Episodes Of Hypercapnia Research Articles

A Retrospective Cohort Study of the Impact of Implementing Volume-Targeted Compared to Pressure-Limited Ventilation in a Single-Center, Level III Neonatal Intensive Care Unit in Oman.

Background The use of volume-targeted ventilation (VTV) in neonatology has been introduced in the last decade. This study was performed to determine the impact of clinical implementation of volume-targeted conventional mechanical ventilation using the volume guarantee mode in mechanical ventilation of all neonates needing mechanical ventilation compared to pressure-limited ventilation (PLV) modes. The mortality rate, duration of mechanical ventilation, and bronchopulmonary dysplasia were the primary outcomes of the study. Methodology This retrospective cohort study was conducted at a level III-VI neonatal intensive care unit (NICU) within a tertiary academic hospital in Oman. All intubated neonates admitted to the NICU within two time periods, i.e., the PLV cohort: January 2011 to December 2013 (three years), and the VTV cohort: January 2017 to December 2019 (three years), were eligible for inclusion in the study. Neonates were excluded if they had multiple congenital anomalies, tracheostomy, and those with a Do Not Resuscitate status. A predetermined data set was collected retrospectively from electronic records. The PLV and VTV cohorts were compared, and SPSS version 25 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results A total of 290 neonates were included (PLV: n = 138, and VTV: n = 152). The two cohorts were statistically similar in their baseline characteristics, including gestational age, birth weight, Apgar scores, indications for mechanical ventilation, age at intubation, need for surfactant therapy, and age at extubation. The VTV cohort had a significantly lower mortality rate (n (%) = 10 (6.6%) vs. 21 (15.3%), p = 0.02). An insignificant trend of lower duration of ventilation was observed in the VTV cohort (34.5 vs. 50.5 hours, p = 0.24). There was no significant difference in bronchopulmonary dysplasia (16 (21.3%) vs. 12 (17.8%), p = 0.18). VTV was associated with a significant reduction in pulmonary hemorrhage (1 (0.7%) vs. 8 (5.7%), p = 0.04), episodes of hypocapnia (2 vs. 3/patient, p = 0.04), and episodes of hypercapnia (0 vs 1/patient, p = 0.04). Conclusions The implementation of VTV in clinical practice in our level III-VI NICU was associated withsignificant advantages, including reduction in mortality, pulmonary hemorrhage, and episodes of hypercapnia and hypocapnia. A large prospective, randomized, and multicenter trial is recommended to confirm these findings.

VOLUMETRIC CAPNOGRAPHY FOR RESPIRATORY MONITORING OF PATIENTS DURING ROUTINE COLONOSCOPY WITH ROOM-AIR AND CARBON DIOXIDE INSUFFLATION.

Capnography and carbon dioxide (CO2) insufflation during gastrointestinal endoscopy under sedation are associated with safety and comfort improvements, respectively. Capnography can provide early detection of apnea and hypoxemia, whereas CO2 insufflation causes lower periprocedural discomfort. This is the first study to report the application of volumetric capnography in colonoscopy. This study aimed to evaluate the use of volumetric capnography with room air (RA) and CO2 insufflation during routine colonoscopy. In this prospective cohort study, 101 patients who underwent routine colonoscopy under sedation with volumetric capnography monitoring were included. Insufflation with RA was used to distend the intestinal lumen in group 1 (n=51), while group 2 (n=50) used CO2 insufflation. The primary endpoints were episodes of hypoxia, alveolar hypoventilation, and end-tidal CO2 (EtCO2). The secondary endpoints were tidal volume per minute, consumption of sedation medications, and post-procedure pain using the Gloucester modified pain scale. The number of episodes of hypoxia (SpO2<90%) was similar between the groups: four episodes in Group 1 and two episodes in Group 2. The duration of hypoxia was significantly longer in group 2 (P=0.02). Hypoalveolar ventilation (EtCO2) occurred more frequently in Group 2 than in Group 1 (27 vs 18 episodes, P=0.05). Regarding EtCO2, Group 2 showed higher values in cecal evaluation (28.94±4.68 mmHg vs 26.65±6.12 mmHg, P=0.04). Regarding tidal volume per minute, Group 2 had significantly lower values at the cecal interval compared to Group 1 (2027.53±2818.89 vs 970.88±1840.25 L/min, P=0.009). No episodes of hypercapnia (EtCO2 > 60 mmHg) occurred during the study. There was no difference in the consumption of sedation medications between the groups. Immediately after colonoscopy, Group 2 reported significantly less pain than Group 1 (P=0.05). In our study, volumetric capnography during colonoscopy was feasible and effective for monitoring ventilatory parameters and detecting respiratory complications. CO2 insufflation was safe and associated with less pain immediately after colonoscopy.

