Factors associated with carbon dioxide transfer in an experimental model of severe acute kidney injury and hypoventilation during high bicarbonate continuous renal replacement therapy and oxygenation membrane support.

OBJECTIVE: To investigate the factors influencing carbon dioxide transfer in a system that integrates an oxygenation membrane in series with high-bicarbonate continuous veno-venous hemodialysis in hypercapnic animals. METHODS: In an experimental setting, we induced severe acute kidney injury and hypercapnia in five female Landrace pigs. Subsequently, we initiated high (40mEq/L) bicarbonate continuous veno-venous hemodialysis with an oxygenation membrane in series to maintain a pH above 7.25. At intervals of 1 hour, 6 hours, and 12 hours following the initiation of continuous veno-venous hemodialysis, we performed standardized sweep gas flow titration to quantify carbon dioxide transfer. We evaluated factors associated with carbon dioxide transfer through the membrane lung with a mixed linear model. RESULTS: A total of 20 sweep gas flow titration procedures were conducted, yielding 84 measurements of carbon dioxide transfer. Multivariate analysis revealed associations among the following (coefficients ± standard errors): core temperature (+7.8 ± 1.6 °C, p < 0.001), premembrane partial pressure of carbon dioxide (+0.2 ± 0.1/mmHg, p < 0.001), hemoglobin level (+3.5 ± 0.6/g/dL, p < 0.001), sweep gas flow (+6.2 ± 0.2/L/minute, p < 0.001), and arterial oxygen saturation (-0.5 ± 0.2%, p = 0.019). Among these variables, and within the physiological ranges evaluated, sweep gas flow was the primary modifiable factor influencing the efficacy of low-blood-flow carbon dioxide removal. CONCLUSION: Sweep gas flow is the main carbon dioxide removal-related variable during continuous veno-venous hemodialysis with a high bicarbonate level coupled with an oxygenator. Other carbon dioxide transfer modulating variables included the hemoglobin level, arterial oxygen saturation, partial pressure of carbon dioxide and core temperature. These results should be interpreted as exploratory to inform other well-designed experimental or clinical studies.

Ethanol's disruptive effects upon early breathing plasticity and blood parameters associated with hypoxia and hypercapnia.

Early ethanol exposure affects respiratory neuroplasticity; a risk factor associated with the Sudden Infant Death Syndrome. High and chronic ethanol doses exert long-lasting effects upon respiratory rates, apneic episodes and ventilatory processes triggered by hypoxia. The present study was performed in 3-9-day-old rat pups. Respiratory processes under normoxic and hypoxic conditions were analyzed in pups intoxicated with different ethanol doses which were pre-exposed or not to the drug. A second major goal was to examine if acute and/or chronic early ethanol exposure affects blood parameters related with hypercapnic or hypoxic states. In Experiment 1, at postnatal day 9, animals previously treated with ethanol (2.0 g/kg) or vehicle (0.0 g/kg) were tested sober or intoxicated with 0.75, 1.37 or 2.00 g/kg ethanol. The test involved sequential air conditions defined as initial normoxia, hypoxia and recovery normoxia. Motor activity was also evaluated. In Experiment 2, blood parameters indicative of possible hypoxic and hypercapnic states were assessed as a function of early chronic or acute experiences with the drug. The main results of Experiment 1 were as follows: i) ethanol's depressant effects upon respiratory rates increased as a function of sequential treatment with the drug (sensitization); ii) ethanol inhibited apneic episodes even when employing the lowest dose at test (0.75 g/kg); iii) the hyperventilatory response caused by hypoxia negatively correlated with the ethanol dose administered at test; iv) ventilatory long-term facilitation (LTF) during recovery normoxia was observed in pups pre-exposed to the drug and in pups that received the different ethanol doses at test; v) self-grooming increased in pups treated with either 1.37 or 2.00 g/kg ethanol. The main result of Experiment 2 indicated that acute as well as chronic ethanol exposure results in acidosis-hypercapnia. The results indicate that early and brief experiences with ethanol are sufficient to affect different respiratory plasticity processes as well as blood biomarkers indicative of acidosis-hypercapnia. An association between the LTF process and the acidosis-hypercapnic state caused by ethanol seems to exist. The mentioned experiences with the drug are sufficient to result in an anomalous programming of respiratory patterns and metabolic conditions.

