RESUMEN
The widely prescribed opioid oxycodone may cause lethal respiratory depression. We compared the effects of oxycodone on breathing and antinociception in healthy young volunteers. After pharmacokinetic/pharmacodynamic (PK/PD) modeling, we constructed utility functions to combine the wanted and unwanted end points into a single function. We hypothesized that the function would be predominantly negative over the tested oxycodone concentration range. Twenty-four male and female volunteers received 20 (n = 12) or 40 (n = 12) mg oral oxycodone immediate-release tablets. Hypercapnic ventilatory responses (visit 1) or responses to 3 nociceptive assays (pain pressure, electrical, and thermal tests; visit 2) were measured at regular intervals for 7 hours. the PK/PD analyses, that included carbon dioxide kinetics, stood at the basis of the utility function: probability of antinociception minus probability of respiratory depression. Oxycodone had rapid onset/offset times (30-40 minutes) with potency values (effect-site concentration causing 50% of effect) ranging from 0.05 to 0.13 ng/mL for respiratory variables obtained at hypercapnia and antinociceptive responses. Ventilation at an extrapolated end-tidal carbon dioxide partial pressure of 55 mmHg, was used for creation of 3 utility functions, one for each of the nociceptive tests. Contrary to expectation, the utility functions were close to zero or positive over the clinical oxycodone concentration range. The similar or better likelihood for antinociception relative to respiratory depression may be related to oxycodone's receptor activation profile or to is high likeability that possibly alters the modulation of nociceptive input. Oxycodone differs from other µ-opioids, such as fentanyl, that have a consistent negative utility.
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Oxicodona , Insuficiencia Respiratoria , Humanos , Masculino , Femenino , Oxicodona/efectos adversos , Hipercapnia/inducido químicamente , Dióxido de Carbono/efectos adversos , Analgésicos Opioides/efectos adversos , Insuficiencia Respiratoria/inducido químicamenteRESUMEN
Fetal alcohol spectrum disorder (FASD) has been linked to numerous poor neurological outcomes as well as impairments in respiratory neural control. Females are known to metabolize ethanol (EtOH) differently than males suggesting a sexual dimorphic sensitivity to EtOH exposure. We used a rodent model of FASD to investigate whether EtOH disrupts respiratory neural control. Rat pups received a single intraperitoneal injection of 2 different doses (0.8 mg/g or 4.4 mg/g) of EtOH. Whole-body plethysmography was used â¼24 h later to assess ventilatory responses to acute hypoxia (HVR) and hypercapnia (HCVR). Females treated with 4.4 mg/g of EtOH exhibited an attenuated HVR and HCVR, but there was no effect on males, and no effect of 0.8 mg/g on either sex. There was unexpected mortality of unknown causes, especially in females, that occurred 2-3 days after EtOH administration. These data suggest that important ventilatory defense responses in females are impaired following developmental EtOH exposure, and this may be associated with increased risk of later death.
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Trastornos del Espectro Alcohólico Fetal , Embarazo , Masculino , Humanos , Femenino , Ratas , Animales , Roedores , Etanol/toxicidad , Hipercapnia/inducido químicamente , HipoxiaRESUMEN
The study investigated the role of alpha2-adrenergic receptors of the caudal raphe region in the sympathetic and cardiovascular responses to the acute intermittent hypercapnia (AIHc). Urethane-anesthetized, vagotomized, mechanically ventilated Sprague-Dawley rats (n=38) were exposed to the AIHc protocol (5×3 min, 15 % CO2+50 % O2) in hyperoxic background (50 % O2). alpha2-adrenergic receptor antagonist-yohimbine was applied intravenously (1 mg/kg, n=9) or microinjected into the caudal raphe region (2 mM, n=12) prior to exposure to AIHc. Control groups of animals received saline intravenously (n=7) or into the caudal raphe region (n=10) prior to exposure to AIHc. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored before exposure to the AIHc protocol (T0), during five hypercapnic episodes (THc1-5) and at 15 min following the end of the last hypercapnic episode (T15). Following intravenous administration of yohimbine, RSNA was significantly greater during THc1-5 and at T15 than in the control group (P<0.05). When yohimbine was microinjected into the caudal raphe region, AIHc elicited greater increases in RSNA during THc1-5 when compared to the controls (THc1: 138.0+/-4.0 % vs. 123.7+/-4.8 %, P=0.032; THc2: 137.1+/-5.0 % vs. 124.1+/-4.5 %, P=0.071; THc3: 143.1+/-6.4 % vs. 122.0±4.8 %, P=0.020; THc4: 146.1+/-6.2 % vs. 120.7+/-5.7 %, P=0.007 and THc5: 143.2+/-7.7 % vs. 119.2+/-7.2 %, P=0.038). During THc1-5, significant decreases in HR from T0 were observed in all groups, while changes in MAP were observed in the group that received yohimbine intravenously. These findings suggest that blockade of the alpha2-adrenegic receptors in the caudal raphe region might have an important role in sympathetic responses to AIHc.