Blockade of alpha2-adrenergic receptors in the caudal raphe region enhances the renal sympathetic nerve activity response to acute intermittent hypercapnia in rats.

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.

Patients of risk groups in the perioperative period: the review of modern guidelines

Background. According to the Decree of the Ministry of Health of Ukraine № 275 issued on 11.09.2018, there is a list of measures to ensure surgical safety and patient’s safety. These measures can be divided into those that should be performed 1) before anesthesia; 2) before skin dissection; 3) before the patient leaves the operating room. Perioperative medicine (POM) is a patient-centered and interdisciplinary perioperative care for surgical patients.&#x0D; Objective. To describe the current recommendations for POM.&#x0D; Materials and methods. Review of available guidance documents.&#x0D; Results and discussion. The pathophysiology of postoperative complications (infectious processes, intestinal paralysis, respiratory failure, kidney damage, etc.) includes the following factors: triggers (anxiety, pain, surgical trauma), patient factors (age, comorbid conditions), the consequences of general operative stress (autonomous system imbalance, inflammation, coagulopathy, metabolic imbalance). Clinical evaluation or biomarkers should be used to identify high-risk patients in the perioperative period. Measures to improve postoperative rehabilitation should be carried out in the pre-, intra- and postoperative period. Thus, in the preoperative period it is necessary to examine the patient, to provide the carbohydrate load 2 hours before the intervention, to conduct antibiotic prophylaxis, to correct or stabilize the comorbid diseases (especially cardiovascular and renal diseases, diabetes, anemia). In the intraoperative period it is necessary to maintain normovolemia and normothermia, to use protective mechanical lung ventilation, to limit the use of opioids, to perform extubation immediately after the intervention. In the postoperative period early activation, early enteral nutrition and early removal of drainages and catheters should be used. The key components of POM include the identification of low-risk patients in order to save resources, the identification of high-risk patients with the possible use of alternative management strategies, and the frequent risk reassessment. The main components of the success of anesthesia include preoperative assessment of the patient’s somatic status and risk, use of controlled hypnotics and effective and predictable muscle relaxant, use of analgesics that break down quickly and have no ability to accumulate, control of the hemodynamics stability, blood gases and acid-base balance. To prevent the perioperative myocardial ischemia, it is advisable to use esmolol – a cardioselective β-blocker of ultrashort action. Preoperative anxiety, intubation and extubation, surgical manipulations lead to the excessive adrenergic response, which justifies the use of β-blockers. The pharmacological effects of esmolol (Biblok, “Yuria-Pharm”) include the reduction of myocardial oxygen consumption, increase of the diastole duration, limitation of the free radicals’ production, control of the activity of metalloproteinases, and the reduction of inflammation around atherosclerotic plaques. In addition, esmolol (Biblok) is able to reduce intra- and postoperative use of opioids, and therefore its use as a component of multimodal total intravenous anesthesia has been proposed. Preoperative administration of esmolol may also be an effective and safe method of myocardial protection in patients undergoing cardiac surgery. β-blockers are well tolerated in patients with acute hypovolaemia during anesthesia, however, episodes of hypercapnia should be avoided during their use.&#x0D; Conclusions. 1. For the optimal POM, the individual risk of perioperative complications should be determined. 2. POM includes a number of pre-, intra- and postoperative measures. 3. The use of ultrashort-acting β-blocker esmolol prevents intraoperative myocardial ischemia, has antioxidant and anti-inflammatory effects, reduces the need for opioids.

Hyperoxia blunts renal sympathetic nerve activity response to acute intermittent hypercapnia in rats.

