piperidines and Hypercapnia

We studied the impact of transcutaneous continuous carbon dioxide tension (PtcCO2) monitoring on ventilation and oxygenation during monitored anaesthesia care (MAC) in patients scheduled for shoulder surgery with continuous interscalene block. 50 patients were randomised either to the intervention (I-group) or the control (C-group) group. In both groups MAC was performed using target controlled infusion of propofol and remifentanil. MAC regimen was adapted to PtcCO2 values in the I-group, whereas the C-group was blinded for these values. Primary outcome was the incidence, degree and duration of hypoventilation stages. In the I-group and the C-group the mean ± SD [range] of PtcCO2 and PaCO2 was 5.79 ± 0.84 [4.37] and 5.44 ± 0.59 [2.78] kPa, as well as 6.41 ± 1.17 [6.29] and 6.01 ± 0.96 [7.15] kPa. Periods of PtcCO2/PaCO2 > 6.5 kPa were 21.0 ± 35.7/1.2 ± 4.2 min in the I-group and 45.6 ± 40.0/18.6 ± 26.8 min in the C-group. Severe hypercapnia (PtcCO2 and/or PaCO2 > 7.5 kPa) was dected in 3/0 patients of the I-group and in 10/3 patients of the C-group. PtcCO2 and PaCO2 showed a strong correlation (r = 0.78), but only moderate agreement with a mean bias (LOA) of -0.37 (-1.69; +0.95) kPa showing an overestimation of the PaCO2. Sensitivity and specificity of PtcCO2 to detect changes of PaCO2 was 0.94 and 0.56, respectively. In no patient SpO2 or SaO2 values lower than 90% were measured. Despite a moderate agreement between PaCO2 and PtcCO2 the PtcCO2 monitoring significantly reduced incidence, degree and duration of hypercapnia in shoulder surgery patients with MAC.

Topics: Adult; Anesthesia, Conduction; Anesthetics, Intravenous; Blood Gas Monitoring, Transcutaneous; Carbon Dioxide; Female; Humans; Hypercapnia; Incidence; Male; Middle Aged; Monitoring, Intraoperative; Monitoring, Physiologic; Oxygen; Piperidines; Propofol; Prospective Studies; Remifentanil; Reproducibility of Results; Sensitivity and Specificity; Shoulder

Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients, has minimal effect on ventilation.. This study compared the respiratory effect of dexmedetomidine to that of remifentanil. The authors measured and compared respiratory responses of six healthy male volunteers during (1) a stepwise target-controlled infusion of remifentanil, (2) a stepwise target-controlled infusion of dexmedetomidine, and (3) a pseudonatural sleep session.. Compared with baseline, remifentanil infusions resulted in respiratory depression as evidenced by a decrease in respiratory rate and minute ventilation, respiratory acidosis, and apnea episodes resulting in desaturations. Remifentanil disturbed the natural pattern of breathing and flattened the distribution of ventilatory timing (inspiratory time/ventilatory cycle time). The respiratory effects of dexmedetomidine markedly contrasted with those of remifentanil. When compared with baseline, during dexmedetomidine infusions, the respiratory rate significantly increased, and the overall apnea/hypopnea index significantly decreased. The distribution of inspiratory time/ventilatory cycle time showed an increased peak. In addition, dexmedetomidine seemed to mimic some aspect of natural sleep. While the subjects were breathing a 5% CO2 mixture, hypercapnic arousal phenomena (documented by the Bispectral Index, the electroencephalogram, and sudden increase in the minute ventilation) were observed during dexmedetomidine infusions. Similar phenomena during natural sleep have been reported in the literature.. In comparison with remifentanil, dexmedetomidine infusions (1) did not result in clinically significant respiratory depression, (2) decreased rather than increased the apnea/hypopnea index, and (3) exhibited some similarity with natural sleep.