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Hipercapnia , Sistema Nervioso Simpático , Animales , Presión Sanguínea/fisiología , Frecuencia Cardíaca , Hipercapnia/inducido químicamente , Núcleos del Rafe , Ratas , Ratas Sprague-Dawley , Receptores AdrenérgicosRESUMEN
BACKGROUND: Operator-directed nurse-administered (ODNA) sedation with propofol (PRO) is the preferred sedation technique for catheter ablation of atrial fibrillation (AF) in many centers. OBJECTIVE: The purpose of this study was to investigate whether dexmedetomidine (DEX), an α2-adrenergic receptor agonist, is superior to propofol. METHODS: We randomized 160 consecutive patients undergoing first AF ablation to ODNA sedation by DEX (DEX group) vs PRO (PRO group), according to a standardized protocol. Patients were unaware of treatment allocation. The primary endpoint was a composite of inefficient sedation, termination/change of sedation protocol or procedure abortion, hypercapnia (transcutaneous CO2 >55 mm Hg), hypoxemia (SpO2 <90%) or intubation, prolonged hypotension (systolic blood pressure <80 mm Hg), and sustained bradycardia necessitating cardiac pacing. Secondary endpoints were the components of the primary endpoint and patient satisfaction with procedural sedation, as assessed by a standardized questionnaire given the day after ablation. RESULTS: The primary endpoint occurred in 15 DEX group and 25 PRO group patients (19% vs 31%; P = .068). Hypercapnia was significantly more frequent in PRO group patients (29% vs 10%; P = .003). There was no significant difference for the other components of the primary endpoint, and no procedure was aborted. Patient satisfaction was significantly better among PRO group patients (visual analogue scale 0-100; median 100 in PRO group vs median 93 in DEX group; P <.001). CONCLUSION: Efficacy of ODNA sedation with DEX was not different from that with PRO. Hypercapnia occurs less frequently with DEX, but patient satisfaction is better with PRO sedation. In selected patients, DEX may be used as an alternative to PRO for ODNA sedation during AF ablation.
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Fibrilación Atrial , Ablación por Catéter , Dexmedetomidina , Propofol , Ablación por Catéter/efectos adversos , Dexmedetomidina/efectos adversos , Humanos , Hipercapnia/inducido químicamente , Hipercapnia/cirugía , Hipnóticos y SedantesRESUMEN
The evidence is mounting for a role for abnormal signaling of the stress peptide pituitary adenylate cyclase activating polypeptide (PACAP) and its canonical receptor PAC1 in the pathogenesis of sudden infant death syndrome. In this study, we investigated whether the PACAP receptors PAC1 or VPAC2 are involved in the neonatal cardiorespiratory response to hypercapnic stress. We used head-out plethysmography and surface ECG electrodes to assess cardiorespiratory responses to an 8% hypercapnic challenge in unanesthetized and spontaneously breathing 4-day-old PAC1 or VPAC2 knockout (KO) and wild-type mouse pups. We demonstrate that compared with WTs, breathing frequency (RR) and minute ventilation ([Formula: see text]) in PAC1 KO pups were significantly blunted in response to hypercapnia. Although heart rate was unaltered in PAC1 KO pups during hypercapnia, heart rate recovery posthypercapnia was impaired. In contrast, cardiorespiratory impairments in VPAC2 KO pups were limited to only an overall higher tidal volume (VT), independent of treatment. These findings suggest that PACAP signaling through the PAC1 receptor plays a more important role than signaling through the VPAC2 receptor in neonatal respiratory responses to hypercapnia. Thus deficits in PACAP signaling primarily via PAC1 may contribute to the inability of infants to mount an appropriate protective response to homeostatic stressors in childhood disorders such as SIDS.