Activation of the sympathetic nervous system plays an important role in the pathophysiology of sleep-related breathing disorders. The aim of the present study was to examine the effects of different levels of hypercapnia in the presence of various background oxygen levels on the magnitude of sympathoexcitation, measured by the renal sympathetic nerve activity (RSNA) in the acute intermittent hypercapnia (AIHc) rat model. The study was conducted on 56 urethane-anesthetized, vagotomized and mechanically ventilated Sprague-Dawley rats (n = 7/group). Each experimental group was subjected to a distinct AIHc protocol that varied in the applied levels of hypercapnia and background oxygen. Mean arterial pressure and RSNA were analyzed in 7 experimental time points: baseline, five hypercapnic episodes (each lasting 3 min) and 15 minutes following the last hypercapnic episode. Exposure to severe hypercapnia (FiCO2 = 0.15) evoked an increase in RSNA, which was preserved throughout the protocol, whereas in moderate hypercapnia (FiCO2 = 0.05) groups there was a trend of progressive diminution of RSNA magnitude following the first hypercapnic episode. Exposure to severe hypercapnia elicited significantly greater RSNA response during first hypercapnic episode and it was enhanced during subsequent episodes compared to exposure to moderate hypercapnia. Additionally, hyperoxic2 background (50% O2) blunted the RSNA response to AIHc compared to room air background, both in severe and moderate hypercapnia groups. Mean arterial blood pressure was preserved throughout the experimental protocol in all studied groups. These findings indicate that acute intermittent hypercapnia evokes increased renal sympathetic nerve activity that is dependent on the severity of hypercapnic exposures and the background oxygen level.

Improper monitoring and deviations from physiologic treatment goals in patients with brain injury in the early phases of emergency care

Severe traumatic brain injury (TBI), out-of-hospital cardiac arrest (OHCA) and intracerebral- and subarachnoid hemorrhage (ICH/SAH) are conditions associated with high mortality and morbidity. The aim of this study was to investigate the feasibility of obtaining continuous physiologic data and to identify possible harmful physiological deviations in these patients, in the early phases of emergency care. Patients with ICH/SAH, OHCA and severe TBI treated by the Physician-staffed Emergency Medical Service (P-EMS) between September and December 2016 were included. Physiological data were obtained from site of injury/illness, during transport, in the emergency department (ED) and until 3 h after admittance to the intensive care unit. Physiological deviations were based on predefined target values within each 5-min interval. 13 patients were included in the study, of which 38% survived. All patients experienced one or more episodes of hypoxia, 38% experienced episodes of hypercapnia and 46% experienced episodes of hypotension. The mean proportion of time without any monitoring in the pre-hospital phase was 29%, 47% and 56% for SpO2, end-tidal CO2 and systolic blood pressure, respectively. For the ED these proportions were 57%, 71% and 56%, respectively. Continuous physiological data was not possible to obtain in this study of critically ill and injured patients with brain injury. The patients had frequent deviations in blood pressure, SpO2 and end tidal CO2-levels, and measurements were frequently missing. There is a potential for improved monitoring as a tool for quality improvement in pre-hospital critical care.

Effects of chronic hypercapnia and elevated temperature on the immune response of the spiny lobster, Jasus lalandii

The West Coast rock lobster (WCRL), Jasus lalandii, inhabits highly variable environments frequented by upwelling events, episodes of hypercapnia and large temperature variations. Coupled with the predicted threat of ocean acidification and temperature change for the coming centuries, the immune response in this crustacean will most likely be affected. We therefore tested the hypothesis that chronic exposure to hypercapnia and elevated seawater temperature will alter immune function of the WCRL. The chronic effects of four combinations of two stressors (seawater pCO2 and temperature) on the total number of circulating haemocytes (THC) as well as on the lobsters’ ability to clear (inactivate) an injected dose of Vibrio anguillarum from haemolymph circulation were assessed. Juvenile lobsters were held in normocapnic (pH 8.01) or hypercapnic (pH 7.34) conditions at two temperatures (15.6 and 18.9 °C) for 48 weeks (n = 30 lobster per treatment), after which a subsample of lobsters (n = 8/treatment), all at a similar moult stage, were selected from each treatment for the immune challenge. Baseline levels of haemocytes (THC ml−1) and bacteria (CFU ml−1) in their haemolymph were quantified 24 h prior to bacterial challenge. Lobsters were then challenged by injecting 4 × 104V. anguillarum per g body weight directly into the cardiac region of each lobster and circulating haemocyte and culturable bacteria were measured at 20 min post challenge. No significant differences in THC ml−1 (p < 0.05) were observed between any of the treatment groups prior to the bacterial challenge. However lobsters chronically exposed to a combination of hypercapnia and low temperature had significantly higher (p < 0.05) THCs post-challenge in comparison with lobsters chronically exposed to hypercapnia and high temperature. A significant interactive effect was recorded between temperature and pH for the post-challenge THC data (two-way ANOVA, p = 0.0025). Lobster were very efficient at rendering an injected dose of bacteria non-culturable, with more than 83% of the theoretical challenge dose (∼1.7 × 105Vibrio ml−1 haemolymph) inactivated within the first 10 min following injection. Although differences in the inactivation of V. anguillarum were observed between treatment groups, none of these differences were significant. Clearance efficiency was in the following order: Hypercapnia/low temperature > normocapnia/high temperature > normocapnia/low temperature > hypercapnia/high temperature. This study demonstrated that despite chronic exposure to combinations of reduced seawater pH and high temperature, the WCRL was still capable of rapidly rendering an injected dose of bacteria non-culturable.