End-tidal CO2 and transcutaneous CO2 : Are we ready to replace arterial CO2 in awake children?

INTRODUCTION: Arterial blood gas analysis (ABG) is the gold standard test for carbon dioxide measurement. End-tidal PCO2 (PetCO2 ) and transcutaneous PCO2 (PtcCO2 ) are noninvasive alternative methods. OBJECTIVE: To examine the use of PetCO2 and PtcCO2 as PaCO2 surrogates in awake children. METHODS: A prospective observational study. Consecutive awake children in a stable condition referred to the Sleep Unit of Hospital de Pediatría Dr. J. P. Garrahan with suspected or confirmed sleep-related respiratory disorders requiring ABG were included. PetCO2 and PtcCO2 were recorded simultaneously during arterial puncture. PetCO2 and PtCO2 values were compared with PaCO2 . Correlation coefficient and Bland-Altman analysis were applied. The sample size was calculated considering a mean difference ≤3 mmHg as clinically acceptable. RESULTS: Sixty-eight sample sets were obtained from 67 patients. The median age was 9.11 years (0.23-18.76). During 94.1% of the procedures patients breathed spontaneously, 30% needed multiple punctures and 92% resulted in pain. Median (IQR) PaCO2 (mmHg) was 36.3 (31.45; 40.90), PetCO2 33.0 (29; 39) and PtcCO2 38.8 (32.95; 43.32). Correlation and agreement for PaCO2 /PetCO2 and PaCO2 /PtcCO2 was r = .6 and .9, and media of bias = 2.83 (-9.97; 15.64) and -1.88 (-9.01; 5.24), respectively. Hypercapnia (PaCO2 > 45.0 mmHg) was present in 8/68 (11.8%) samples. Sensitivity, specificity, positive predictive value and negative predictive value to detect hypercapnia with PetCO2 was 38%, 98%, 75%, and 92%, respectively, and with PtcCO2 , 100%, 90%, 57%, and 100%, respectively. CONCLUSION: PtcCO2 showed better agreement with PaCO2 than PetCO2 but because of the wide dispersion of values, neither method can replace the gold standard. Transcutaneous CO2 might be a good screening tool to detect hypercapnia in awake children.

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES: Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. METHODS: CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. RESULTS: Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). CONCLUSIONS: Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS.

Effects of chronic sleep fragmentation on wake-active neurons and the hypercapnic arousal response.

STUDY OBJECTIVES: Delayed hypercapnic arousals may occur in obstructive sleep apnea. The impaired arousal response is expected to promote more pronounced oxyhemoglobin desaturations. We hypothesized that long-term sleep fragmentation (SF) results in injury to or dysfunction of wake-active neurons that manifests, in part, as a delayed hypercapnic arousal response. DESIGN: Adult male mice were implanted for behavioral state recordings and randomly assigned to 4 weeks of either orbital platform SF (SF4wk, 30 events/h) or control conditions (Ct4wk) prior to behavioral, histological, and locus coeruleus (LC) whole cell electrophysiological evaluations. MEASUREMENTS AND RESULTS: SF was successfully achieved across the 4 week study, as evidenced by a persistently increased arousal index, P < 0.01 and shortened sleep bouts, P < 0.05, while total sleep/wake times and plasma corticosterone levels were unaffected. A multiple sleep latency test performed at the onset of the dark period showed a reduced latency to sleep in SF4wk mice (P < 0.05). The hypercapnic arousal latency was increased, Ct4wk 64 ± 5 sec vs. SF4wk 154 ± 6 sec, P < 0.001, and remained elevated after a 2 week recovery (101 ± 4 sec, P < 0.001). C-fos activation in noradrenergic, orexinergic, histaminergic, and cholinergic wake-active neurons was reduced in response to hypercapnia (P < 0.05-0.001). Catecholaminergic and orexinergic projections into the cingulate cortex were also reduced in SF4wk (P < 0.01). In addition, SF4wk resulted in impaired LC neuron excitability (P < 0.01). CONCLUSIONS: Four weeks of sleep fragmentation (SF4wk) impairs arousal responses to hypercapnia, reduces wake neuron projections and locus coeruleus neuronal excitability, supporting the concepts that some effects of sleep fragmentation may contribute to impaired arousal responses in sleep apnea, which may not reverse immediately with therapy.

