of remifentanil may allow a rapid analgesic action during painful procedures and short lasting postoperative respiratory depression.. We carried out a randomized, blind, study in 60 patients to compare remifentanil (continuous i.v. infusion starting at 0.025 micro g kg(-1) min(-1)) and sufentanil (i.v. doses of 0.15 micro g kg(-1)) during extra-corporeal shock wave lithotripsy (ESWL). Pain was assessed using a numerical pain scale (0-100), and pain relief was defined as a score < or =30. Respiratory depression was defined as a ventilatory frequency less than10 breaths min(-1) on two occasions or a peripheral oxygen saturation < or =92%, or administration of naloxone.. The quality of analgesia was similar in both groups, during and after ESWL. During ESWL, there was no significant difference in respiratory depression in the remifentanil and sufentanil groups (53 vs 73%, NS). The percentage of satisfied patients (73 vs 83%, NS) and satisfied surgeons (97 vs 100%, NS) did not significantly differ between groups. After the procedure patients given remifentanil had less respiratory depression (20 vs 53%, P<0.05) and less nausea and vomiting (3 vs 20%, P<0.05).. A continuous i.v. infusion of remifentanil provided comparable analgesia and caused less respiratory depression and nausea and vomiting than i.v. boluses of sufentanil in patients undergoing extra-corporeal shock wave lithotripsy.

Topics: Adult; Aged; Aged, 80 and over; Analgesia; Analgesics, Opioid; Double-Blind Method; Female; Humans; Lithotripsy; Male; Middle Aged; Nausea; Patient Satisfaction; Piperidines; Remifentanil; Respiratory Insufficiency; Sufentanil; Vomiting

During carotid endarterectomy under regional anaesthesia, patients often require medication to control haemodynamic instability and to provide sedation and analgesia. Propofol and remifentanil are used for this purpose. However, the benefits, side-effects, and optimal dose of these drugs in such patients are unclear.. Sixty patients were included in a prospective, randomized, single blinded study. All patients received a deep cervical plexus block with 30 ml ropivacaine 0.75% and were randomized to receive either remifentanil 3 micro g kg(-1) h(-1) or propofol 1 mg kg(-1) h(-1). The infusions were started after performing the regional block and were stopped at the end of surgery. Arterial pressure, ECG, ventilatory rate, and Pa(CO(2)) were measured continuously and recorded at predetermined times. Twenty-four hours after surgery, patient comfort, and satisfaction were also evaluated.. In three patients, the infusion of remifentanil had to be stopped because of severe respiratory depression or bradycardia. No significant differences were found between the two groups in haemodynamic variables or sedative effects, but there was a significantly greater decrease in ventilatory frequency and increase in Pa(CO(2)) in the remifentanil group. The patient's subjective impressions and pain control were excellent in both groups.. As a result of the higher incidence of adverse respiratory effects with remifentanil and similar sedative effects, propofol is preferable for sedation during cervical plexus block in elderly patients with comorbid disease at the dosage used.

Topics: Aged; Aged, 80 and over; Anesthetics, Intravenous; Cervical Plexus; Conscious Sedation; Endarterectomy, Carotid; Humans; Hypnotics and Sedatives; Middle Aged; Nerve Block; Piperidines; Propofol; Prospective Studies; Remifentanil; Respiratory Insufficiency; Single-Blind Method

We have investigated the effect of four doses of remifentanil on the incidence of respiratory depression and somatic response at incision. Remifentanil was administered as a loading dose of 0.125, 0.25, 0.375 or 0.5 microgram kg-1 and at a maintenance infusion rate of 0.025, 0.05, 0.075 or 0.1 microgram kg-1 min-1, respectively, with an infusion of propofol 6 mg kg-1 h-1. Responses occurred in 88% of patients with remifentanil 0.025 microgram kg-1 min-1 compared with 30-40% in the other groups. Respiratory depression after incision increased from 6% with remifentanil 0.025 microgram kg-1 min-1 to 73% with 0.1 microgram kg-1 min-1. Increases in propofol infusion rate to 7.2-8.4 mg kg-1 h-1 produced adequate maintenance of anaesthesia. Reductions in remifentanil doses to 0.025-0.05 microgram kg-1 min-1 resulted in adequate respiration at the end of surgery in 88% of patients. Maintenance infusions of the two drugs for spontaneous ventilation are likely to be in these ranges. However, the ideal loading doses and infusion rates for induction remain to be established.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Anesthetics, Intravenous; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Humans; Male; Middle Aged; Piperidines; Propofol; Remifentanil; Respiration; Respiratory Insufficiency

Topics: Analgesics, Opioid; Humans; Piperidines; Respiratory Insufficiency

Significant individual differences have been observed in pain sensitivity and analgesic effect of opioids. Previous studies have shown that genetic factors contributed to analgesics requirement obviously. Therefore, we investigated the role of genetic polymorphisms in the sensitivity to the analgesic effect of remifentanil in this study.. One hundred thirty-seven patients undergoing gynaecological surgery were observed. Before procedures, we measured the basal pain threshold of each patient, including the pressure pain threshold and pressure pain tolerance threshold. Subsequently, patients received a continuous remifentanil infusion for 15 min at a constant rate of 0.2 μg/(kg min). The pain thresholds were measured again after the remifentanil infusion. Moreover, respiratory depression was estimated using oxygen saturation during infusion. DNA was extracted from peripheral venous blood and genotyped using SNaPshot technology.. Polymorphisms were found in genes associated with the individual variation in analgesia. Participants carrying OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, and GCH1 rs8007267 CC polymorphisms showed higher sensitivity to analgesic effect induced by remifentanil, and the participants carrying the OPRD1 rs2234918 TT showed lower sensitivity to remifentanil-related respiratory depression. Moreover, individual susceptibility to remifentanil increases with age.. Gene variation in OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, GCH1 rs8007267 CC, and OPRD1 rs2234918 TT were related to the conspicuous interindividual differences in the analgesia and respiratory depression of remifentanil, mainly by affecting the target protein receptors and relative metabolic enzymes.

Topics: Analgesics, Opioid; China; Female; Humans; Pain; Piperidines; Remifentanil; Respiratory Insufficiency

Guimarães PO, Quirk D, Furtado RH, et al.

Topics: COVID-19; Humans; Piperidines; Pyrimidines; Respiratory Insufficiency; SARS-CoV-2

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed

Topics: Adenosine Monophosphate; Alanine; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Autoantibodies; Bronchoscopy; Child; COVID-19; COVID-19 Nucleic Acid Testing; Cyclophosphamide; Dermatomyositis; Disease Progression; Fatal Outcome; Female; Humans; Hydroxychloroquine; Immunocompromised Host; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung; Lung Diseases, Interstitial; Lymphohistiocytosis, Hemophagocytic; Mediastinal Emphysema; Methylprednisolone; Piperidines; Pneumonia, Pneumocystis; Pneumothorax; Pyrimidines; Respiratory Insufficiency; Shock, Septic; Subcutaneous Emphysema; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