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Dióxido de Carbono/toxicidad , Frecuencia Cardíaca/efectos de los fármacos , Hipercapnia/inducido químicamente , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/metabolismo , Receptores de Tipo II del Péptido Intestinal Vasoactivo/metabolismo , Fenómenos Fisiológicos Respiratorios/efectos de los fármacos , Animales , Animales Recién Nacidos , Apnea , Peso Corporal , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Genotipo , Hipercapnia/metabolismo , Masculino , Ratones , Ratones Noqueados , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/genética , Receptores de Tipo II del Péptido Intestinal Vasoactivo/genética , TemperaturaRESUMEN
One of the possible causes of death in epilepsy is breathing disorders, especially apneas, which lead to an increase in CO2 levels (hypercapnia) and/or a decrease in O2 levels in arterial blood (hypoxemia). The respiratory neurons located in the ventral brainstem respiratory column are the main groups responsible for controlling breathing. Recent data from our group demonstrated respiratory changes in two experimental models of epilepsy, i.e. audiogenic epilepsy, and amygdala rapid kindling. Here, we aimed to evaluate respiratory changes in the classic model of temporal lobe epilepsy induced by intra-hippocampal injection of pilocarpine. Adult Wistar rats with stainless-steel cannulas implanted in the hippocampus region were used. The animals were submitted to pilocarpine injection (2.4 mg/µL, N = 12-15) or saline (N = 9) into the hippocampus. The respiratory parameters analyzed by whole-body plethysmography were respiratory rate (fR), tidal volume (VT) and ventilation (VE). Respiratory mechanics such as Newtonian airway resistance (Rn), viscance of the pulmonary parenchyma (G) and the elastance of the pulmonary parenchyma (H) were also investigated. No changes in baseline breathing were detected 15 or 30 days after pilocarpine-induced status epilepticus (SE). However, 30 days after pilocarpine-induced SE, a significant reduction in VE was observed during hypercapnic (7% CO2) stimulation, without affecting the hypoxia (8% O2) ventilatory response. We also did not observe changes in respiratory mechanics. The present results suggest that the impairment of the hypercapnia ventilatory response in pilocarpine-induced SE could be related to a presumable degeneration of brainstem respiratory neurons but not to peripheral mechanisms.
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Células Quimiorreceptoras/efectos de los fármacos , Pilocarpina/toxicidad , Respiración/efectos de los fármacos , Estado Epiléptico/inducido químicamente , Estado Epiléptico/fisiopatología , Volumen de Ventilación Pulmonar/efectos de los fármacos , Animales , Células Quimiorreceptoras/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Hipercapnia/inducido químicamente , Hipercapnia/fisiopatología , Inyecciones Intraventriculares , Masculino , Agonistas Muscarínicos/administración & dosificación , Agonistas Muscarínicos/toxicidad , Pilocarpina/administración & dosificación , Ratas , Ratas Wistar , Mecánica Respiratoria/efectos de los fármacos , Mecánica Respiratoria/fisiología , Volumen de Ventilación Pulmonar/fisiologíaAsunto(s)
2,4-Dinitrofenol/envenenamiento , Paro Cardíaco/inducido químicamente , Hipercapnia/inducido químicamente , Hipertermia/inducido químicamente , Rigidez Muscular/inducido químicamente , Adulto , Fármacos Antiobesidad/envenenamiento , Ecocardiografía , Electrocardiografía , Paro Cardíaco/terapia , Humanos , Masculino , Intento de SuicidioRESUMEN
Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level-dependent (BOLD) response. This is achieved by scaling, using information from a perfusion-sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath-hold task. In this work, we seek for a validation of the use of the resting-state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth-dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia-induced signal changes (tSDhc ) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSDhc ( R2 = 0.92 ± 0.06) and somewhat reduced for RSFA and M ( R2 = 0.62 ± 0.19). Laminar profiles of RSFA-normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We conclude that RSFA may replace the scaling factor tSDhc for normalizing the laminar BOLD response.