Phrenic long-term depression evoked by intermittent hypercapnia is modulated by serotonergic and adrenergic receptors in raphe nuclei.

Intermittent hypercapnia evokes prolonged depression of phrenic nerve activity (phrenic long-term depression, pLTD). This study was undertaken to investigate the role of 5-HT and α2-adrenergic receptors in the initiation of pLTD. Adult male urethane-anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to a protocol of acute intermittent hypercapnia (AIHc; 5 episodes of 15% CO2 in air, each episode lasting 3 min). The experimental group received microinjection of the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), the broad-spectrum 5-HT antagonist methysergide, or the α2-adrenergic antagonist yohimbine, whereas the control group received microinjection of 0.9% saline into the caudal raphe region. Peak phrenic nerve activity (pPNA) and burst frequency ( f) were analyzed during baseline (T0), during 5 hypercapnic episodes (THc1-THc5), and at 15, 30, and 60 min after the end of the last hypercapnic episode. In the control group, pPNA decreased 60 min after the end of the last hypercapnic episode compared with baseline values, i.e., pLTD developed ( P = 0.023). In the 8-OH-DPAT group, pPNA significantly decreased at T15, T30, and T60 compared with baseline values, i.e., pLTD developed ( P = 0.01). In the methysergide and yohimbine groups, AIHc did not evoke significant changes of the pPNA at T15, T30, and T60 compared with baseline values. In conclusion, activation of 5-HT1A receptors accentuated induction of pLTD, whereas blockade of α2-adrenergic receptors prevented development of pLTD following AIHc in anesthetized rats. These results suggest that chemical modulation of 5-HT and α2-adrenergic receptors in raphe nuclei affects hypercapnia-induced pLTD, offering important insights in understanding the mechanisms involved in development of respiratory plasticity. NEW & NOTEWORTHY Hypercapnia is a concomitant feature of many breathing disorders, including obstructive sleep apnea. In this study, acute intermittent hypercapnia evoked development of phrenic long-term depression (pLTD) 60 min after the last hypercapnic episode that was preserved if the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide was microinjected in the caudal raphe region before the hypercapnic stimulus. This study highlights that both 5-HT and adrenergic receptor activation is needed for induction of pLTD in urethane-anesthetized rats following intermittent hypercapnia exposure.

Intermittent hypercapnia-induced phrenic long-term depression is revealed after serotonin receptor blockade with methysergide in anaesthetized rats.

What is the central question of this study? Intermittent hypercapnia is a concomitant feature of breathing disorders. Hypercapnic stimuli evoke a form of respiratory plasticity known as phrenic long-term depression in experimental animals. This study was performed to investigate the putative role of serotonin receptors in the initiation of phrenic long-term depression in anaesthetized rats. What is the main finding and its importance? Phrenic nerve long-term depression was revealed in animals pretreated with the serotonin broad-spectrum antagonist, methysergide. This study highlights that serotonin receptors modulate respiratory plasticity evoked by acute intermittent hypercapnia in anaesthetized rats. This study was performed to test the hypothesis that intermittent hypercapnia can evoke a form of respiratory plasticity known as long-term depression of the phrenic nerve (pLTD) and that 5-HT receptors play a role in the initiation of pLTD. Adult male urethane-anaesthetized, vagotomized, paralysed, mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypercapnia protocol. One group received i.v. injection of the non-selective 5-HT receptor antagonist methysergide and another group received i.v. injection of the selective 5-HT1A receptor antagonist WAY-100635 20 min before exposure to intermittent hypercapnia. A control group received i.v. injection of saline. Peak phrenic nerve activity and respiratory rhythm parameters were analysed at baseline (T0), during each of five hypercapnic episodes, and 15, 30 and 60 min (T60) after the last hypercapnia. Intravenous injection of methysergide before exposure to acute intermittent hypercapnia induced development of amplitude pLTD at T60 (decreased by 46.1 ± 6.9%, P = 0.003). Conversely, in control and WAY-100635-pretreated animals, exposure to acute intermittent hypercapnia did not evoke amplitude pLTD. However, a long-term decrease in phrenic nerve frequency was evoked both in control (42 ± 4 breaths min(-1) at T0 versus 32 ± 5 breaths min(-1) at T60; P = 0.036) and in methysergide-pretreated animals (42 ± 2 breaths min(-1) at T0 versus 32 ± 3 breaths min(-1) at T60; P = 0.028). In WAY-100635 pretreated animals, frequency pLTD was prevented. These results suggest that 5-HT receptors modulate respiratory plasticity induced by acute intermittent hypercapnia in anaesthetized rats.