The efficacy of opioid administration to reduce postoperative pain is limited by respiratory depression. We investigated whether clinically relevant opioid concentrations altered the respiratory pattern in the parabrachial nucleus, a pontine region contributing to respiratory pattern generation, and compared these effects with a medullary respiratory site, the pre-Bötzinger complex.. Studies were performed in 40 young and 55 adult artificially ventilated, decerebrate rabbits. We identified an area in the parabrachial nucleus where α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid microinjections elicited tachypnea. Two protocols were performed in separate sets of animals. First, bilateral microinjections of the μ-opioid receptor agonist [D-Ala, N-MePhe, Gly-ol]-enkephalin (100 μM) into the "tachypneic area" determined the effect of maximal μ-opioid receptor activation. Second, respiratory rate was decreased with continuous IV infusions of remifentanil. The opioid antagonist naloxone (1 mM) was then microinjected bilaterally into the "tachypneic area" of the parabrachial nucleus to determine whether the respiratory rate depression could be locally reversed.. Average respiratory rate was 27 ± 10 breaths/min. First, [D-Ala, N-MePhe, Gly-ol]-enkephalin injections decreased respiratory rate by 62 ± 20% in young and 45 ± 26% in adult rabbits (both P < 0.001). Second, during IV remifentanil infusion, bilateral naloxone injections into the "tachypneic area" of the parabrachial nucleus reversed respiratory rate depression from 55 ± 9% to 20 ± 14% in young and from 46 ± 20% to 18 ± 27% in adult rabbits (both P < 0.001). The effects of bilateral [D-Ala, N-MePhe, Gly-ol]-enkephalin injection and IV remifentanil on respiratory phase duration in the "tachypneic area" of the parabrachial nucleus was significantly different from the pre-Bötzinger complex.. The "tachypneic area" of the parabrachial nucleus is highly sensitive to μ-opioid receptor activation and mediates part of the respiratory rate depression by clinically relevant administration of opioids.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Female; Male; Parabrachial Nucleus; Piperidines; Rabbits; Remifentanil; Respiratory Insufficiency; Respiratory Rate

Remifentanil is most commonly offered when neuraxial labor analgesia is contraindicated. There is no consensus regarding the optimal administration, dosing strategy, or requirements for maternal monitoring, which may pose a patient safety issue. This exploratory survey evaluated the current practices regarding remifentanil use for labor analgesia at academic centers in the United States. Of 126 obstetric anesthesia directors surveyed, 84 (67%) responded. In 2014 to 2015, an estimated 36% (95% confidence interval: 25.7-46.3) of centers used remifentanil, most of which did so less than 5 times. Some serious maternal and neonatal respiratory complications occurred, emphasizing that clinical protocols and adequate monitoring are key to ensure maternal and neonatal safety.

Topics: Academic Medical Centers; Analgesia, Obstetrical; Analgesics, Opioid; Delivery, Obstetric; Female; Humans; Infant, Newborn; Infusions, Intravenous; Piperidines; Pregnancy; Remifentanil; Respiratory Insufficiency; Surveys and Questionnaires; United States

Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3',5'-monophosphate inhibition in vitro

Topics: Acute Pain; Adenosine Monophosphate; Analgesia; Analgesics, Opioid; Animals; Computer Simulation; Constipation; Drug Design; Fentanyl; Fluorescence Resonance Energy Transfer; GTP-Binding Protein alpha Subunits; HEK293 Cells; Humans; Hydrogen-Ion Concentration; Ligands; Models, Molecular; Pain Management; Piperidines; Protein Binding; Protein Conformation; Rats; Receptors, Opioid, mu; Respiratory Insufficiency; Transfection

Respiratory depression is a common adverse effect of propofol and remifentanil. We aimed to develop a model for respiratory depressant effects of propofol with remifentanil in patients undergoing endoscopy with sedation. Data were available for 136 patients undergoing endoscopy with sedation. Participants randomly received infusions of propofol and remifentanil. Predicted plasma concentrations, outputted by infusion pumps, were available. Transcutaneous arterial pressure of carbon dioxide (pCO2) was measured. Data were analyzed using nonlinear mixed-effects modeling methods. Covariate relationships were investigated for age, noxious stimuli (endoscopy tube insertion), and A118G genotype for the µ-opioid receptor (OPRM1). Participants had a median (range) age of 64.0 (25.0-88.0) years, weight of 70.0 (35.0-98.0) kg, and height of 164.0 (147.0-190.0) cm. Seven percent were recessive homozygous for OPRM1 polymorphism. An indirect-effect model with a "modulator" compartment best described pCO2 data (P < 0.001) over a direct-effect model. Remifentanil inhibited pCO2 removal with an IC50 of 1.13 ng/ml and first-order rate constant (ke 0) of 0.28 minute(-1). Propofol affected the modulator compartment with an IC50 of 4.97 µg/ml (no effect-site compartment). Propofol IC50 and remifentanil ke 0 were reduced with increasing age. Noxious stimuli and genotype were not significant covariates. An indirect-effect model with a rebound mechanism can describe remifentanil- and propofol-induced changes in pCO2 in patients undergoing noxious procedures. The model may be useful for identifying optimal dosing schedules for these drugs in a combination that provides adequate sedation but avoids respiratory depression.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Anesthetics, Intravenous; Blood Gas Monitoring, Transcutaneous; Carbon Dioxide; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Monitoring, Intraoperative; Piperidines; Propofol; Remifentanil; Respiratory Insufficiency

Topics: Analgesia, Patient-Controlled; Anesthetics, Intravenous; Drug Interactions; Half-Life; Humans; Oxygen; Oxygen Inhalation Therapy; Piperidines; Remifentanil; Respiratory Insufficiency

A 69-year-old woman undergoing treatment for hypertension and epilepsy was scheduled to undergo cataract surgery. All preoperative examination results were within normal limits. Despite being tense, she walked to the operating room. Approximately 2 minutes after an intravenous line was established by an anesthesia resident, severe hypoxia and bradycardia developed, and she lost consciousness. Cardiopulmonary resuscitation was initiated immediately, and after 1 minute, she regained consciousness, and her breathing and circulation recovered. After admission to the intensive care unit, emergency coronary angiography was performed. The blood flow in all the coronary arteries was normal. However, a decrease in the apical left ventricular wall motion and an increase in the basal wall motion were observed. Based on these findings, Takotsubo cardiomyopathy was diagnosed. The wall motion gradually improved and the patient was discharged from the hospital on postoperative day 15. The respiratory depression and bradycardia were thought to be due to an inadvertent bolus of remifentanil. We surmised that the patient had received a slight amount of retained medication when the anesthesia resident established the intravenous line, which caused severe respiratory depression. It is important to note that adverse effects such as severe respiratory depression and bradycardia can be caused by even small doses of remifentanil.

Topics: Aged; Analgesics, Opioid; Anesthesia, General; Bradycardia; Cardiopulmonary Resuscitation; Cataract Extraction; Coronary Angiography; Electrocardiography; Epilepsy; Epinephrine; Female; Humans; Hypertension; Piperidines; Remifentanil; Respiratory Insufficiency; Takotsubo Cardiomyopathy; Vasoconstrictor Agents

There is an unmet clinical need to develop a pharmacological therapy to counter opioid-induced respiratory depression without interfering with analgesia or behavior. Several studies have demonstrated that 5-HT1A receptor agonists alleviate opioid-induced respiratory depression in rodent models. However, there are conflicting reports regarding their effects on analgesia due in part to varied agonist receptor selectivity and presence of anesthesia. Therefore the authors performed a study in rats with befiradol (F13640 and NLX-112), a highly selective 5-HT1A receptor agonist without anesthesia.. Respiratory neural discharge was measured using in vitro preparations. Plethysmographic recording, nociception testing, and righting reflex were used to examine respiratory ventilation, analgesia, and sedation, respectively.. Befiradol (0.2 mg/kg, n = 6) reduced fentanyl-induced respiratory depression (53.7 ± 5.7% of control minute ventilation 4 min after befiradol vs. saline 18.7 ± 2.2% of control, n = 9; P < 0.001), duration of analgesia (90.4 ± 11.6 min vs. saline 130.5 ± 7.8 min; P = 0.011), duration of sedation (39.8 ± 4 min vs. saline 58 ± 4.4 min; P = 0.013); and induced baseline hyperventilation, hyperalgesia, and "behavioral syndrome" in nonsedated rats. Further, the befiradol-induced alleviation of opioid-induced respiratory depression involves sites or mechanisms not functioning in vitro brainstem-spinal cord and medullary slice preparations.. The reversal of opioid-induced respiratory depression and sedation by befiradol in adult rats was robust, whereas involved mechanisms are unclear. However, there were adverse concomitant decreases in fentanyl-induced analgesia and altered baseline ventilation, nociception, and behavior.