Asunto(s)
Corteza Cerebral/diagnóstico por imagen , Conectoma/normas , Hipercapnia/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/normas , Imagen por Resonancia Magnética/normas , Adulto , Femenino , Humanos , Hipercapnia/inducido químicamente , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Respiratory function is fundamental in the practice of anesthesia. Knowledge of basic physiologic principles of respiration assists in the proper implementation of daily actions of induction and maintenance of general anesthesia, delivery of mechanical ventilation, discontinuation of mechanical and pharmacologic support, and return to the preoperative state. The current work provides a review of classic physiology and emphasizes features important to the anesthesiologist. The material is divided in two main sections, gas exchange and respiratory mechanics; each section presents the physiology as the basis of abnormal states. We review the path of oxygen from air to the artery and of carbon dioxide the opposite way, and we have the causes of hypoxemia and of hypercarbia based on these very footpaths. We present the actions of pressure, flow, and volume as the normal determinants of ventilation, and we review the resulting abnormalities in terms of changes of resistance and compliance.
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Anestesia General/normas , Anestesiólogos/educación , Anestesiólogos/normas , Mecánica Respiratoria/efectos de los fármacos , Mecánica Respiratoria/fisiología , Anestesia General/efectos adversos , Dióxido de Carbono/metabolismo , Humanos , Hipercapnia/inducido químicamente , Hipercapnia/fisiopatología , Hipoxia/inducido químicamente , Hipoxia/fisiopatología , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Intercambio Gaseoso Pulmonar/fisiología , Respiración Artificial/métodos , Volumen de Ventilación Pulmonar/efectos de los fármacos , Volumen de Ventilación Pulmonar/fisiologíaRESUMEN
Reptilian embryos often face challenging environmental gas compositions during incubation, which may inflict long-lasting effects in the individuals' physiological responses. These conditions can have a lasting effect on the animal into juvenile life as chronic prenatal exposure to hypercarbia results in enlarged hatchling organ size, higher growth rate and resting metabolic rate, although relatively smaller increment in metabolic scope during digestion. Therefore, we wanted to verify whether prenatal hypercarbia exposure would cause persistent effects on morphology and physiological responses in C. serpentina. We measured organ masses and cardiovascular parameters in five years old turtles incubated either under 3.5% hypercarbia (H3.5) or normoxia (N21). We expected that: i) organ masses of H3.5 would be bigger than N21; ii) acute exposure to hypoxia should decrease blood flows in H3.5, since metabolic scope is presumably reduced in this group. As hypoxia exposure elicits catecholamine release, we also tested cardiovascular responses to adrenaline injection. Lungs and stomach exhibited higher growth rates in H3.5. Divergent cardiovascular responses between groups to adrenaline injection were observed for heart rate, pulmonary blood flow, pulmonary mean arterial pressure, blood shunt, systemic stroke volume, and stomach perfusion. Hypoxia caused decreased systemic blood flow and cardiac output, systemic and total stroke volume, and systemic vascular conductance in H3.5. These variables were unaffected in N21, but pulmonary flow and stroke volume, and stomach blood perfusion were reduced. These data support the hypothesis that exposure to hypercarbia during embryonic development has long term effects on organ morphology and cardiovascular responses of C. serpentina.
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Dióxido de Carbono/toxicidad , Sistema Cardiovascular/fisiopatología , Desarrollo Embrionario/efectos de los fármacos , Hipercapnia/fisiopatología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Animales , Presión Sanguínea/efectos de los fármacos , Catecolaminas/metabolismo , Embrión no Mamífero/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Hipercapnia/inducido químicamente , Hipoxia/inducido químicamente , Hipoxia/fisiopatología , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Tortugas/crecimiento & desarrolloRESUMEN
Functional connectivity MRI, based on Blood-Oxygenation-Level-Dependent (BOLD) signals, is typically performed while the subject is at rest. On the other hand, BOLD is also widely used in physiological imaging such as cerebrovascular reactivity (CVR) mapping using hypercapnia (HC) as a modulator. We therefore hypothesize that hypercapnia BOLD data can be used to extract FC metrics after factoring out the effects of the physiological modulation, which will allow simultaneous assessment of neural and vascular function and may be particularly important in populations such as aging and cerebrovascular diseases. The present work aims to systematically examine the feasibility of hypercapnia BOLD-based FC mapping using three commonly applied analysis methods, specifically dual-regression Independent Component Analysis (ICA), region-based FC matrix analysis, and graph-theory based network analysis, in a large cohort of 170 healthy subjects ranging from 20 to 88 years old. To validate the hypercapnia BOLD results, we also compared these FC metrics with those obtained from conventional resting-state data. ICA analysis of the hypercapnia BOLD data revealed FC maps that strongly resembled those reported in the literature. FC matrix using region-based analysis showed a correlation of 0.97 on the group-level and 0.54⯱â¯0.10 on the individual-level, when comparing between hypercapnia and resting-state results. Although the correspondence on the individual-level was moderate, this was primarily attributed to variations intrinsic to FC mapping, because a corresponding resting-vs-resting comparison in a sub-cohort (Nâ¯=â¯39) revealed a similar correlation of 0.57⯱â¯0.09. Graph-theory computations were also feasible in hypercapnia BOLD data and indices of global efficiency, clustering coefficient, modularity, and segregation were successfully derived. Hypercapnia FC results revealed age-dependent differences in which within-network connections generally exhibited an age-dependent decrease while between-network connections showed an age-dependent increase.