Intermittent hypercapnia produces long‐term changes of phrenic and renal sympathetic nerve activities that are serotonin dependent

This study was performed to investigate long‐term changes of peak phrenic (pPNA) and renal sympathetic nerve (RSNA) activities during and following acute intermittent hypercapnic exposures. Urethane anesthetized, vagotomized, paralyzed and mechanically ventilated male Sprague‐Dawley rats, were exposed to the acute intermittent hypercapnia protocol consisting of 5 hypercapnic episodes (15% CO2). Experimental groups were pretreated with either methysergide (3 mg/kg iv, MeHC) or WAY‐100635 (3 mg/kg iv, WAY) prior to the onset of the first hypercapnia. PPNA or RSNA and blood pressure were recorded throughout the protocol and analyzed before and during hypercapnic exposures, and 15 (T15), 30 (T30) and 60 (T60) minutes after the last hypercapnic episode. PPNA did not significantly change at T15, T30 and T60 compared to baseline. In the MeHC group, pPNA significantly decreased at T30 and T60 (by 41.3 ± 5.3%; and by 46.1 ± 6.9%, P&lt;0.005), compared to baseline values. In the WAY group, there were no significant changes in the pPNA at T15, T30, and T60 compared to baseline values. RSNA increased during hypercapnia and remained elevated at T15, T30 and T60 compared to baseline. In the WAY group RSNA increased during hypercapnia but returned to the baseline level at T60 (95.4 ± 23.1%). Acute intermittent hypercapnia induced long‐term depression of the pPNA following acute intermittent hypercapnia exposure only after blockade of serotonin receptors in anesthetized rats. On the other hand, acute intermittent hypercapnia evoked long‐term facilitation of the RSNA that was attenuated after blockade of serotonin receptors. Support: Croatian Science Foundation 09/165.

Changes in renal sympathetic nerve activity during and after exposure to acute intermittent hypercapnia

Elevated levels of carbon dioxide (hypercapnia) and/or decreased level of oxygen (hypoxia) act through neural networks to influence ventilatory and cardiovascular function. Both hypercapnic and hypoxic stimuli can evoke increase in sympathetic nerve activity and it appears that hypoxia can evoke prolonged duration of this increase. The present study was performed to investigate the renal sympathetic nerve activity in urethane‐anesthetized, mechanically ventilated Sprague‐Dawley rats exposed to five hypercapnic stimuli each lasting 3 minutes. Blood pressure and renal sympathetic nerve activity were measured and recorded throughout the experiment. Analysis was performed in the period before and during hypercapnic exposures (15% of the CO2 in the air), as well as 15, 30 and 60 minutes after the last hypercapnic episode. Renal sympathetic nerve activity increased to 190.3±22.8% during hypercapnia when compared to baseline. At 15 minutes after the last hypercapnic exposure nerve activity remained elevated at 138.0±14.8%. At 30 and 60 minutes renal sympathetic nerve activity was 136.8±21.5% and 131.8±18.3%, respectively. Acute intermittent hypercapnia evoked increase in renal sympathetic nerve activity that lasted at least 60 minutes after cessation of stimulus.This study was supported by Croatian Science Foundation.