[Analysis of factors associated with chronic hypercapnia in patients with myotonic dystrophy]. / Análisis de factores relacionados con hipercapnia crónica en la distrofia miotónica.

Myotonic dystrophy (DM) is the most common dystrophy in adults. Several factors may explain the chronic CO2 retention. The selection of patients, different clinical stages and evaluation forms may explain the differing results obtained. Our objectives were to characterize respiratory function and to evaluate factors associated with chronic retention of CO2 in DM. We included 27 consecutive ambulatory and stable patients who were allocated into normocapnic and hypercapnic groups (PaCO2 ≥ 43 mmHg). Forced vital capacity (FVC), maximum static pressure, voluntary apnea time, Epworth scale and arterial blood gases were measured. The CO2 chemosensitivity was assessed using CO2 rebreathing (Read method). The slope ΔP0.1/ΔPCO2 expressed the CO2 chemosensitivity. A 59.3% (16/27) presented hypercapnia. FVC and respiratory muscle strength were normal or showed mild to moderate decrease. No significant differences in these variables were found in both groups. Inadequate response to CO2 (slope ΔP0.1/ΔPCO2 low (< 0.1 cm H2O/mmHg) or flat) was associated with hypercapnia (p < 0.005). Chronic retention of CO2 represented 11.56 times higher risk of inadequate response to CO2. The group with low-flat slope ΔP0.1/ΔPCO2 showed higher PaCO2 (p = 0.0017) and more prolonged voluntary apnea time (p = 0.002). We conclude that in our patients with DM, chronic CO2 retention was associated with the presence of abnormalities of the central control of breathing. Our results allow explaining previous reports describing the striking frequency of postoperative respiratory failure and difficulties in the process of weaning from mechanical ventilation.

Análisis de factores relacionados con hipercapnia crónica en la distrofia miotónica / Analysis of factors associated with chronic hypercapnia in patients with myotonic dystrophy

La distrofia miotónica (DM) es la distrofia muscular más común en adultos. Diversos factores pueden explicar la retención crónica de CO2. La selección de pacientes, diferentes estadios evolutivos y formas de evaluación, pueden explicar los resultados disímiles al respecto. Nuestros objetivos fueron caracterizar la función respiratoria y analizar los factores relacionados con la retención crónica de CO2 en la DM. Se incluyeron 27 pacientes ambulatorios consecutivos, estables clínicamente y se los agrupó como normocápnicos e hipercápnicos (PaCO2 ≥ 43 mm Hg). Se determinaron capacidad vital forzada (FVC), presiones estáticas máximas, tiempo de apnea voluntaria, escala de Epworth y gases arteriales. La quimiosensibilidad al CO2 se evaluó mediante la reinhalación de CO2 (método de Read). La pendiente ∆P0.1/∆PCO2 expresa la quimiosensibilidad al CO2. El 59.3% tenían hipercapnia. La FVC y la fuerza muscular respiratoria fueron normales o mostraron disminución leve a moderada, sin diferencias significativas en ambos grupos. La inadecuada respuesta al CO2 (pendientes ∆P0.1/∆PCO2 bajas (< 0.1 cmH2O/mm Hg) o planas) se asoció con hipercapnia (p < 0.005) y ésta significó un riesgo 11.6 veces mayor de inadecuada respuesta al CO2. El grupo con pendiente ∆P0.1/∆PCO2 baja-plana mostró mayor PaCO2 (p = 0.0017) y tiempo de apnea voluntaria más prolongado (p = 0.002). Concluimos que, en nuestros pacientes con DM, la hipercapnia crónica se asoció a la presencia de anomalías del control central de la respiración. Estos resultados permiten explicar los informes previos que describen la llamativa ocurrencia de insuficiencia respiratoria postoperatoria y las dificultades en el proceso de desvinculación de asistencia ventilatoria mecánica en estos pacientes.