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Cerebelo/fisiología , Corteza Cerebral/fisiología , Conectoma/métodos , Hipercapnia/fisiopatología , Imagen por Resonancia Magnética/métodos , Red Nerviosa/fisiología , Acoplamiento Neurovascular/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Hipercapnia/inducido químicamente , Hipercapnia/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Adulto JovenRESUMEN
The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.
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Anestesia General , Anestésicos Generales/farmacología , Fenómenos Cronobiológicos/fisiología , Ketamina/farmacología , Pentobarbital/farmacología , Tiletamina/farmacología , Zolazepam/farmacología , Anestesia General/efectos adversos , Anestesia General/tendencias , Anestésicos Generales/efectos adversos , Anestésicos Generales/sangre , Animales , Análisis de los Gases de la Sangre/métodos , Fenómenos Cronobiológicos/efectos de los fármacos , Combinación de Medicamentos , Femenino , Hipercapnia/sangre , Hipercapnia/inducido químicamente , Hipoxia/sangre , Hipoxia/inducido químicamente , Ketamina/efectos adversos , Pentobarbital/efectos adversos , Ratas , Ratas Wistar , Tiletamina/efectos adversos , Zolazepam/efectos adversosRESUMEN
Cerebrovascular reactivity (CVR) is a measure of vascular response to a vasoactive stimulus, and can be used to assess the health of the brain vasculature. In this current study we used different analyses of BOLD fMRI responses to CO2 to provide a number of metrics including ramp and step CVR, speed of response and transfer function analysis (TFA). 51 healthy control volunteers between the ages of 18-85 (26 males) were recruited and scanned at 3T field strength. Atlases reflecting voxel-wise means and standard deviations were compiled to assess possible differences in these metrics between four age cohorts. Testing was carried out using an automated computer-controlled gas blender to induce hypercapnia in a step and ramp paradigm, and monitoring end-tidal partial pressures of CO2 (PETCO2) and O2 (PETO2). No significant differences were found for resting PETCO2 values between cohorts. Ramp CVR decreased significantly with age in white matter frontal regions comprising the ACA-MCA watershed area, a finding that may be indicative of age related changes. Similarly, TFA showed that gain was reduced in the left white matter ACA-MCA watershed area as well as the posterior and anterior cingulate cortex, and superior frontal gyrus in the oldest compared to youngest cohort. These findings, detailing changes in cerebrovascular regulation in the healthy aging brain should prove useful in mapping areas of dysregulated blood flow in individuals with vascular risk factors especially those at risk for developing vascular dementia.