The effects of repeated exposure to hypercapnia on arousal and cardiorespiratory responses during sleep in lambs

Arousal and cardio-respiratory responses to respiratory stimuli during sleep are important protective mechanisms that rapidly become depressed in the active sleep state when episodes of hypoxia or asphyxia are repeated: whether responses to repeated hypercapnia are similarly depressed is not known. This study aimed to determine if arousal and cardio-respiratory responses also become depressed with repeated episodes of hypercapnia during sleep and whether responses differ in active sleep and quiet sleep. Eight newborn lambs were instrumented to record sleep state and cardio-respiratory variables. Lambs were subjected to two successive 12 h sleep recordings, assigned as either sequential control and test days, or test and control days performed between 12.00 and 00.00 h. The control day was a baseline study in which the lambs breathed air to determine spontaneous arousal probability. During the test day, lambs were exposed to a 60 s episode of normoxic hypercapnia (Fractional inspired CO2 (F(ICO2)) = 0.08 and Fractional inspired O2(F(IO2)) = 0.21 in N2) during every quiet sleep and active sleep epoch. The probability of lambs arousing during the hypercapnic exposure exceeded the probability of spontaneous arousal during quiet sleep (58% versus 21%, chi2 = 54.0, P < 0.001) and active sleep (39% versus 20%, chi2 = 10.0, P < 0.01), though the response was less in active sleep. Exposure to hypercapnia also resulted in a significant increase in ventilation in quiet sleep (150 +/- 22%) and active sleep (97 +/- 23%, P < 0.05), though the increase was smaller in active sleep (P < 0.05). Small (< 5%) blood pressure increases and heart rate decreases were evident during hypercapnia in quiet sleep, but not in active sleep. Arousal and cardio-respiratory responses persisted with repetition of the hypercapnic exposure. In summary, although arousal and cardio-respiratory responses to hypercapnia are less in active sleep compared with quiet sleep, these protective responses are not diminished with repeated exposure to hypercapnia.

Diffuse optical measurement of cerebral metabolic rate of oxygen in adult brain

We combined diffuse optical (DOS) and correlation (DCS) spectroscopies to simultaneously measure the oxyhemoglobin (rHbO2), deoxyhemoglobin (rHb), total hemoglobin (rTHC) concentration and blood flow (rCBF) in adult human brain during a hypercapnic episode and sensorimotor stimulation. These measurements allowed calculation of the relative cerebral metabolic rate of oxygen (rCMRO2) in the human brain for the first time, to our knowledge, by use of all-optical methods. Briefly, 3 mW of light from three amplitude modulated lasers at 690, 785, and 830 nm were fiber-coupled to the head. Photons transmitted were detected in reflection mode. Spectroscopic analysis was carried to calculate rHb, rHbO2 and rTHC. A narrowband laser (5 mW at 800 nm), photon-counting, avalanche photo-diodes and a custom-build autocorrelator board was used for blood flow by fitting the obtained autocorrelation functions. The maximum penetration depth was about 2 cm from the top of the scalp and we report averaged values from the probed tissue volume after a partial volume correction1. As a first step towards validation in human brain, measurements were made in five subjects at a resting cerebral pCO2 and during 4-6 minute periods of increased pCO2 induced by respiration of a 6% CO2 gas mixture. The end tidal CO2, heart rate, blood pressure and arterial oxygenation were monitored continuously. A typical response is shown in Figure 1 (right panel). Over the five subjects a sustained mean CBF increase of 35.49.6% corresponding to 14.74.7 mmHg increase in pCO2 was observed. This corresponds to a 2.40.4 %/mmHg rise in CBF, well within the values reported in the literature (2-3.6%/mmHg). Seven male volunteers participated in the sensorimotor cortical activation studies. One subject further participated in a 3-T fMRI study in which BOLD and arterial spin-labeled (ASL) perfusion data were obtained sequentially to compare to optical results from the same subject. Figure 1 (left panel) shows group averaged results which indicate mean changes for rCBF rHBO2, rHB, rTHC, rCMRO2 of 3910%, 12.52.8 uM, -3.80.8 uM, 8.32.3 uM and 10.14.4% respectively in agreement with the literature. When the probe was placed away from the activation area, no significant, correlated changes were observed in the optical signals, demonstrating the local nature of the response. The feasibility of noninvasive optical measurement of blood flow and oxygen metabolism through the skull of the adult human is thus feasible, and the clinical potential of this hybrid, all-optical noninvasive, methodology is now being explored in patients suffering from severe head trauma. The optical technique offers a great deal of promise as a portable, non-invasive and relatively cheap modality, capable of doing longitudinal measurements of multiple important parameters.