Topics: Adult; Algorithms; Analgesics, Opioid; Calibration; Carbon Dioxide; Cross-Over Studies; Dexmedetomidine; Electroencephalography; Hemodynamics; Humans; Hypercapnia; Hypnotics and Sedatives; Infusions, Intravenous; Male; Oxygen; Piperidines; Remifentanil; Respiratory Mechanics; Sleep

Patients undergoing shoulder surgery in the beach chair position (BCP) under general anaesthesia may be at risk of cerebral desaturation. Increasing end-tidal carbon dioxide (EtCO2 ) is the most convenient and powerful method for the management of cerebral desaturation. The purpose of this study was to investigate the quantitative relationship between EtCO2 and cerebral oxygen saturation (rSO2 ) and to identify the associated influencing factors. Fifty-one patients undergoing arthroscopic shoulder surgery in the BCP under general anaesthesia completed this study. Desflurane and remifentanil were used, and EtCO2 was steadily increased and then decreased by adjusting the ventilator settings every 3 min. so that time lag of rSO2 response to EtCO2 changes could be delineated. Near-infrared spectroscopy was used to monitor rSO2 response. An indirect response model was used to examine the relationship between EtCO2 and rSO2 . To determine the relevant covariates, a stepwise approach was used. There was a linear relationship between rSO2 and EtCO2 with a slight delay in the peak of rSO2 relative to EtCO2 . Increase in end-tidal desflurane concentration led to a slower response of rSO2 to the changes of EtCO2 (p = 0.0002). The presence of diabetes mellitus reduced the reactivity of rSO2 to EtCO2 changes (p < 0.0001). This model-based approach revealed that diabetes mellitus attenuates the response of rSO2 to changes in EtCO2 . The management of cerebral desaturation by hypercapnia in patients with diabetes may be less effective than in non-diabetic patients under general anaesthesia with BCP.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, General; Arthroscopy; Carbon Dioxide; Desflurane; Diabetes Mellitus; Female; Humans; Hypercapnia; Isoflurane; Male; Middle Aged; Models, Biological; Oxygen; Piperidines; Posture; Remifentanil; Spectroscopy, Near-Infrared

The aim of this study was to investigate the effect of changes in end-tidal carbon dioxide tension (ETCO2) during remifentanil (Remi) infusion on oral tissue blood flow in rabbits. Eight male tracheotomized Japan White rabbits were anesthetized with sevoflurane under mechanical ventilation. The infusion rate of Remi was 0.4 μg/kg/min. Carbon dioxide was added to the inspired gas to change the inspired CO2 tension to prevent changes in the ventilating condition. Observed variables were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), common carotid artery blood flow (CCBF), tongue mucosal blood flow (TBF), mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF). The CCBF, TBF, BBF, UBF, and LBF values were increased, while MBF was decreased, under hypercapnia, and vice versa. The BBF, UBF, and LBF values were increased, while the MBF value was decreased, under hypercapnia during Remi infusion, and vice versa. The BBF, MBF, UBF, and LBF values, but not the CCBF and TBF values, changed along with ETCO2 changes during Remi infusion.

Topics: Alveolar Process; Anesthetics, Intravenous; Animals; Arterial Pressure; Blood Pressure; Bone Marrow; Capnography; Carbon Dioxide; Carotid Artery, Common; Heart Rate; Hypercapnia; Male; Mandible; Masseter Muscle; Mouth; Piperidines; Rabbits; Regional Blood Flow; Remifentanil; Respiration, Artificial; Tongue; Tracheostomy

Chronic intermittent hypoxia-hypercapnia (CIHH) exposure leads to learnning and memory deficits in rats. Overactivation of N-methyl-D-aspartate receptors(NMDARs) can lead to the death of neurons through a process termed excitotoxicity, which is involved in CIHH-induced cognitive deficits. Excessively activated NR2B (GluN2B)-containing NMDARs was reported as the main cause of excitotoxicity. The ERK1/2 (extracellular signal-regulated kinase 1/2) signaling cascade acts as a key component in NMDARs-dependent neuronal plasticity and survival. Ca2+/calmodulin-dependent protein kinase II (CaMKII), synapse-associated protein 102 (SAP102) and Ras GTPase-activating protein (SynGAP) have been shown to be involved in the regulation of NMDAR-ERK signalling cascade. Recent studies revealed statins (the HMG-CoA reductase inhibitor) have effect on the expression of NMDARs. The present study intends to explore the potential effect of lovastatin on CIHH-induced cognitive deficits and the NR2B-ERK signaling pathway.. Eighty male Sprague Dawley rats were randomly divided into five groups. Except for those in the control group, the rats were exposed to chronic intermittent hypoxia-hypercapnia (CIHH) (9 ∼ 11%O2, 5.5 ∼ 6.5%CO2) for 4 weeks. After lovastatin administration, the rats performed better in the Morris water maze test. Electron microscopy showed alleviated hippocampal neuronal synaptic damage. Further observation suggested that either lovastatin or ifenprodil (a selective NR2B antagonist) administration similarly downregulated NR2B subunit expression leading to a suppression of CaMKII/SAP102/SynGAP signaling cascade, which in turn enhanced the phosphorylation of ERK1/2. The phosphorylated ERK1/2 induced signaling cascade involving cAMP-response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) activation, which is responsible for neuroprotection.. These findings suggest that the ameliorative cognitive deficits caused by lovastatin are due to the downregulation of excessive NR2B expression accompanied by increased expression of ERK signaling cascade. The effect of NR2B in upregulating pERK1/2 maybe due, at least in part, to inactivation of CaMKII/SAP102/SynGAP signaling cascade.

Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Chronic Disease; Disease Models, Animal; Excitatory Amino Acid Antagonists; Gene Expression Regulation; GTPase-Activating Proteins; Hippocampus; Hypercapnia; Hypoxia; Learning Disabilities; Lovastatin; Male; MAP Kinase Signaling System; Maze Learning; Membrane Microdomains; Memory Disorders; Neuropeptides; Nootropic Agents; Piperidines; Pulmonary Disease, Chronic Obstructive; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Spatial Learning; Synaptosomes

Endocannabinoids are among the most intensively studied lipid mediators of cardiovascular functions. In the present study the effects of decreased and increased activity of the endocannabinoid system (achieved by cannabinoid-1 (CB1) receptor blockade and inhibition of cannabinoid reuptake, respectively) on the systemic and cerebral circulation were analyzed under steady-state physiological conditions and during hypoxia and hypercapnia (H/H).. In anesthetized spontaneously ventilating rats the CB1-receptor antagonist/inverse agonist AM-251 (10 mg/kg, i.v.) failed to influence blood pressure (BP), cerebrocortical blood flow (CoBF, measured by laser-Doppler flowmetry) or arterial blood gas levels. In contrast, the putative cannabinoid reuptake inhibitor AM-404 (10 mg/kg, i.v.) induced triphasic responses, some of which could be blocked by AM-251. Hypertension during phase I was resistant to AM-251, whereas the concomitant CoBF-increase was attenuated. In contrast, hypotension during phase III was sensitive to AM-251, whereas the concomitant CoBF-decrease was not. Therefore, CoBF autoregulation appeared to shift towards higher BP levels after CB1-blockade. During phase II H/H developed due to respiratory depression, which could be inhibited by AM-251. Interestingly, however, the concomitant rise in CoBF remained unchanged after AM-251, indicating that CB1-blockade potentially enhanced the reactivity of the CoBF to H/H. In accordance with this hypothesis, AM-251 induced a significant enhancement of the CoBF responses during controlled stepwise H/H.. Under resting physiological conditions CB1-receptor mediated mechanisms appear to have limited influence on systemic or cerebral circulation. Enhancement of endocannabinoid levels, however, induces transient CB1-independent hypertension and sustained CB1-mediated hypotension. Furthermore, enhanced endocannabinoid activity results in respiratory depression in a CB1-dependent manner. Finally, our data indicate for the first time the involvement of the endocannabinoid system and CB1-receptors in the regulation of the cerebral circulation during H/H and also raise the possibility of their contribution to the autoregulation of CoBF.

Topics: Animals; Arachidonic Acids; Arterial Pressure; Cerebrovascular Circulation; Endocannabinoids; Heart Rate; Hemodynamics; Hypercapnia; Hypertension; Hypoxia; Laser-Doppler Flowmetry; Male; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1

End tidal carbon dioxide (ETCO(2)) in non-intubated patients can be monitored using either sidestream or flow-through capnometry [Yamamori et al., J Clin Monit Comput 22(3):209-220, 2008]. The hypothesis of this validation study is that, flow-through capnometry will yield a more accurate estimate of ETCO(2) than sidestream capnometry when evaluated in a bench study during low tidal volumes and high oxygen administration via nasal cannula. Secondarily, when ETCO(2) from each is compared to arterial CO(2) (PaCO(2)) during a study in which healthy, non-intubated volunteers are tested under normocapnic, hypocapnic and hypercapnic conditions, the flow-through capnometer will resemble PaCO(2) more closely than the sidestream capnometer. This will be especially true during periods of lower minute ventilation and high oxygen flow rates via mask in non-intubated, remifentanil sedated, healthy volunteers whose physiologic deadspace is small.. The performance of a flow-through (cap-ONE, Nihon Kohden, Tokyo, Japan) and a sidestream (Microcap Smart CapnoLine Plus, Oridion Inc., Needham, MA) capnometer were compared in a bench study and a volunteer trial. A bench study evaluated ETCO(2) accuracy using waveforms generated via mechanical lungs during low tidal volumes and high oxygen flow rates. A volunteer study compared the ETCO(2) for each capnometer against PaCO(2) during sedation in which 8 l O(2) was delivered via mask rather than the nasal cannula.. In the bench study, the flow-through capnometer gave slightly higher values of ETCO(2) during high-flow oxygen and no discernable differences during variable tidal volumes. Bland and Altman plots comparing ETCO(2) to PaCO(2) showed essentially equal performance between the two capnometers in the volunteers.. Within a wide limit of agreement between the volunteer and bench study, flow-through and sidestream capnometry performed equally well during bench testing and in non-intubated, sedated patients.