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Envejecimiento/fisiología , Dióxido de Carbono/farmacología , Corteza Cerebral/fisiología , Lóbulo Frontal/fisiología , Neuroimagen Funcional/métodos , Acoplamiento Neurovascular/fisiología , Sustancia Blanca/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Femenino , Lóbulo Frontal/irrigación sanguínea , Lóbulo Frontal/diagnóstico por imagen , Giro del Cíngulo/irrigación sanguínea , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiología , Humanos , Hipercapnia/inducido químicamente , Hipercapnia/diagnóstico por imagen , Hipercapnia/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Prefrontal/irrigación sanguínea , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Sustancia Blanca/irrigación sanguínea , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Pulmonary vein isolation (PVI) is generally performed under analgosedation, but sedation protocols vary and no optimal protocol has been defined. We investigated procedural, respiratory and hemodynamic parameters in patients undergoing PVI using analgosedation either with or without midazolam. METHODS: In a prospective observational study, we compared nâ¯=â¯43 consecutive patients (54% male, mean age 62â¯years) undergoing PVI using analgosedation either with or without midazolam added to propofol and fentanyl. A priori defined outcome measures were propofol dose, hypotension (systolic blood pressure <100â¯mmâ¯Hg or >30â¯mmâ¯Hg drop from baseline), acidosis (pHâ¯<â¯7.30), hypercapnia (pC02â¯>â¯55â¯mmâ¯Hg) and hypoxemia (transdermal oxygen saturationâ¯<â¯90%). RESULTS: Patients in the midazolam group (nâ¯=â¯22) received a mean dose of 3⯱â¯1.5â¯mg midazolam and required less propofol than those in the no-midazolam group (nâ¯=â¯21, 473⯱â¯189â¯mg vs. 618⯱â¯219â¯mg, pâ¯=â¯.03). Incidence of hypotension did not differ between groups (54.5% vs. 61.9%, pâ¯=â¯.63). Acidosis was more frequent in the midazolam group (63.6% vs. 28.6%, pâ¯=â¯.03), as was hypercapnia (50% vs. 14.3%, pâ¯=â¯.03) while occurrence of hypoxemia did not differ between groups (22.7 vs. 33.3%, pâ¯=â¯.5). CONCLUSION: Patients receiving midazolam had a more than doubled risk of respiratory depression as mirrored by hypercapnia and acidosis, but not hypoxemia. These observations may help in choosing an analgosedation and monitoring protocol for PVI.
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Acidosis/inducido químicamente , Anestésicos Intravenosos/efectos adversos , Hipercapnia/inducido químicamente , Hipnóticos y Sedantes/efectos adversos , Midazolam/efectos adversos , Venas Pulmonares/cirugía , Acidosis/diagnóstico por imagen , Anciano , Anestésicos Intravenosos/administración & dosificación , Quimioterapia Combinada , Femenino , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Estudios de Seguimiento , Humanos , Hipercapnia/diagnóstico por imagen , Hipnóticos y Sedantes/administración & dosificación , Masculino , Midazolam/administración & dosificación , Persona de Mediana Edad , Propofol/administración & dosificación , Propofol/efectos adversos , Estudios Prospectivos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/efectos de los fármacosRESUMEN
Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD58-67) in a whole-body exposure chamber, and given oxygen (0.8 FiO2) or air (0.21 FiO2) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.
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Gasto Cardíaco/efectos de los fármacos , Sustancias para la Guerra Química/toxicidad , Cloro/toxicidad , Oxígeno/farmacología , Insuficiencia Respiratoria , Enfermedad Aguda , Animales , Hipercapnia/inducido químicamente , Hipercapnia/tratamiento farmacológico , Hipercapnia/fisiopatología , Masculino , Ratas , Ratas Sprague-Dawley , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/fisiopatologíaRESUMEN
INTRODUCTION: Astronauts undergo CO2 exposure training to recognize their symptoms that can arise acutely both on the ground and in spaceflight. This article describes acute CO2 exposure training at NASA and examines the symptoms reported by astronauts during training. METHODS: In a controlled training environment, astronauts are exposed to up to 8% CO2 (60 mmHg) by a rebreathing apparatus. Symptoms are reported using a standard form. RESULTS: Symptom documentation forms between April 1994 and February 2012 were obtained for 130 astronauts. The number of symptoms reported per session out of the possible 24 was related to age and sex, with those older slightly more likely to report symptoms. Women reported more symptoms on average than men (men: 3.7, women: 4.7). Respiratory symptoms (90%), flushing sensation/sweating (56%), and dizziness/feeling faint/lightheadedness (43%) were the top symptoms. Only headache reached statistical significance in differences between men (13%) and women (37%) after adjustment for multiple testing. Among those with multiple training sessions, respiratory symptoms were the most consistently reported. DISCUSSION: CO2 exposure training is an important tool to educate astronauts about their potential acute CO2 symptoms. Wide interindividual and temporal variations were observed in symptoms reported during astronaut CO2 exposure training. Headache could not be relied on as a marker of acute exposure during testing since fewer than half the subjects reported it. Our results support periodic refresher training since symptoms may change over time. Further study is needed to determine the optimal interval of training to maximize symptom recognition and inform operational decisions.Law J, Young M, Alexander D, Mason SS, Wear ML, Méndez CM, Stanley D, Meyers Ryder V, Van Baalen M. Carbon dioxide physiological training at NASA. Aerosp Med Hum Perform. 2017; 88(10):897-902.