Topics: Aging; Analgesia; Anesthetics, Intravenous; Animals; Arousal; Behavior, Animal; Brain Stem; Conscious Sedation; Fentanyl; In Vitro Techniques; Medulla Oblongata; Pain Measurement; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Respiratory Insufficiency; Serotonin 5-HT1 Receptor Agonists; Spinal Cord

Orexins (hypocretins) play a crucial role in arousal, feeding, and endocrine function. We previously reported that orexin-B activated respiratory neurons in the isolated brainstem-spinal cords of neonatal rats. We herein determined whether orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil. We recorded C4 nerve bursts as an index of inspiratory activity in a brainstem-spinal cord preparation. The preparation was superfused with a solution equilibrated with 3% sevoflurane alone for 10 min and the superfusate was then switched to a solution containing sevoflurane plus orexin-B. Sevoflurane decreased the C4 burst rate and the integrated C4 amplitude. The C4 burst rate and amplitude were reversed by 0.5 μM orexin-B, but not by 0.1 μM orexin-B. The decrease induced in the C4 burst rate by 10 μM propofol or 0.01 μM remifentanil was significantly antagonized by 0.1 μM orexin-B. Respiratory depression induced by a higher concentration (0.1 μM) of remifentanil was not restored by 0.1 μM orexin-B. These results demonstrated that orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil.

Topics: Anesthetics; Animals; Animals, Newborn; Brain Stem; Disease Models, Animal; Intracellular Signaling Peptides and Proteins; Methyl Ethers; Neuropeptides; Orexins; Piperidines; Propofol; Rats; Rats, Wistar; Remifentanil; Respiratory Insufficiency; Sevoflurane; Spinal Cord

Management of difficult to wean patients is a dilemma for health care system. Recently published studies demonstrated efficacy of donepezil to counteract respiratory depression in sleep apnea. However, to the best of our knowledge, pharmaceutical interventions with donepezil to facilitate weaning have not been tested so far. Therefore in the present study, we evaluated the efficacy of using donepezil on weaning course in difficult to wean patients.. In this non-randomized interventional clinical study, difficult to wean patients with prior inappropriately depressed respiratory responses were included from two referral intensive care units (ICU) in Iran. Patients with another potentially reasons of weaning failure were excluded from the study. Donepezil was started for eligible patients at dose of 10 mg daily for 2-4 weeks. For the primary outcomes, arterial blood gas (ABG) parameters were also measured before and after intervention to evaluate the possible effects of donepezil on them. In addition, weaning outcomes of patients were reported as final outcome in response to this intervention.. Twelve out of 16 studied patients experienced successful results to facilitate weaning with donepezil intervention. The mean duration of donepezil treatment until outcome measurement was 12 days. There were not any significant differences in ABG parameters among patients with successful and failed weaning trial on day of donepezil initiation. However after donepezil intervention, mean of PCO2 and HCO3 decreased in patients with successful weaning trial and mean of PCO2 increased in those with weaning failure.. Reduced central respiratory drive was infrequently reason of failed weaning attempts but it must be considered especially in patients with hypercapnia secondary to inefficient gas exchange and slow breathing. Our results in the clinical setting suggest that, the use of donepezil can expedite weaning presumably by stimulation of respiratory center and obviate the need to re-intubation in cases of respiratory drive problem in difficult to wean patients. We suggest decrease PCO2 and HCO3 during donepezil steady could be valuable predictors for positive response to donepezil intervention.

Topics: Adult; Aged; Aged, 80 and over; Donepezil; Female; Humans; Indans; Male; Middle Aged; Pilot Projects; Piperidines; Respiratory Insufficiency; Treatment Outcome; Ventilator Weaning; Young Adult

Respiratory depression remains an important clinical problem that limits the use of opiate analgesia. Activation of AMPA glutamate receptors has been shown to reverse fentanyl-induced respiratory changes. Here, we explored whether tianeptine, a drug known for its ability to phosphorylate AMPA receptors, can be used to prevent opiate-induced respiratory depression. A model of respiratory depression in conscious rats was produced by administration of morphine (10mg/kg, i.p.). Rats were pre-treated with test compounds or control solutions 5min prior to administration of morphine. Respiratory activity was measured using whole-body plethysmography. In conscious animals, tianeptine (2 and 10mg/kg, ip) and DP-201 (2-(4-((3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2] thiazepin-11-yl)amino)butoxy)acetic acid; tianeptine analogue; 2mg/kg, ip) triggered significant (~30%) increases in baseline respiratory activity and prevented morphine-induced respiratory depression. These effects were similar to those produced by an ampakine CX-546 (15mg/kg, ip). The antinociceptive effect of morphine (hot plate test) was unaffected by tianeptine pre-treatment. In conclusion, the results of the experiments conducted in conscious rats demonstrate that systemic administration of tianeptine increases respiratory output and prevents morphine-induced respiratory depression without interfering with the antinociceptive effect of opiates.

Topics: Animals; Dioxanes; Dioxoles; Disease Models, Animal; Excitatory Amino Acid Agonists; Lung; Male; Morphine; Pain Threshold; Phosphorylation; Piperidines; Plethysmography, Whole Body; Rats, Sprague-Dawley; Receptors, AMPA; Respiration; Respiratory Insufficiency; Thiazepines; Time Factors

A 47-year-old woman with amyotrophic lateral sclerosis was scheduled for total thyroidectomy with cervical node dissection. During anesthetic management by total intravenous anesthesia using remifentanil, propofol, and rocuronium, train-of-four (TOF) monitoring findings were not consistent with clinical signs. Sugammadex successfully reversed shallow respiration.

Topics: Amyotrophic Lateral Sclerosis; Androstanols; Anesthesia, Intravenous; Anesthetics, Intravenous; Female; gamma-Cyclodextrins; Humans; Intraoperative Complications; Lymph Node Excision; Middle Aged; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Respiratory Insufficiency; Rocuronium; Sugammadex; Thyroidectomy

The pupillary light reflex is a critical component of the neurologic examination, yet whether it is present, depressed, or absent is unknown in patients with significant opioid toxicity. Although opioids produce miosis by activating the pupillary sphincter muscle, these agents may induce significant hypercarbia and hypoxia, causing pupillary constriction to be overcome via sympathetic activation. The presence of either "pinpoint pupils" or sympathetically mediated pupillary dilation might prevent light reflex assessment. This study was designed to determine whether the light reflex remains quantifiable during opioid-induced hypercarbia and hypoxia.. Ten volunteers were administered remifentanil with a gradually increasing infusion rate and intermittent boluses, until the increasing respiratory depression produced an oxyhemoglobin saturation of 85% or less with associated hypercarbia. Subjects' heart rate, blood pressure, respiration, and transcutaneous carbon dioxide level were continuously recorded. Arterial blood gases and pupillary measures were taken before opioid administration, at maximal desaturation, and 15 min after recovery.. The opioid-induced oxygen desaturation (≤ 85%) was associated with significant hypercarbia and evidence of sympathetic activation. During maximal hypoxia and hypercarbia, the pupil displayed parasympathetic dominance (2.5 ± 0.2 mm diameter) with a robust quantifiable light reflex. The reflex amplitude was linearly related to pupil diameter.. Opioid administration with significant accompanying hypercarbia and hypoxia results in pupil diameters of 2 to 3 mm and a reduced but quantifiable pupillary light reflex. The authors conclude that the pupillary examination and evaluation of the light reflex remain useful for neurologic assessment during opioid toxicity.