Myotonic dystrophy (DM) is the most common dystrophy in adults. Several factors may explain the chronic CO2 retention. The selection of patients, different clinical stages and evaluation forms may explain the differing results obtained. Our objectives were to characterize respiratory function and to evaluate factors associated with chronic retention of CO2 in DM. We included 27 consecutive ambulatory and stable patients who were allocated into normocapnic and hypercapnic groups (PaCO2 ≥ 43 mmHg). Forced vital capacity (FVC), maximum static pressure, voluntary apnea time, Epworth scale and arterial blood gases were measured. The CO2 chemosensitivity was assessed using CO2 rebreathing (Read method). The slope ΔP0.1/ΔPCO2 expressed the CO2 chemosensitivity. A 59.3% (16/27) presented hypercapnia. FVC and respiratory muscle strength were normal or showed mild to moderate decrease. No significant differences in these variables were found in both groups. Inadequate response to CO2 (slope ΔP0.1/ΔPCO2 low (< 0.1 cm H2O/mmHg) or flat) was associated with hypercapnia (p < 0.005). Chronic retention of CO2 represented 11.56 times higher risk of inadequate response to CO2. The group with low-flat slope ΔP0.1/ΔPCO2 showed higher PaCO2 (p = 0.0017) and more prolonged voluntary apnea time (p = 0.002). We conclude that in our patients with DM, chronic CO2 retention was associated with the presence of abnormalities of the central control of breathing. Our results allow explaining previous reports describing the striking frequency of postoperative respiratory failure and difficulties in the process of weaning from mechanical ventilation.

Análisis de factores relacionados con hipercapnia crónica en la distrofia miotónica / Analysis of factors associated with chronic hypercapnia in patients with myotonic dystrophy

La distrofia miotónica (DM) es la distrofia muscular más común en adultos. Diversos factores pueden explicar la retención crónica de CO2. La selección de pacientes, diferentes estadios evolutivos y formas de evaluación, pueden explicar los resultados disímiles al respecto. Nuestros objetivos fueron caracterizar la función respiratoria y analizar los factores relacionados con la retención crónica de CO2 en la DM. Se incluyeron 27 pacientes ambulatorios consecutivos, estables clínicamente y se los agrupó como normocápnicos e hipercápnicos (PaCO2 ≥ 43 mm Hg). Se determinaron capacidad vital forzada (FVC), presiones estáticas máximas, tiempo de apnea voluntaria, escala de Epworth y gases arteriales. La quimiosensibilidad al CO2 se evaluó mediante la reinhalación de CO2 (método de Read). La pendiente ∆P0.1/∆PCO2 expresa la quimiosensibilidad al CO2. El 59.3% tenían hipercapnia. La FVC y la fuerza muscular respiratoria fueron normales o mostraron disminución leve a moderada, sin diferencias significativas en ambos grupos. La inadecuada respuesta al CO2 (pendientes ∆P0.1/∆PCO2 bajas (< 0.1 cmH2O/mm Hg) o planas) se asoció con hipercapnia (p < 0.005) y ésta significó un riesgo 11.6 veces mayor de inadecuada respuesta al CO2. El grupo con pendiente ∆P0.1/∆PCO2 baja-plana mostró mayor PaCO2 (p = 0.0017) y tiempo de apnea voluntaria más prolongado (p = 0.002). Concluimos que, en nuestros pacientes con DM, la hipercapnia crónica se asoció a la presencia de anomalías del control central de la respiración. Estos resultados permiten explicar los informes previos que describen la llamativa ocurrencia de insuficiencia respiratoria postoperatoria y las dificultades en el proceso de desvinculación de asistencia ventilatoria mecánica en estos pacientes.(AU)