Respiratory plasticity: differential actions of continuous and episodic hypoxia and hypercapnia

The objectives of this paper are: (1) to review advances in our understanding of the mechanisms of respiratory plasticity elicited by episodic versus continuous hypoxia in short to intermediate time domains (min to h); and (2) to present new data suggesting that different patterns of hypercapnia also elicit distinct forms of respiratory plasticity. Episodic, but not continuous hypoxia elicits long-term facilitation (LTF) of respiratory motor output. Phrenic LTF is a serotonin-dependent central neural mechanism that requires: (a) activation of spinal serotonin receptors; and (b) spinal protein synthesis. Continuous and episodic hypercapnia also elicit different mechanisms of plasticity. Continuous, severe hypercapnia (25 min of ∼10% inspired CO 2) elicits long-term depression (LTD) of phrenic motor output (−33±8% at 60 min post-hypercapnia) in anesthetized rats. In contrast, 3, 5 min hypercapnic episodes do not elicit LTD (9±17% at 60 min). We hypothesize that the response of respiratory motoneurons to serotonergic and noradrenergic modulation may contribute to pattern sensitivity to hypoxia and hypercapnia.

COPD Patients with Hypercapnic Respiratory Failure: Response to Therapy and Determinant of Intubation

Background The determinants of intubation and the response to therapy in COPD patients with hypercapnic respiratory failure were retrospectively reviewed. Methods This study involved a review of 132 episodes of hypercapnic respiratory failure(PaCO2≥50mmHg and pH≤7.35). The time frame for resolution or the time to intubation of patients who were admitted between 1996 and 1999 was analyzed. Results Out of 132 hypercapnic episodes, 49(37%) required intubation. A comparison was made with the 83 cases that responded to treatment. Patients requiring intubation had greater severity of illness, which included a higher APACHE II (Acute Physiology and Chronic Health Evaluation II) score (20±5 vs 14±4 ; p<0.01), a higher WBC, a higher serum BUM, and greater acidosis (pH, 7.23±0.11 vs 7.32±0.04 ; p<0.01). Those with the most severe acidosis(pH<7.20) had the highest intubation rate(87%) and shortest time to intubation (2±3 h). Conversely, those with an initial pH 7.31 to 7.35 were less likely to be intubated(20%), and had a longer time to intubation(97±121 h). The patients with a pH 7.21 to 7.25(4.1±2.9 day) required longer period of time to respond to medical treatment than patients with a pH of 7.31 to 7.35(2.2±3.1 day). Of those patients requiring intubation, half(55%) were intubated within 8 h of admission, and most (75%) within 24 h. Of those patients responding to treatment medical therapy, half(52%) recovered within 24 h and most (78%) recovered within 48 h. Conclusion Respiratory acidosis at the initial presentation is associated with an increased likelihood of intubation. This shold assist in deciding help with the decision whether to treat patients medically, institute noninvasive ventilation, or proceed to intubation.

Hypercapnic Respiratory Failure in COPD Patients: Response To Therapy

The clinical course of patients with acute exacerbations of underlying COPD presenting with hypercapnic respiratory failure was reviewed. This was a retrospective review of 138 episodes of hypercapnic respiratory failure (PaCO(2) > or = 50 mm Hg and pH < or = 7.35). Patients were admitted to the West Los Angeles VAMC Medical Intensive Care Unit between 1990 and 1994. Of the 138 hypercapnic episodes, 74 (54%) required intubation. Comparison was made with the 64 cases in which patients responded to medical therapy. Patients requiring intubation had a greater severity of illness, with a higher APACHE II (Acute Physiology and Chronic Health Evaluation II) score (18 +/- 5 vs 16 +/- 4; p < 0.01), higher WBC, higher serum BUN, and greater acidosis (pH, 7.26 +/- 0.07 vs 7.28 +/- 0.06; p = 0.08). Those with the most severe acidosis (pH < 7.20) had the highest intubation rate (70%) and shortest time to intubation (2 +/- 2 h), and they required the longest period of time to respond to medical therapy (69 +/- 60 h). With an initial pH of < 7.25, there was a consistently higher intubation rate. Conversely, those with an initial pH of 7.31 to 7. 35 were less likely to be intubated (45%), had a longer time to intubation (13 +/- 18 h), and had a more rapid response to medical therapy (30 +/- 18 h). Of those patients requiring intubation, most (78%) were intubated within 8 h of presentation, and the vast majority (93%) by 24 h. Of those patients responding to medical therapy, half (52%) recovered within 24 h and the vast majority (92%) recovered within 72 h. This study provides a better characterization of the response to therapy of COPD patients with hypercapnic respiratory failure. This should be useful in limiting or omitting medical therapy in high-risk patients, thereby avoiding delays in intubation as well as providing a framework for continued therapy in those more likely to improve.