Topics: Adult; Analgesics, Opioid; Autonomic Nervous System; Blood Pressure; Carbon Dioxide; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Infusions, Intravenous; Male; Oxygen; Piperidines; Pupil; Reflex, Pupillary; Remifentanil; Respiratory Insufficiency

Ventilatory depression is a serious side-effect of opioid analgesics. Naloxone, an antagonist of opioid receptors, eliminates not only ventilatory depression but also analgesic effect of opioids. Pharmacological dissociation of adverse reactions from the main action is important clinically and basically. Cholinergic and serotonergic mechanisms are suggested to counteract the opioid-induced ventilatory disturbances, but their influence on analgesia is still controversial. The present study evaluated the effects of cholinesterase inhibitors and serotonin-1A (5-HT1A) receptor agonists on morphine (1.0mg/kg, i.v.)-induced ventilatory depression and analgesia in rats. In anesthetized animals, spontaneous ventilation and hind leg withdrawal reflexes against nociceptive thermal stimuli were measured simultaneously. Physostigmine (0.1 and 0.2mg/kg, i.v.) and donepezil (0.5 and 1.0mg/kg, i.v.) relieved the morphine-induced ventilatory depression and enhanced its antinociception. On the other hand, (±)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.03 and 0.1mg/kg, i.v.) and buspirone (0.1 and 0.3mg/kg, i.v.) did not influence antinociception of morphine while they restored the decreased ventilation. In unanesthetized animals, hypercapnic ventilatory response was measured by using whole-body plethysmography. Physostigmine (0.3mg/kg, i.p.), donepezil (1.0mg/kg, i.p.), 8-OH-DPAT (0.3mg/kg, i.p.) and buspirone (3.0mg/kg, i.p.) all recovered the morphine (10mg/kg, i.p.)-induced depression of hypercapnic ventilatory response. The present study suggests that activation of cholinergic or serotonergic (5-HT1A) mechanisms may be a useful therapeutic approach for morphine-induced ventilatory depression without loss of its analgesic action.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Analgesia; Animals; Buspirone; Cholinesterase Inhibitors; Donepezil; Indans; Male; Morphine; Pain; Physostigmine; Piperidines; Rats; Rats, Wistar; Respiratory Insufficiency; Serotonin 5-HT1 Receptor Agonists

Hyperoxaemia depresses the output of peripheral and central chemoreceptors. Patients treated with opioids often receive supplemental oxygen to avert possible decreases in oxygen saturation (Sp(O2)).We examined the effect of a single dose of remifentanil in healthy volunteers inhaling room air vs air enriched with 50% oxygen.. Twenty healthy volunteers received i.v. 50 mg remifentanil (infused over 60 s) at anormoxic (N) or hyperoxic (FI(O2) 0.5, H) background on separate occasions. Minute ventilation (Vi), respiratory rate (RR), end-tidal PC(O2), and Sp(O2) were collected on a breath to-breath basis. The occurrence of apnoea was recorded.. During normoxia, remifentanil decreased Vi from 7.4 (1.3) [mean (SD)] to 2.2 (1.2) litre min 21 (P,0.01), and during hyperoxia from 7.9 (1.0) to 1.2 (1.2) litre min 21 (P,0.01; H vs N: P,0.001). RR decreased from 13.1 (2.9) to 6.1 (2.8) bpm during N (P,0.01) and from 13.2 (3.0) to 3.6 (4.0) bpm during H (P,0.01; H vs N: P,0.01). During normoxia, Sp(O2) decreased from 98.4 (1.5) to 88.6 (6.7)% (P,0.01), while during hyperoxia, Sp(O2) changed from 99.7 (0.7) to 98.7 (1.0)% (P,0.001). Apnoea developed in two subjects during normoxia and 10 during hyperoxia.. Respiratory depression from remifentanil is more pronounced in hyperoxia than normoxia as determined from minute ventilation, end-tidal PC(O2), and RR. During hyperoxia, respiratory depression may be masked when measuring Sp(O2) as pulse oximetry remains in normal values during the first minutes of respiratory depression.

Topics: Adolescent; Adult; Analgesics, Opioid; False Negative Reactions; Female; Humans; Hyperoxia; Male; Monitoring, Physiologic; Oximetry; Oxygen; Oxygen Inhalation Therapy; Piperidines; Remifentanil; Respiratory Insufficiency; Respiratory Rate; Young Adult

5-HT(1A)-R-agonist repinotan was shown to counteract a morphine-induced ventilatory depression but had pronociceptive effects at small doses (0.2 μg/kg). It remained to be clarified (1) whether a moderate dose of repinotan, sufficient to stimulate spontaneous breathing, impairs antinociception if plasma concentration decreases over time, and if (2) moderate doses prevent ventilatory depression if given before the opioid.. A dose-response curve of the repinotan effects on spontaneous minute ventilation during continuous remifentanil infusion in anesthetized rats was established to identify moderate doses: (1) tail-flick reflex latencies to assess nociception were recorded until 60 min after cessation of a continuous remifentanil infusion with or without a concomitant moderate repinotan dose (10 μg/kg), and (2) remifentanil boluses (2.5 μg/kg) were given after repinotan (10 and 20 μg/kg).. (1) Remifentanil-induced antinociception lasted only 5 min after infusion was stopped (tail-flick reflex latencies; median [interquartile range], 97 [54-100]% of maximum possible effect; P = 0.034), but was extended by repinotan (10 μg/kg) to 30 min (tail-flick reflex latencies, 100 [75-100]% of maximum possible effect; P = 0.031). Repinotan (10 μg/kg) alone did not have any significant antinociceptive effect. (2) The ventilatory depression by remifentanil boluses (2.5 μg/kg; minute ventilation, -65 [-81 to -56]%; P = 0.031, n = 5) was blunted by repinotan (20 μg/kg; minute ventilation, -24 [-53 to 13]%; P = 0.313, compared with the pretreatment level).. Repinotan prevented remifentanil-induced ventilatory depression in spontaneously breathing, anesthetized rats. Although repinotan did not depress nociception itself, it prolonged the profound antinociception after discontinuation of remifentanil infusion.

Topics: Analgesics, Opioid; Anesthetics, Intravenous; Animals; Benzopyrans; Blood Pressure; Dose-Response Relationship, Drug; Heart Rate; Hemodynamics; Hypnotics and Sedatives; Male; Pain Measurement; Piperidines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Remifentanil; Respiratory Insufficiency; Respiratory Mechanics; Serotonin Receptor Agonists; Thiazoles

Remifentanil patient-controlled analgesia is well established in many centres and provides satisfactory pain relief for many women in labour. We describe a patient using remifentanil patient-controlled analgesia who suffered a respiratory arrest requiring a brief period of ventilation. In our institution, remifentanil patient-controlled analgesia has been offered to women in labour since 2009. Up to this point, we had not observed any critical incidents in over 130 patients using this mode of analgesia in our labour suite.