Myotonic dystrophy (DM) is the most common dystrophy in adults. Several factors may explain the chronic CO2 retention. The selection of patients, different clinical stages and evaluation forms may explain the differing results obtained. Our objectives were to characterize respiratory function and to evaluate factors associated with chronic retention of CO2 in DM. We included 27 consecutive ambulatory and stable patients who were allocated into normocapnic and hypercapnic groups (PaCO2 ≥ 43 mmHg). Forced vital capacity (FVC), maximum static pressure, voluntary apnea time, Epworth scale and arterial blood gases were measured. The CO2 chemosensitivity was assessed using CO2 rebreathing (Read method). The slope ΔP0.1/ΔPCO2 expressed the CO2 chemosensitivity. A 59.3% (16/27) presented hypercapnia. FVC and respiratory muscle strength were normal or showed mild to moderate decrease. No significant differences in these variables were found in both groups. Inadequate response to CO2 (slope ΔP0.1/ΔPCO2 low (< 0.1 cm H2O/mmHg) or flat) was associated with hypercapnia (p < 0.005). Chronic retention of CO2 represented 11.56 times higher risk of inadequate response to CO2. The group with low-flat slope ΔP0.1/ΔPCO2 showed higher PaCO2 (p = 0.0017) and more prolonged voluntary apnea time (p = 0.002). We conclude that in our patients with DM, chronic CO2 retention was associated with the presence of abnormalities of the central control of breathing. Our results allow explaining previous reports describing the striking frequency of postoperative respiratory failure and difficulties in the process of weaning from mechanical ventilation.(AU)

Effects of the recombinant form of the natural human B-type natriuretic peptide and levosimendan on pulmonary hyperventilation and chemosensivity in heart failure.

BACKGROUND: The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of natriuretic peptides in clinical conditions associated with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains unexplored. METHODS: We tested in a prospective, placebo-controlled, three-way cross-over, double-blind randomized study the effects of the recombinant form of the natural human B-type natriuretic peptide (R-BNP) in comparison with placebo and levosimendan on chemoreflex sensitivity at rest, as well as their effects on pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity both at rest and during exercise. RESULTS: Eleven stable chronic HF patients were randomized to sessions of 6-min treadmill-walking tests during placebo, or levosimendan or R-BNP intravenous infusion in the following conditions: room air, hypoxia, and hypercapnia. R-BNP administration determined higher pulmonary ventilatory response at rest and during exercise (P < 0.001) consequent to a boost of respiratory rate (P < 0.001) under room air and hypoxia conditions. Norepinephrine blood levels increased from rest to exercise in all conditions without differences among placebo, levosimendan, and R-BNP effects. BNP blood levels remained unchanged. CONCLUSIONS: The novelty of the present findings is that R-BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise.

Análisis de factores relacionados con hipercapnia crónica en la distrofia miotónica. / [Analysis of factors associated with chronic hypercapnia in patients with myotonic dystrophy].

Myotonic dystrophy (DM) is the most common dystrophy in adults. Several factors may explain the chronic CO2 retention. The selection of patients, different clinical stages and evaluation forms may explain the differing results obtained. Our objectives were to characterize respiratory function and to evaluate factors associated with chronic retention of CO2 in DM. We included 27 consecutive ambulatory and stable patients who were allocated into normocapnic and hypercapnic groups (PaCO2 ÔëÑ 43 mmHg). Forced vital capacity (FVC), maximum static pressure, voluntary apnea time, Epworth scale and arterial blood gases were measured. The CO2 chemosensitivity was assessed using CO2 rebreathing (Read method). The slope ÎöP0.1/ÎöPCO2 expressed the CO2 chemosensitivity. A 59.3

(16/27) presented hypercapnia. FVC and respiratory muscle strength were normal or showed mild to moderate decrease. No significant differences in these variables were found in both groups. Inadequate response to CO2 (slope ÎöP0.1/ÎöPCO2 low (< 0.1 cm H2O/mmHg) or flat) was associated with hypercapnia (p < 0.005). Chronic retention of CO2 represented 11.56 times higher risk of inadequate response to CO2. The group with low-flat slope ÎöP0.1/ÎöPCO2 showed higher PaCO2 (p = 0.0017) and more prolonged voluntary apnea time (p = 0.002). We conclude that in our patients with DM, chronic CO2 retention was associated with the presence of abnormalities of the central control of breathing. Our results allow explaining previous reports describing the striking frequency of postoperative respiratory failure and difficulties in the process of weaning from mechanical ventilation.