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Astronautas , Dióxido de Carbono/efectos adversos , Hipercapnia/fisiopatología , Simulación del Espacio , United States National Aeronautics and Space Administration , Adulto , Medicina Aeroespacial , Factores de Edad , Mareo/etiología , Disnea/etiología , Femenino , Rubor/etiología , Cefalea/etiología , Humanos , Hipercapnia/inducido químicamente , Hipercapnia/complicaciones , Masculino , Persona de Mediana Edad , Factores Sexuales , Sudoración , Taquipnea/etiología , Estados UnidosRESUMEN
The A5 area at the ventrolateral pons contains noradrenergic neurons connected with other medullary areas involved in the cardiorespiratory control. Its contribution to the cardiorespiratory regulation was previously evidenced in anesthetized conditions. In the present study, we investigated the involvement of the A5 noradrenergic neurons to the basal and chemoreflex control of the sympathetic and respiratory activities in unanesthetized conditions. A5 noradrenergic neurons were lesioned using microinjections of anti-dopamine ß-hydroxylase saporin (anti-DßH-SAP). After 7-8days, we evaluated the arterial pressure levels, heart rate and minute ventilation in freely moving adult rats (280-350g) as well as recorded from thoracic sympathetic (tSN) and phrenic nerves (PN) using the arterially perfused in situ preparation of juvenile rats (80-90g). Baseline cardiovascular, sympathetic and respiratory parameters were similar between control (n=7-8) and A5-lesioned rats (n=5-6) in both experimental preparations. In adult rats, lesions of A5 noradrenergic neurons did not modify the reflex cardiorespiratory adjustments to hypoxia (7% O2) and hypercapnia (7% CO2). In the in situ preparations, the sympatho-excitation, but not the PN reflex response, elicited by either the stimulation of peripheral chemoreceptors (ΔtSN: 110±12% vs 58±8%, P<0.01) or hypercapnia (ΔtSN: 9.5±1.4% vs 3.9±1.7%, P<0.05) was attenuated in A5-lesioned rats compared to controls. Our data demonstrated that A5 noradrenergic neurons are part of the circuitry recruited for the processing of sympathetic response to hypoxia and hypercapnia in unanesthetized conditions.
Asunto(s)
Neuronas Adrenérgicas/fisiología , Hipercapnia/fisiopatología , Puente/citología , Sistema Nervioso Simpático/fisiología , Vigilia , Análisis de Varianza , Animales , Anticuerpos Monoclonales/toxicidad , Presión Sanguínea/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hipercapnia/inducido químicamente , Masculino , Puente/efectos de los fármacos , Puente/lesiones , Ventilación Pulmonar/fisiología , Ratas , Ratas Wistar , Proteínas Inactivadoras de Ribosomas Tipo 1/toxicidad , Saponinas/toxicidad , Saporinas , Sistema Nervioso Simpático/efectos de los fármacos , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
INTRODUCTION: Evidence for the use of non-anesthesiologist-administered propofol for sedation during flexible bronchoscopy is scarce. The main objective of this study was to determine whether non-anesthesiologist-administered propofol balanced sedation was related to higher transcutaneous CO2 pressure compared with current guideline-based sedation (combination midazolam and opioid). Secondary outcomes were post-procedural recuperation time, patient satisfaction and frequency of adverse events. METHODS: In this randomized controlled trial we included data from outpatients aged 18 years or older with an indication for flexible bronchoscopy in a university hospital in northern Mexico. RESULTS: Ninety-one patients were included: 42 in the midazolam group and 49 in the propofol group. During 60min of transcutaneous capnometry monitoring, mean transcutaneous CO2 pressure values did not differ significantly between groups (43.6 [7.5] vs. 45.6 [9.6]mmHg, P=.281). Propofol was related with a high Aldrete score at 5, 10, and 15min after flexible bronchoscopy (9 [IQR 6-10] vs. 10 [9,10], P=.006; 9 [8-10] vs. 10 [IQR 10-10], P<.001 and 10 [IQR 9-10] vs. 10 [10], respectively) and with high patient satisfaction on a visual analogue scale of 1 (not satisfied) to 10 (very satisfied) (8.41 [1.25] vs. 8.97 [0.98], P=.03). Frequency of adverse events was similar among groups (30.9% vs. 22.4%, P=.47). CONCLUSION: Compared with guideline-recommended sedation, non-anesthesiologist-administered propofol balanced sedation is not associated with higher transcutaneous CO2 pressure or with more frequent adverse effects. Propofol use is associated with faster sedation recovery and with high patient satisfaction. CLINICAL TRIAL REGISTRATION: NCT02820051.