Topics: Adolescent; Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Labor, Obstetric; Oxygen Inhalation Therapy; Piperidines; Pregnancy; Pregnancy Complications; Remifentanil; Respiratory Insufficiency

Topics: Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Piperidines; Pregnancy; Pregnancy Complications; Respiratory Insufficiency

Topics: Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Piperidines; Pregnancy; Pregnancy Complications; Respiratory Insufficiency

Topics: Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Piperidines; Pregnancy; Pregnancy Complications; Respiratory Insufficiency

Topics: Analgesia, Obstetrical; Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Humans; Piperidines; Pregnancy; Pregnancy Complications; Respiratory Insufficiency

Topics: Anesthetics, Combined; Anesthetics, Intravenous; Esophagus; Female; Humans; Male; Piperidines; Propofol; Remifentanil; Respiratory Insufficiency; Sensation

Cholinesterase inhibitors (ChEIs) may interact with muscle relaxants given during general anesthesia (GA), increasing the risk of postoperative complications. We evaluated the effects of ChEIs on the postoperative outcomes of older adults who underwent hip fracture surgery.. Population-based cohort study using linked administrative databases.. All individuals with dementia age 66 years or older, who underwent hip fracture surgery between April 1, 2003, and December 31, 2007, in Ontario, Canada.. Use of any ChEI (donepezil, rivastigmine, or galantamine) before surgery.. The primary composite outcome included any of the following: 30-day postoperative mortality; intensive care unit admissions; or in-hospital resuscitation. Secondary outcomes included postoperative respiratory failure and pneumonia.. We stratified the study sample on the basis of residence (community or long-term care [LTC]) and type of anesthetic (general or regional) to create four residence/anesthesia groups. We used propensity scores to match users and nonusers of ChEIs within the residence/anesthesia strata. We then calculated the relative risks (RR) and 95% confidence intervals (CI) for outcomes associated with ChEIs in the matched groups.. A total of 624 pairs of individuals from the community and 725 pairs from LTC were created among individuals who received GA. High rates of postoperative mortality and complications were observed in both ChEI users and nonusers. The RR of the primary outcome associated with ChEI use for individuals receiving GA was 0.88 (95% CI: 0.68-1.16; χ2 = 0.93; df = 1; p = 0.34) and 0.82 (95% CI: 0.63-1.04; χ2 = 2.59; df = 1; p = 0.11) in the community and LTC groups, respectively. In addition, ChEIs were not associated with any significant increased risk of postoperative respiratory complications.. ChEI use was not associated with an increased risk of postoperative complications among older adults with dementia who underwent hip fracture surgery. However, the poor postoperative outcomes overall reinforced the need to prevent fractures and improve outcomes in this population.

Topics: Aged; Aged, 80 and over; Anesthesia, General; Cholinesterase Inhibitors; Cohort Studies; Critical Care; Dementia; Donepezil; Female; Galantamine; Hip Fractures; Humans; Indans; Male; Outcome and Process Assessment, Health Care; Phenylcarbamates; Piperidines; Pneumonia; Postoperative Complications; Respiratory Insufficiency; Resuscitation; Risk; Rivastigmine

Topics: Adult; Anesthetics, Intravenous; Humans; Male; Piperidines; Remifentanil; Respiratory Insufficiency; Time Factors

This study compares basic respiratory variables (rate, tidal and minute volumes) with time-, flow- and ratio-derived parameters obtained using head-out plethysmography in rats following administration of reference drugs (isotonic saline, 2.0 mL/kg, IV; albuterol, 400 μg/kg, inhalation; methacholine, 136 μg/kg, IV; and remifentanil, 14 μg/kg, IV) to identify respiratory variables with superior sensitivity. Paired t-tests by block-period, and analysis of covariance (ANCOVA) with baseline as covariate and a posteriori pair-wise comparisons using Dunnett's test were used. Variations in respiratory parameters observed over time justify the use of a control group in any respiratory safety pharmacology study for inter-groups comparison. Handling-, and slumbering-, induced perturbations were minimal. The system was sensitive and specific to detect changes in respiratory variables related to pharmacologically-induced bronchodilation, bronchoconstriction and central respiratory depression. The standard variables (respiratory rate, tidal and minute volumes) confirmed to be the cornerstone of respiratory safety pharmacology to detect pharmacological changes. Flow-derived parameters appeared as highly valuable complement for interpretation of respiratory response, whereas time- and ratio-derived parameters presented limited added value during interpretation.

Topics: Albuterol; Animals; Bronchoconstriction; Consciousness; Dose-Response Relationship, Drug; Inspiratory Capacity; Male; Methacholine Chloride; Piperidines; Plethysmography; Rats; Rats, Sprague-Dawley; Remifentanil; Reproducibility of Results; Respiration; Respiratory Function Tests; Respiratory Insufficiency; Respiratory Rate; Respiratory System; Sodium Chloride; Tidal Volume

To investigate the respiratory, metabolic and hemodynamic effects of clonidine in ventilated patients presenting with withdrawal syndrome after sedation interruption.. Prospective, interventional, single-center study in 30 ventilated ICU patients.. Metabolic [oxygen consumption (VO(2)), CO(2) production (VCO(2)), resting energy expenditure (REE)], respiratory [minute ventilation (V (E)), tidal volume (V (T)), respiratory rate (RR)] and hemodynamic (HR, SAP, MAP) parameters were measured in 30 ventilated ICU patients. Measurements were performed first under sedation with remifentanil-propofol, then after sedation interruption, and finally after clonidine administration (0.9-1.8 mg of clonidine in two doses of 10 min interval).. Sedation interruption produced significant increases in the hemodynamic parameters (SAP and MAP by 33%, HR by 37%), and metabolic rate (increase in VO(2) by 70%, VCO(2) by 88% and REE by 74%), leading to high respiratory demands (increase in V (E) from 9 to 15 l/min). The V (E) was increased due to a twofold increase in the RR; V (T) remained constant. In 25 out of 30 patients, clonidine administration decreased the hemodynamic (SAP, MAP and HR), metabolic (VO(2), VCO(2), REE) and respiratory parameters to values close to those observed with sedation. Clonidine induced mild sedation and patients became more cooperative with the ventilator. All patients responding to clonidine were weaned from the ventilator in 2 days (median, range 1-18 days).. Patients with withdrawal syndrome had significantly elevated hemodynamic, metabolic and respiratory demands. Clonidine significantly decreased these demands, induced mild sedation and facilitated patient cooperation with the ventilator, enabling ventilator weaning.

Topics: Adrenergic alpha-Agonists; Adult; Calorimetry, Indirect; Carbon Dioxide; Clonidine; Electrocardiography; Energy Metabolism; Female; Hemodynamics; Humans; Hypertension; Hypnotics and Sedatives; Male; Oxygen Consumption; Piperidines; Propofol; Prospective Studies; Remifentanil; Respiration, Artificial; Respiratory Insufficiency; Rest; Substance Withdrawal Syndrome; Tachycardia; Ventilator Weaning

Topics: Conscious Sedation; Fiber Optic Technology; Humans; Hypnotics and Sedatives; Intubation, Intratracheal; Piperidines; Remifentanil; Respiratory Insufficiency

Behavioral effects of a nonpeptidic NOP (nociceptin/orphanin FQ Peptide) receptor agonist, Ro 64-6198, have not been studied in primate species. The aim of the study was to verify the receptor mechanism underlying the behavioral effects of Ro 64-6198 and to systematically compare behavioral effects of Ro 64-6198 with those of a mu-opioid receptor agonist, alfentanil, in monkeys. Both Ro 64-6198 (0.001-0.06 mg/kg, s.c.) and alfentanil (0.001-0.06 mg/kg, s.c.) produced antinociception against an acute noxious stimulus (50 degrees C water) and capsaicin-induced allodynia. An NOP receptor antagonist, J-113397 (0.01-0.1 mg/kg, s.c.), dose-dependently produced rightward shifts of the dose-response curve of Ro 64-6198-induced antinociception. The apparent pA(2) value of J-113397 was 8.0. Antagonist studies using J-113397 and naltrexone revealed that Ro 64-6198 produced NOP receptor-mediated antinociception independent of mu-opioid receptors. In addition, alfentanil dose-dependently produced respiratory depression and itch/scratching responses, but antinociceptive doses of Ro 64-6198 did not produce such effects. More important, Ro 64-6198 did not produce reinforcing effects comparable with those of alfentanil, cocaine, or methohexital under self-administration procedures in monkeys. These results provide the first functional evidence that the activation of NOP receptors produces antinociception without reinforcing effects in primates. Non-peptidic NOP receptor agonists may have therapeutic value as novel analgesics without abuse liability in humans.