Hypercapnia-induced long-term depression of respiratory activity requires alpha2-adrenergic receptors.

We investigated the effects of repeated hypercapnic episodes (inspired CO2 fraction = 0.10) on posthypercapnic respiratory nerve discharge. Anesthetized (urethan), vagotomized, and artificially ventilated rats were presented with three consecutive 5-min episodes of hyperoxic hypercapnia, separated by 5 min of hyperoxic normocapnia (inspired O2 fraction = 0.5). Respiratory nerve discharge and blood gases were recorded before and 30 and 60 min after the final hypercapnic episode. Posthypercapnia, arterial PCO2 was maintained within 1 Torr of initial baseline values. Integrated phrenic and hypoglossal burst amplitudes decreased posthypercapnia by up to 46 +/- 17 and 55 +/- 13% of baseline values, respectively, and remained reduced for at least 1 h [long-term depression (LTD)]. The protocol was repeated in rats pretreated with the alpha2-adrenergic antagonists yohimbine HCl (0.5 mg/kg; n = 7) or 2-[2-(2-methoxy-1,4-benzodioanyl)]imidazoline (RX-821002) HCl (0.25 mg/kg; n = 3). Both drugs attenuated LTD in the phrenic and hypoglossal neurograms. Results indicate that episodic hypercapnia elicits a yohimbine- and RX-821002-sensitive LTD of respiratory nerve activity in rats, suggesting that LTD requires alpha2-receptor activation.

Echocardiographic evidence of aortopulmonary collaterals in premature infants after closure of ductus arteriosus.

Aortopulmonary collaterals occur in a variety of congenital heart diseases, in chronic pulmonary infection and abscesses, in association with lung tumors, and after multiple pulmonary emboli. In patients with congenital cyanotic heart disease aortopulmonary collaterals mainly occur in conditions with reduced pulmonary blood flow. We investigated 12 preterm low-birth-weight infants, gestational age 29.3+/-3.3 weeks, with respiratory failure who suffered from moderate to severe chronic lung disease after a period of mechanical ventilation. All patients developed aortopulmonary collaterals after closure of a patent ductus arteriosus. Aortopulmonary collaterals could be displayed clearly by color Doppler echocardiography and originated mainly from the descending aorta or the aortic arch. Hypoxic and hypercapnic episodes favored the development of aortopulmonary collaterals, which disappeared after pulmonary hemodynamics and respiratory function had improved. In only one patient coiling of a large col lateral vessel had to be performed. Systemic-to-pulmonary collateral vessels potentially aggravate chronic lung disease by increasing collateral pulmonary blood flow and reducing lung compliance. We conclude that aortopulmonary collaterals occur in bronchopulmonary dysplasia and can cause major problems in ventilated premature infants. Echocardiographic evaluation is important to prevent aggravation of chronic lung disease of infants at risk.

Tracheobronchography and balloon dilatation in acquired neonatal tracheal stenosis.

Between 1988 and 1992, 18 mechanically ventilated newborn babies (mean weight 1300 g and gestational age 30 weeks) presented with deteriorating respiratory failure at a mean age of 29 days. All developed increased oxygen requirements, hypoxic and hypercapnic episodes, and radiological changes of fixed lobar emphysema or recurrent atelectasis which sometimes changed sides from one day to another. Tracheobronchography with iopydol-iopydone was normal in five (27%) cases, but in 13 showed tracheobronchial stenosis localised to the lower trachea (seven cases), to the right main bronchus (three cases), or including the left main bronchus (four cases). Eleven of these 13 patients underwent endoscopy and balloon dilatation of the stenotic area. Five patients died, one before endoscopy, one immediately after endoscopies, and three subsequently with severe bronchopulmonary dysplasia. The other six babies recovered without any sequelae after balloon dilatation.

Nifedipine reduces the increases in cerebral blood flow during hypercapnic episodes

1. 1. Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation which allowed for continuous monitoring of flow over the several hours of the study. 2. 2. Brief challenges with carbon dioxide (CO 2) increased the CBF. 3. 3. Nifedipine (1.00 mg/kg), a dihydropyridine calcium antagonist, attenuated the response of the animal to hypercapnia, while leaving the basal flow rate unchanged. 4. 4. This study may have significant implications as to the effect of nifedipine on CBF. 5. 5. Since similar results have been obtained with nifedipine in anoxia, this study suggests that the responses to anoxia and hypercapnia are interrelated and that the resulting hyperemia may be governed by the same mechanisms.