Topics: Adolescent; Adult; Capnography; Carbon Dioxide; Computer Systems; Exhalation; Female; Humans; Hypercapnia; Hypnotics and Sedatives; Hypocapnia; Male; Monitoring, Physiologic; Oxygen; Piperidines; Remifentanil; Unconsciousness; Young Adult

Opioid binding to the cerebral blood vessels may affect vascular responsiveness and hence confound interpretation of blood oxygen level-dependent (BOLD) responses, which are usually interpreted as neuronal in origin. Opioid binding varies in different brain regions. It is unclear whether opioids alter neurovascular coupling, or whether their effects are purely neuronal. This study used BOLD functional magnetic resonance imaging (FMRI) to investigate the effect of a mu-opioid agonist remifentanil, on cerebrovascular CO(2) reactivity (being one component of neurovascular coupling). Hypercapnic challenges were delivered to human volunteers, while controlling potential opioid-induced respiratory depression. The BOLD signal increase to hypercapnia was compared before and during remifentanil administration. Remifentanil was shown not to have a generalised effect on CO(2) responsiveness in the cerebral vasculature. However, it caused a significant reduction in the positive BOLD response to hypercapnia in the bilateral primary sensorimotor cortices, bilateral extrastriate visual areas, left insula, left caudate nucleus, and left inferior temporal gyrus. We conclude that remifentanil does not modulate cerebrovascular CO(2) reactivity, as we saw no difference in BOLD response to hypercapnia in areas with high opioid receptor densities. We did however see a focal reduction in areas related to motor control and putative task activation, which we conclude to be related to changes in neuronal activity related to the sedative effects of remifentanil. Our method of controlling CO(2) levels effectively mitigated the potential confound of respiratory depression and allowed comparison over a similar range of CO(2) levels. We suggest that similar methodology should be used when investigating other potentially vasoactive compounds with FMRI.

Topics: Adult; Analgesics, Opioid; Blood Pressure; Brain Chemistry; Carbon Dioxide; Cerebrovascular Circulation; Female; Humans; Hypercapnia; Image Processing, Computer-Assisted; Infusions, Intravenous; Magnetic Resonance Imaging; Male; Oxygen; Piperidines; Remifentanil; Respiratory Function Tests

There is an increasing trend towards performing craniotomy awake. The challenge for the anaesthetist is to provide adequate analgesia and sedation, haemodynamic stability, and a safe airway, with an awake, cooperative patient for neurological testing.. The records of all patients who had awake craniotomy at our institution were reviewed. Patients were divided into three groups according to anaesthetic technique. Patients in Group 1 were sedated throughout the procedure. Patients in Groups 2 and 3 had an asleep-awake-asleep technique. Those in Group 2 were anaesthetized with a propofol infusion and fentanyl, and breathed spontaneously through a laryngeal mask airway (LMA). Patients in Group 3 had total i.v. anaesthesia with propofol and remifentanil, and ventilation was controlled using an LMA. We noted the incidence of complications in each group.. There were 99 procedures carried out between 1989 and 2002. Group 3 had the fewest complications. No patients in Group 3 developed hypercapnia (E'(CO(2)) >6 kPa), compared with all of the patients in Group 2. Patients in Group 1 had no E'(CO(2)) monitoring, but 7% developed airway obstruction. No patients in Group 3 required additional analgesia for pain, compared with 70% of patients in Group 2.. We have developed a technique for craniotomy, which facilitates awake neurological testing, is safe, and has good patient satisfaction.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Anesthesia; Anesthetics, Combined; Conscious Sedation; Craniotomy; Female; Fentanyl; Hemodynamics; Humans; Hypercapnia; Hypnotics and Sedatives; Intraoperative Complications; Laryngeal Masks; Male; Middle Aged; Piperidines; Propofol; Remifentanil

Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans.. The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard error.. A total of 94 responses were obtained at various drug combinations. When given separately, remifentanil and propofol depressed cardiorespiratory variables in a dose-dependent fashion (resting V(i) : 12.6 +/- 3.3% and 27.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; V(i) at fixed Petco of 55 mmHg: 44.3 +/- 3.9% and 57.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; blood pressure: 9.9 +/- 1.8% and 3.7 +/- 1.1% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively). When given in combination, their effect on respiration was synergistic (greatest synergy observed for resting V(i)). The effects of both drugs on heart rate and blood pressure were modest, with additive interactions when combined. Over the dose range studied, remifentanil had no effect on bispectral index even when combined with propofol (inert interaction).. These data show dose-dependent effects on respiration at relatively low concentrations of propofol and remifentanil. When combined, their effect on respiration is strikingly synergistic, resulting in severe respiratory depression.

Topics: Adult; Analgesics, Opioid; Anesthetics, Intravenous; Blood Pressure; Carbon Dioxide; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Heart Rate; Hemodynamics; Humans; Hypercapnia; Male; Models, Biological; Piperidines; Propofol; Remifentanil; Respiratory Mechanics

We recently concluded that constriction of basilar artery due to respiration-induced hypocapnia in rabbits with acute metabolic alkalosis and accompanying compensatory hypercapnia was independent of NO and K(ATP) channels. Based on reports that endothelin-1-mediated hypocapnic constriction of the rabbit basilar artery in vitro, we further investigated whether the respiration-induced hypocapnic constriction was endothelin-1 mediated. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. The ET(A) plus ET(B) receptor antagonist, PD145065 (1 microM), and the selective ET(A) receptor antagonist, BQ610 (3 microM), completely relaxed the hypocapnic constriction, as determined in a cranial window. Unexpectedly, the ET(B) receptor antagonists, BQ788 and RES-701-1 (3 microM), relaxed the constriction by 72.1+/-2.8% (4) and 77.2+/-8.7% (5), respectively (means+/-S.E. (n)). To investigate whether the large magnitudes of relaxation to both ET(A) and ET(B) receptor antagonists were due to nonselectivity of the antagonists, the effects of the antagonists on the constriction to exogenous endothelin-1 were evaluated. BQ610, BQ788, and RES-701-1 relaxed the 3-5 nM endothelin-1 constriction by only 64.3+/-7.6% (4), 43.5+/-8.5% (5), and 26.7+/-4.8% (3) (means+/-S.E. (n)), respectively, consistent with the selective blocking action of these antagonists. To investigate whether the greater magnitude of BQ610, BQ788, and RES-701-1 relaxation of hypocapnic constricted versus exogenous endothelin-1-constricted vessels was due to differences between constriction elicited by endogenous versus exogenous endothelin-1, the effects of the endothelin receptor antagonists on constriction to isocapnic alkaline suffusate were evaluated. PD145065 (1 microM) and 0.1 mM phosphoramidon, an endothelin-converting enzyme inhibitor, inhibited the constriction to isocapnic alkaline suffusate by 83.8+/-7.8% (6) and 74.3+/-9.7% (8) (means+/-S.E. (n)), respectively, consistent with the endothelin-1 dependency of the constriction. BQ610, BQ788, and RES-701-1 relaxed the isocapnic alkaline suffusate constriction by 74.9+/-6.7% (5), 65.5+/-6.4% (5), and 78.0+/-6.5% (4) (means+/-S.E. (n)), respectively. Thus, the relaxation profile to the selective endothelin receptor antagonists in isocapnic alkaline constricted vessels more closely approximated the relaxation profile observed in hypocapnic constricted as compared to endothelin-1-constricted vessels. Hypocapnia did not alter the

Topics: Alkalosis; Animals; Basilar Artery; Blood Gas Analysis; Carbon Dioxide; Endothelins; Hydrogen-Ion Concentration; Hypercapnia; Hypocapnia; Oligopeptides; Peptides, Cyclic; Piperidines; Rabbits; Receptors, Endothelin; Vasoconstriction

Topics: Anesthetics; Animals; Cerebrovascular Circulation; Haplorhini; Hypercapnia; Hypoxia; Intracranial Pressure; Macaca; Phencyclidine; Piperidines

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