Asunto(s)
Broncoscopía , Dióxido de Carbono/sangre , Sedación Profunda/efectos adversos , Hipercapnia/inducido químicamente , Hipnóticos y Sedantes/efectos adversos , Asistentes de Enfermería , Propofol/efectos adversos , Adulto , Anciano , Atención Ambulatoria , Monitoreo de Gas Sanguíneo Transcutáneo , Sedación Profunda/métodos , Sedación Profunda/psicología , Femenino , Hospitales Universitarios , Humanos , Hipercapnia/prevención & control , Hipnóticos y Sedantes/administración & dosificación , Masculino , Midazolam/administración & dosificación , Midazolam/efectos adversos , Persona de Mediana Edad , Nalbufina/administración & dosificación , Nalbufina/efectos adversos , Satisfacción del Paciente , Guías de Práctica Clínica como Asunto , Propofol/administración & dosificación , Estudios Prospectivos , Método Simple CiegoRESUMEN
The present study was designed to investigate whether H2S could improve the respiratory responses to hypercapnia blunted by prenatal CSE in neonatal rats in vivo. Respiratory activities were recorded with head-out body plethysmography. The results showed that during baseline, respiratory frequency (FR), tidal volume (VT) and minute ventilation (VE) were similar among tested groups; frequency of spontaneous apnea (FSA), not post-sigh apnea (FPA), was significantly elevated by prenatal CSE. During hypercapnia, the increases in FR and VE were significantly reduced, but VT was not markedly different, in CSE group; both FSA and FPA were decreased, although FSA remained higher in CSE group. All the aforementioned effects induced by CSE on respiratory activities were relieved by NaHS (donor of H2S, 56µmol/kg by intraperitoneal injection). These data indicate that H2S could ameliorate the disruption of respiratory responses to hypercapnia induced by prenatal CSE in neonatal rats.
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Fumar Cigarrillos/efectos adversos , Gasotransmisores/uso terapéutico , Sulfuro de Hidrógeno/uso terapéutico , Hipercapnia/inducido químicamente , Hipercapnia/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Femenino , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ventilación Pulmonar , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Pregabalin is often used for the treatment of neuropathic pain in patients with spinal cord injury (SCI). We reported a patient with C5 [S(C5/C6)] ASIA Impairment Scale C SCI due to cervical myelopathy who presented CO2 retention when taking a therapeutic dosage of pregabalin. An 88-year-old patient with cervical SCI was transferred to the department of physical medicine and rehabilitation. When he had transferred, his neuropathic pain had been treated with 150-mg pregabalin per day (75 mg twice a day); however, he still exhibited severe neuropathic pain with a Numeric Pain Rating Scale score of 7 to 8. Dosage for the pregabalin increased from 150 mg/d (75 mg twice a day) to 225 mg/d (150 mg at morning and 75 mg at dinner). That afternoon, he presented drowsiness and confusion, and arterial blood gas analysis (ABGA) demonstrated respiratory acidosis with CO2 retention; pH, 7.312; PaCO2, 62.8 mm Hg; PaO2,58.9 mm Hg; HCO3 concentration, 30.8 mmol/L; base excess, 3.2 mmol/L; and oxygen saturation, 90.4%. Finally, he required tracheal intubation and ventilation. After 6 weeks, the patient was transferred to a general ward, and the follow-up ABGA and end-tidal CO2 showed normal range with the discontinuation of pregabalin. We demonstrated CO2 retention via ABGA in a patient with SCI due to cervical myelopathy who developed hypercapnia after taking a therapeutic dose of pregabalin. Physicians should pay particular attention to CO2 retention when prescribing a therapeutic dosage of pregabalin in a patient with cervical SCI.