Topics: Alfentanil; Analgesics, Opioid; Animals; Behavior, Animal; Benzimidazoles; Capsaicin; Central Nervous System Agents; Dose-Response Relationship, Drug; Female; Hot Temperature; Imidazoles; Macaca mulatta; Male; Naltrexone; Narcotic Antagonists; Nociceptin Receptor; Pain; Piperidines; Pruritus; Receptors, Opioid; Receptors, Opioid, mu; Reinforcement, Psychology; Respiratory Insufficiency; Spiro Compounds

To assess efficacy of remifentanil in preterm newborns during mechanical ventilation.. Remifentanil was administered by continuous intravenous infusion to provide analgesia and sedation in 48 preterm infants who developed respiratory distress and required mechanical ventilation. We examined the doses needed to provide adequate analgesia, extubation time after the discontinuation of opioid infusion, the presence of side effects and safety of the use.. Remifentanil provided adequate analgesia, with a significant reduction of NIPS and COMFORT score since 1 h after starting the infusion of remifentanil. The drug was initially administered at a dose of 0.075 microg/kg/min, but in 73% of newborns the latter had to be increased; at a dose of 0.094 +/- 0.03 (mean +/- standard deviation) microg/kg/min, 97% of the newborns received adequate analgesia and sedation. The time elapsed between the discontinuation of remifentanil infusion and extubation was 36 +/- 12 min. Treatment was started between the 1st and the 17th day of life. The mean duration of therapy was 5.9 +/- 5.7 days. No side effects on the respiratory or cardiovascular system were observed.. Remifentanil is a manageable and effective opioid in the newborn undergoing mechanical ventilation, though randomized controlled trials and information about long-term outcomes are necessary.

Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Multivariate Analysis; Pain Measurement; Piperidines; Pneumonia; Remifentanil; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Respiratory Mechanics

Rats are most frequently used to fulfill ICH S7A requirements for respiratory safety pharmacology. We hypothesized that the models used to assess respiratory safety pharmacology present different ventilatory responses to bronchoconstriction, bronchodilation and respiratory depression. Respiratory monitoring was performed with head-out plethysmographs for rats, masks for dogs and bias airflow helmets for monkeys. Respiratory rate (RR), tidal volume (TV) and minute volume (MV) were recorded. Forty rats, 18 dogs and 8 monkeys were acclimated to the respiratory monitoring equipment. Animals received saline (IV), albuterol (inhalation), methacholine (IV) and remifentanil (IV). Albuterol increased TV in all species. Methacholine decreased TV and MV in monkeys. In dogs, methacholine increased TV, RR and MV. In rats, methacholine increased TV and decreased RR. Remifentanil induced central respiratory depression in all species with decreased MV, except in rats. Dogs presented a biphasic response to remifentanil with hypoventilation followed by delayed hyperventilation. The monkeys presented similar responses to humans which may be due to biologic similarities. Dogs and rats presented clinically significant ventilatory alterations following positive control drugs. Although, the response to bronchoconstriction in dogs and rats was different from humans, the two species presented ventilatory changes that highlight the potential adverse effect of test articles.

Topics: Albuterol; Animals; Bronchoconstrictor Agents; Bronchodilator Agents; Dogs; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hyperventilation; Hypoventilation; Macaca fascicularis; Male; Methacholine Chloride; Pharmaceutical Preparations; Piperidines; Rats; Remifentanil; Respiration; Respiratory Function Tests; Respiratory Insufficiency; Species Specificity

We report that spontaneous breathing under total intravenous anesthesia by 0.1 microg x kg(-1) x hr(-1) of remifentanil and 3 mg x kg(-1) x hr(-1) of propoforl can be maintained during the surgery for tracheobronchial stent insertion in a man with severe trachea stenosis. Remifentanil is an ultra-short acting narcotic, and is excellent for relieving pain maintaining stable hemodynamics. As this drug is used at a low dose, it is suitable for this case which requires a short time of operation, minimally invasive surgery, prevention of moving, and the spontaneous breathing. We could achieve steady respiratory and hemodynamic control.

Topics: Aged; Anesthesia, Intravenous; Bronchoscopes; Humans; Male; Piperidines; Propofol; Remifentanil; Respiration; Respiratory Insufficiency; Severity of Illness Index; Stents; Tracheal Stenosis

Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and chronic pain management. Although this agent's analgesic effect increases in a dose-dependent manner, buprenorphine-induced respiratory depression shows a marked ceiling effect at higher doses, which is considered to be an indicator of safety. Nevertheless, cases of overdose mortality or severe respiratory depression associated with buprenorphine use have been reported. Naloxone can reverse buprenorphine-induced respiratory depression, but is slow-acting and unstable, meaning that new drug candidates able to specifically antagonize buprenorphine-induced respiratory depression are needed in order to enable maximal analgesic effect without respiratory depression. Acetylcholine is an excitatory neurotransmitter in central respiratory control. We previously showed that a long-acting acetylcholinesterase inhibitor, donepezil, antagonizes morphine-induced respiratory depression. We have now investigated how donepezil affects buprenorphine-induced respiratory depression in anesthetized, paralyzed, and artificially ventilated rabbits. We measured phrenic nerve discharge as an Index of respiratory rate and amplitude, and compared discharges following the injection of buprenorphine with discharges following the injection of donepezil. Buprenorphine-induced suppression of the respiratory rate and respiratory amplitude was antagonized by donepezil (78.4 +/- 4.8 %, 92.3% +/- 22.8 % of control, respectively). These findings indicate that systemically administered donepezil restores buprenorphine-induced respiratory depression in anesthetized rabbits.

Topics: Animals; Buprenorphine; Cholinesterase Inhibitors; Donepezil; Indans; Male; Narcotic Antagonists; Phrenic Nerve; Piperidines; Rabbits; Respiratory Insufficiency

To assess the feasibility and safety of remifentanil-based sedation during noninvasive ventilation (NIV) in patients with NIV failure.. Prospective clinical investigation in a 16-bed intensive care unit of a university hospital in France.. Thirteen patients in NIV failure due to discomfort and/or refusal to continue this ventilatory support: 10 with acute respiratory failure and 3 with acute hypercapnic respiratory failure.. Patients were administered methylene blue and were sedated (Ramsay scale 2-3) by a continuous perfusion of remifentanil during NIV. Cardiorespiratory and ventilatory parameters, blood gas analysis, and adverse events were prospectively recorded.. The 13 patients received a total of 125 NIV sessions, totaling 1200 h, of NIV under remifentanil-based sedation (mean remifentanil dose 0.1+/-0.03 microg/kg per minute). Three patients also required propofol. PaO2/FIO2 ratio increased from 134+/-69 to 187+/-43 mmHg after 1 h. In patients with acute respiratory failure respiratory rate decreased from 34+/-12 per minute before remifentanil to 25+/-4 per minute after 1h. In the three patients with acute hypercapnic respiratory failure PaCO2 decreased from 69+/-7 to 42+/-5 mmHg. Four patients required endotracheal intubation without aspiration pneumonia. Twelve of the 13 patients left the ICU.. This pilot study shows that remifentanil-based sedation is safe and effective in the treatment of NIV failure due to low tolerance.