[Salbutamol improves diaphragmatic contractility in chronic airway obstruction]. / El salbutamol mejora la contractilidad diafragmática en la obstrucción crónica de la vía aérea.

INTRODUCTION: Chronic airflow obstruction in conditions such as chronic obstructive pulmonary disease is associated with respiratory muscle dysfunction. Our aim was to study the effects of salbutamol-a beta-adrenergic agonist known to improve muscle strength in physiologic and pathologic conditions-on diaphragm contractility in an animal model of chronic airway obstruction achieved by tracheal banding. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were randomized into a control group and 3 tracheal banding groups, 1 that received acute salbutamol treatment, 1 that received chronic salbutamol treatment, and 1 that received nothing. Arterial blood gases, acid-base balance, and in vitro diaphragmatic contractility were evaluated by measuring peak twitch tension, contraction time, contraction velocity, half-relaxation time, relaxation velocity, and force-frequency curves. RESULTS: The 3 study groups had significantly reduced arterial pH and increased PaCO2 and bicarbonate levels compared to the control group (P<.05). The untreated tracheal banding group had significantly reduced peak twitch tension and contraction velocity, and a significantly lower force-frequency curve in comparison with the other groups (P<.05). The chronic treatment group had a higher relaxation velocity than the untreated study group (P<.05). The mean (SE) peak twitch tension values were 6.46 (0.90)N/cm(2) for the control group, 3.28 (0.55)N/cm(2) for the untreated tracheal banding group, 6.18 (0.71)N/cm(2) for the acute treatment group, and 7.09 (0.59)N/cm(2) for the chronic treatment group. CONCLUSIONS: Diaphragmatic dysfunction associated with chronic airflow obstruction improves with both the acute and chronic administration of salbutamol. The mechanisms involved in respiratory muscle dysfunction warrant further study.

Urinary bladder partial carbon dioxide tension during hemorrhagic shock and reperfusion: an observational study.

INTRODUCTION: Continuous monitoring of bladder partial carbon dioxide tension (PCO2) using fibreoptic sensor technology may represent a useful means by which tissue perfusion may be monitored. In addition, its changes might parallel tonometric gut PCO2. Our hypothesis was that bladder PCO2, measured using saline tonometry, will be similar to ileal PCO2 during ischaemia and reperfusion. METHOD: Six anaesthetized and mechanically ventilated sheep were bled to a mean arterial blood pressure of 40 mmHg for 30 min (ischaemia). Then, blood was reinfused and measurements were repeated at 30 and 60 min (reperfusion). We measured systemic and gut oxygen delivery and consumption, lactate and various PCO2 gradients (urinary bladder-arterial, ileal-arterial, mixed venous-arterial and mesenteric venous-arterial). Both bladder and ileal PCO2 were measured using saline tonometry. RESULTS: After bleeding systemic and intestinal oxygen supply dependency and lactic acidosis ensued, along with elevations in PCO2 gradients when compared with baseline values (all values in mmHg; bladder DeltaPCO2 3 +/- 3 versus 12 +/- 5, ileal DeltaPCO2 9 +/- 5 versus 29 +/- 16, mixed venous-arterial PCO2 5 +/- 1 versus 13 +/- 4, and mesenteric venous-arterial PCO2 4 +/- 2 versus 14 +/- 4; P < 0.05 versus basal for all). After blood reinfusion, PCO2 gradients returned to basal values except for bladder DeltaPCO2, which remained at ischaemic levels (13 +/- 7 mmHg). CONCLUSION: Tissue and venous hypercapnia are ubiquitous events during low flow states. Tonometric bladder PCO2 might be a useful indicator of tissue hypoperfusion. In addition, the observed persistence of bladder hypercapnia after blood reinfusion may identify a territory that is more susceptible to reperfusion injury. The greatest increase in PCO2 gradients occurred in gut mucosa. Moreover, the fact that ileal DeltaPCO2 was greater than the mesenteric venous-arterial PCO2 suggests that tonometrically measured PCO2 reflects mucosal rather than transmural PCO2. Ileal DeltaPCO2 appears to be the more sensitive marker of ischaemia.

Subarachnoid hemorrhage following permissive hypercapnia in a patient with severe acute asthma.

In this article, we describe a case of a subarachnoid hemorrhage (SAH) in an acute severe asthma patient following mechanical hypoventilation. A 49-year-old man was admitted to an Intensive Care Unit with an acute exacerbation of asthma. After 3 days of mechanical ventilation (hypercapnia and normoxaemia), it was noted that his right pupil was fixed, dilated, and unreactive to light. Computed tomography (CT) scan showed localized SAH within the basilar cisterns and diffuse cerebral swelling. On the fourth day, a new CT scan showed hemorrhage resorption and a cerebral swelling decrease. In the following days, the patient's condition continued improving with no detectable neurological deficits. A review of similar published reports showed that all patients performed respiratory acidosis, normoxaemia, and hypercapnia. The most frequent neurological sign was mydriasis, and all subjects showed cerebral edema. Since normoxaemic hypercapnia has been associated with absence, or less cerebral edema, we considered additional factors to explain cerebral edema and intracranial hypertension causes. Thus, intrathoracic pressures due to patient's efforts by forcibly exhaling, or during mechanical ventilation, would further increase intracranial pressure by limiting cerebral venous drainage. This case emphasizes the fact that patients with acute severe asthma who have developed profoundly hypercarbic without hypoxia before or during mechanical ventilation, may have raised critical intracranial pressure.

La fosfatidilcolina induce un aumento en la producción de interleucina-6 y mejora la sobrevida de ratas con sepsis neonatal por Klebsiella pneumoniae / Phosphatidylcholine induces and increase of inleukin-6 production and improves life span of rats with neonatal infection by Klebsiella pneumoniae

Las infecciones por bacterias gram negativas son una de las primeras causas de muerte en el recién nacido. La depuración de bacterias es deficiente en el neonato, situación que aumenta la susceptibilidad a las infecciones. En este estudio se logró mejorar el patrón de depuración de Klebsiella pneumoniae en ratas wistar recién nacidas inoculadas por vía IP con 800mg/k de fosfatidilcolina de soya (FC), en contraste con el grupo testigo inyectado con PBS(p<0.05). La sobrevida de los animales aumentó (p<0.05), y los cambios leucocitarios se caracterizaron por una mayor leucocitosis y neutrofilia durante el pico de bacteremia en los animales tratados con FC. Los niveles circulantes de interleucina-6 fueron mayores en el grupo de FC, observándose además hematopoyesis extramedular de las series granulocíticas (p<0.05) y de megacariocitos (p<0.01) en el bazo de las ratas del grupo de FC. No se observaron cambios significativos en los depósitos de granulocitos en la médula ósea de ambos grupos. La mejoría de la sobrevida, los cambios leucocitarios y los focos de hematopoyesis extramedular, parecen asociarse al aumento en la producción de IL-6. Los resultados sugieren que la IL-6 participa en el mecanismo de protección; y que la FC induce en este modelo a septicemia experimental. La FC parece comportarse como un inmunomodulador inespecífico de la respuesta aguda a la infección bacteriana

Central chemoreceptor drive to breathing in unanesthetized toads, Bufo paracnemis.

Central chemoreceptor drive to breathing was studied in unanesthetized toads, equipped with face masks to measure pulmonary ventilation and arterial catheters to analyze blood gases. Two series of experiments were performed. Expt. 1: The fourth cerebral ventricle was perfused with solutions of mock CSF, adjusted to stepwise decreasing pH values. Concomitant perfusion-induced increases of pulmonary ventilation, pHa and PaO2 were measured. Expt. 2: Inspiration of hypercapnic gas mixtures was applied to stimulate both central and peripheral chemoreceptors. Subsequently, only peripheral chemoreceptors were stimulated. This was accomplished by repeating the hypercapnic conditions while the fourth ventricle was perfused with mock CSF at pH 7.7. This procedure reduced the slope of the ventilatory response curve by about 80%. Taken together, the experiments suggest a highly dominant role of central chemoreceptors in the ventilatory acid-base regulation of the toad.