Topics: Adult; Aged; Aged, 80 and over; Conscious Sedation; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperidines; Prospective Studies; Remifentanil; Respiration, Artificial; Respiratory Insufficiency; Treatment Failure

Topics: Anesthesia, Epidural; Anesthetics, Combined; Anesthetics, Intravenous; Anesthetics, Local; Cholecystectomy; Epinephrine; Humans; Injections, Epidural; Laryngeal Masks; Lidocaine; Male; Medication Errors; Middle Aged; Piperidines; Remifentanil; Respiration, Artificial; Respiratory Insufficiency

Anesthesia for patients with Steinert's syndrome (myotonic dystrophy, MD) is a challenge for the anaesthetist. MD is a multisystemic disease and the neuromuscular symptoms can be associated with sleep apnea, endocrine disorders (diabetes, hypogonadism, hypothyroidism), cardiac, gastroenteric or cognitive disorders (mental deficiency, attention disorders). The diagnosis is facilitated when one or more of these symptoms are associated with the neuromuscular symptoms; however, the latter are not always present at the onset, which makes the diagnosis of MD a difficult and often late one. The choice of drugs and the choice of anesthesia in these patients can be very challenging for many reasons. A myotonic crisis can be triggered by several factors including hypothermia, shivering and mechanical or electrical stimulation. These patients are very sensitive to the usual anesthetics such as hypnotics and paralyzing agents (both depolarizing and nondepolarizing). The following case report describes pathophysiological considerations and a technique for anaesthesia during thoracic surgery that has been able to assure hemodynamic peroperative stability, early extubation and prolonged respiratory autonomy in a patient affected by this genetic disorder.

Topics: Aged; Anesthesia, Intravenous; Anesthetics, Intravenous; Atracurium; Humans; Male; Myotonic Dystrophy; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Respiratory Insufficiency; Thoracotomy

There is a need for improved therapeutic interventions to treat both drug- and sleep-induced respiratory depression. Increased understanding of the neurochemical control of respiration will help identify a basis for advances. Activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors positively modulates respiratory drive and rhythmogenesis in several brain regions including the pre-Bötzinger complex. Ampakines are a diverse group of small molecules that activate subsets of these receptors.. We determined whether the ampakine CX546 would enhance respiratory drive and rhythmogenesis across various stages of development and whether this ampakine could counter opioid- and barbiturate-induced respiratory depression.. Respiratory frequency and amplitude were measured in the following rat models: (1) perinatal in vitro brainstem-spinal cord, (2) neonatal in vitro medullary slice, (3) juvenile in situ perfused, working heart-brainstem preparation, and (4) newborn and adult in vivo.. Administration of CX546 stimulated baseline respiratory frequency in perinatal in vitro preparations but not in older animals (greater than Postnatal Day 0). Furthermore, pharmacologic depression of respiratory frequency and amplitude was countered at all ages studied by the administration of CX546 in vitro, in situ, and in vivo. Significantly, CX546 countered opioid-induced breathing depression in all preparations, without altering analgesia as assessed by measuring the time to foot withdrawal in response to a thermal stimulus.. CX546 effectively reverses opioid- and barbiturate-induced respiratory depression without reversing the analgesic response. These studies suggest that ampakines may be useful in preventing or reversing opioid-induced respiratory depression and identify the potential of ampakines for alleviating other forms of respiratory depression including sedative use and sleep apnea.

Topics: Analgesics, Opioid; Animals; Animals, Newborn; Barbiturates; Dioxoles; In Vitro Techniques; Pain Measurement; Piperidines; Plethysmography; Rats; Rats, Sprague-Dawley; Respiration; Respiratory Insufficiency

Topics: Analgesics, Opioid; Anesthetics, Intravenous; Humans; Injections, Intravenous; Piperidines; Remifentanil; Respiratory Insufficiency

Remifentanil is a useful adjunct in general anesthesia for high-risk obstetric patients. It provides effective blunting of the rapid hemodynamic changes that may be associated with airway manipulation and surgical stimulation. There have been no previous reports of opioid-related rigidity in the neonate delivered by a parturient receiving intraoperative remifentanil. We present a case of short-lived neonatal rigidity and respiratory depression following remifentanil administration during cesarean section to a parturient with autoimmune hepatitis complicated by cirrhosis, esophageal varices and thrombocytopenia.

Topics: Adult; Analgesia, Obstetrical; Analgesics, Opioid; Blood Pressure; Cesarean Section; Esophageal and Gastric Varices; Female; Heart Rate; Hepatitis, Autoimmune; Humans; Infant, Newborn; Male; Muscle Rigidity; Piperidines; Pregnancy; Remifentanil; Respiratory Insufficiency; Thoracic Wall; Thrombocytopenia

During opioid administration, decreasing respiratory rate is typically used as a predictor of respiratory depression. Prior to opioid-induced apnea, progressively irregular breathing patterns have been noticed. We hypothesize that opioid administration to children will increase tidal volume variability (TV(var)) and that this will be a better predictor of respiratory depression than a decrease in respiratory rate.. We recruited 32 children aged 2-8 years scheduled to undergo surgery. During spontaneous ventilation, flow rates and respiratory rates were continuously recorded, while remifentanil was infused at stepwise increasing doses each lasting 10 min. The infusion was continued until the patient showed signs of respiratory depression. Flow data from each dose was used to calculate tidal volumes, from which TV(var) was calculated. The respiratory rate and TV(var) during the last (D(last)), second to last (D-2), and third to last (D-3), administered doses were compared to those during baseline (fourth to last dose). We chose a threshold of TV(var) increase and compared it to a decrease in respiratory rate below 10 breaths per min as predictors of respiratory depression.. Compared to baseline, the TV(var) increased by 336% and 668% during D(-2) and D(last), respectively, whereas respiratory rate decreased by 14.3%, 31.7%, and 55.5% during D(-3), D(-2), and D(last), respectively. A threshold increase in TV(var) of 150% over baseline correctly predicted respiratory depression in 41% of patients, compared to a drop in respiratory rate correctly predicting 22% of patients.. TV(var) increases as children approach opioid-induced respiratory depression. This is a more useful predictor of respiratory depression than a fall in respiratory rate because the TV(var) increase is 10 times the drop in respiratory rate. A TV(var) increase also correctly predicts respiratory depression twice as often as decreased respiratory rate and is independent of age-related alterations in physiologic respiratory rates.

Topics: Analgesics, Opioid; Anesthetics, Intravenous; Body Size; Child; Child, Preschool; Female; Humans; Male; Piperidines; Remifentanil; Respiration; Respiratory Insufficiency; Tidal Volume

The C50 of remifentanil for ventilatory depression has been previously determined using inspired carbon dioxide and stimulated ventilation, which may not describe the clinically relevant situation in which ventilatory depression occurs in the absence of inspired carbon dioxide. The authors applied indirect effect modeling to non-steady state Paco2 data in the absence of inspired carbon dioxide during and after administration of remifentanil.. Ten volunteers underwent determination of carbon dioxide responsiveness using a rebreathing design, and a model was fit to the end-expiratory carbon dioxide and minute ventilation. Afterwards, the volunteers received remifentanil in a stepwise ascending pattern using a computer-controlled infusion pump until significant ventilatory depression occurred (end-tidal carbon dioxide [Peco2] > 65 mmHg and/or imminent apnea). Thereafter, the concentration was reduced to 1 ng/ml. Remifentanil pharmacokinetics and Paco2 were determined from frequent arterial blood samples. An indirect response model was used to describe the Paco2 time course as a function of remifentanil concentration.. The time course of hypercarbia after administration of remifentanil was well described by the following pharmacodynamic parameters: F (gain of the carbon dioxide response), 4.30; ke0 carbon dioxide, 0.92 min-1; baseline Paco2, 42.4 mmHg; baseline minute ventilation, 7.06 l/min; kel,CO2, 0.08 min-1; C50 for ventilatory depression, 0.92 ng/ml; Hill coefficient, 1.25.. Remifentanil is a potent ventilatory depressant. Simulations demonstrated that remifentanil concentrations well tolerated in the steady state will cause a clinically significant hypoventilation following bolus administration, confirming the acute risk of bolus administration of fast-acting opioids in spontaneously breathing patients.

Topics: Adult; Bayes Theorem; Confidence Intervals; Dose-Response Relationship, Drug; Female; Humans; Linear Models; Male; Models, Biological; Piperidines; Pulmonary Ventilation; Remifentanil; Respiratory Insufficiency

During this investigation, which involved 58 Belgian White and Blue double-muscled calves affected by a naturally occurring Acute Respiratory Distress Syndrome, the clinical efficiency of a 5-HT2 receptor blockade with metrenperone (group A) was compared to the efficiency of a non-steroidal (flunixine meglumine--group B) and a steroidal (prednisolone sodium succinate--group C) antiinflammatory drug. Each animal of this trial was treated with ceftiofur sodium as antimicrobial agent. A clinical score and a breathing score were calculated at each step of the investigation period, i.e. before (T0) and 1 hour (T1), 12 hours (H), 24 H, 48H and 168 H (T3) after the first treatment, the interval 12H-48H being considered as period T2. Three clinical parameters were also taken into account separately: rectal and peripheral temperatures and heart rate. A significant improvement of the clinical score was registered at T2 in group A and at T3 in groups A and B, while this score did not significantly change in group C. In group A, the breathing score was significantly improved at T2 and T3, but not in groups B and C. Peripheral and rectal temperatures recorded at T1 were, in group A, significantly increased and decreased respectively, but not significantly changed in groups B and C. The proportions requiring change of treatment during the investigation period were significantly (P = 0.022) different in the three groups, being 5.6, 21.4 and 50.0% in groups A, B and C respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cattle; Cattle Diseases; Piperidines; Respiratory Insufficiency; Serotonin Antagonists; Syndrome

Topics: Adolescent; Adult; Aged; Dexetimide; Humans; Middle Aged; Muscular Diseases; Myasthenia Gravis; Parasympathomimetics; Piperidines; Respiratory Insufficiency

An early event in the evolution of acute respiratory failure (ARF) is thought to be the activation of platelets, their pulmonary entrapment and subsequent release of the smooth muscle constrictor serotonin (5HT). This study tests the thesis that inhibition of 5HT will improve lung function. The etiology of ARF in the 18 study patients was sepsis (N = 10), aspiration (N = 3), pancreatitis (N = 1), embolism (N = 2), and abdominal aortic aneurysm surgery (N = 2). Patients were divided into two groups determined by whether their period of endotracheal intubation was less than or equal to 4 days (early ARF, N = 12) or greater than 4 days (late ARF, N = 6). Transpulmonary platelet counts in the early group showed entrapment of 26,300 +/- 5900 platelets/mm3 in contrast to the late group where there was no entrapment (p less than 0.05). The platelet 5HT levels in the early group were 55 +/- 5 ng/10(9) platelets, values lower than 95 +/- 15 ng/10(9) platelets in the late ARF group (p less than 0.05), and 290 +/- 70 ng/10(9) platelets in normals. The selective 5HT receptor antagonist, ketanserin was given as an intravenous bolus over 3 minutes in a dose of 0.1 mg/kg, followed by a 30-minute infusion of 0.08 mg/kg. During this period mean arterial pressure (MAP) fell from 87 +/- 5 to 74 +/- 6 mmHg (mean +/- SEM) (p less than 0.05). One and one-half hours following the start of therapy, MAP returned to baseline. At this time, patients with early ARF showed decreases in: physiologic shunt (Qs/QT) from 26 +/- 3 to 19 +/- 3 (p less than 0.05); peak inspiratory pressure from 35 +/- 2 to 32 +/- 2 cmH2O (p less than 0.05) and in mean pulmonary arterial pressure from 32 +/- 2 to 29 +/- 1 mmHg (p less than 0.05). At 4 hours all changes returned to baseline levels. In early ARF ketanserin did not alter pretreatment values of: pulmonary arterial wedge pressure, 17 +/- 3 mmHg; cardiac index, 2.8 +/- 0.3 L/min X m2; platelet count, 219,000 +/- 45,000/mm3; platelet 5HT, 55 +/- 5 ng/10(9) platelets; plasma 5HT, 142 +/- 21 ng/ml; plasma thromboxane B2, 190 +/- 30 pg/ml; or plasma 6-keto-PGF1 alpha, 40 +/- 10 pg/ml. Ketanserin infusion in patients with late ARF yielded no benefit. In both ARF groups the decreases in QS/QT were inversely related to the duration of intubation (r = 0.70; p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Aged; Blood Platelets; Blood Pressure; Cardiac Output; Female; Humans; Intubation, Intratracheal; Ketanserin; Male; Middle Aged; Piperidines; Platelet Count; Pulmonary Wedge Pressure; Respiratory Function Tests; Respiratory Insufficiency; Serotonin; Serotonin Antagonists; Thromboxane B2

Increased release of serotonin (5-hydroxytryptamine, 5-HT) can play a significant role in the development of acute respiratory failure. The hemodynamic effects of ketanserin, a selective inhibitor of 5-HT2 receptors, were studied in eight patients who developed acute respiratory insufficiency after an episode of circulatory shock. Administration of ketanserin was associated with reductions in systemic and pulmonary artery pressures, without significant change in heart rate or cardiac output. Concomitant decreases in hemoglobin and protein concentrations suggested an associated increase in plasma volume. These changes were attributed to an increased peripheral pooling of blood related to vasodilation. Arterial oxygenation and pulmonary shunt were unaffected. These results indicate ketanserin represents a promising vasoactive agent for treatment of acute respiratory failure in critically ill patients.

Topics: Adult; Aged; Blood Proteins; Erythrocyte Indices; Female; Humans; Ketanserin; Male; Middle Aged; Piperidines; Pulmonary Wedge Pressure; Respiratory Insufficiency; Stroke Volume; Vascular Resistance

Topics: Acidosis, Respiratory; Acute Disease; Adult; Aged; Alkalosis, Respiratory; Aminophylline; Anti-Bacterial Agents; Chronic Disease; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Oxygen Inhalation Therapy; Partial Pressure; Piperidines; Prednisone; Prognosis; Respiratory Insufficiency; Spirometry

Topics: Adjuvants, Anesthesia; Adolescent; Adult; Aged; Androstanes; Animals; Bromides; Dogs; Drug Synergism; Electromyography; Female; Humans; Male; Middle Aged; Neostigmine; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Pancuronium; Piperidines; Respiratory Insufficiency; Succinylcholine; Thiamine

Topics: Acetazolamide; Amides; Chronic Disease; Clopamide; Diuretics; Humans; Hydrogen-Ion Concentration; Lung Diseases; Piperidines; Respiratory Insufficiency

Topics: Acetazolamide; Acid-Base Equilibrium; Acidosis, Respiratory; Amides; Bronchial Diseases; Clopamide; Diuretics; Ethacrynic Acid; Humans; Hypercapnia; Lung Diseases; Piperidines; Respiratory Insufficiency

Topics: Adult; Aminophylline; Cough; Dyspnea; Female; Humans; Isoproterenol; Male; Middle Aged; Piperidines; Pulmonary Emphysema; Respiratory Function Tests; Respiratory Insufficiency; Respiratory System; Sputum

Topics: Anti-Allergic Agents; Asthma; Bronchitis; Drug Therapy; Histamine H1 Antagonists; Piperidines; Respiratory Insufficiency; Thioxanthenes