Mechanical Hyperventilation Research Articles

Radiation Induced Lung Injury in Rats after Pre-Oxygenation Radiotherapy

Deep inspiratory breath holding (DIBH) has been widely used during the radiotherapy of thoracic tumors. The main disadvantage of voluntary DIBH is the short duration of each breath hold. The hypocapnia induced by hyperoxia (oxygen concentration > 50%) pre-oxygenation (PreO2) combined with mechanical hyperventilation has been reported to prolong the duration of single breath hold, but its safety remains controversial, especially the sensitivity of lung tissue to radiation damage under hyperoxia exposure has not been elucidated. In this study, we aim to investigate the changes of radiation induced lung injury in rats after PreO2 radiation. We evaluated the lung tissue of rats at different time points (48h, 2w, 4w, 8w, 12w) after thoracic radiation (15Gy single fraction to the right lung), and sequenced the transcriptome of lung tissue at 48 hours after irradiation. Rat cohorts (n = 7/group): 1. Control (Con); 2. Radiation group (RT); 3. Pre-oxygenation (oxygen concentration > 90%) for 8 hours before thoracic radiation (PreO2). The inflammatory exudation emerged in the pulmonary interstitium at 48 hours, and reached the most serious alveolitis after four weeks of irradiation (the comparison of alveolitis scores in RT4w vs Con4w and PreO2(4w) vs Con4w, P<0.001) on hematoxylin-eosin staining. While the alveolitis scores in RT group and PreO2 group were not statistically different at each time point. Masson staining showed that the pulmonary fibrosis in the RT group and the PreO2 group reached an obvious pathological change at 12 weeks after irradiation, but the difference between the two groups was not significant. Transcriptome sequencing showed that the number of differential genes in PreO2 vs Con was 559 (302 up-regulated genes and 257 down-regulated genes). The GO enrichment analysis indicated that chromosome segregation was the most significant functional item with P value in the comparative analysis, and the KEGG enrichment analysis suggested that cell division was the most significant enrichment pathway of these differential genes. While there was a small quantity of differential genes in PreO2 vs RT group (3 up-regulated genes and 12 down-regulated genes). Pentose and glucuronate conversions were the most significant enrichment pathway of these differential genes. This study demonstrated that PreO2 radiotherapy did not increase the severity of radiation induced lung injury in rats compared to conventional radiotherapy. Further study should be conducted to confirm these results and to investigate the regulatory mechanism of pneumonia caused by PreO2 radiotherapy.

Preoxygenation with a 50% Concentration of Oxygen for 15 Minutes might Safely and Feasibly Prolong the Breath-Hold Duration during Radiotherapy: A Pilot Study

<h3>Purpose/Objective(s)</h3> Voluntary deep inspiration breath-hold (DIBH) has been wildly used during radiation for thoracic and abdominal tumors. While the main disadvantage of voluntary DIBH is its short duration per single breath-hold. Preoxygenation with a high concentration of oxygen (more than 50%) combined with mechanical hyperventilation induced hypocapnia has been used for prolonging the single breath-hold duration, however, its safety is still a concern. In this study, we aimed to investigate whether simple preoxygenation with a relatively safe oxygen concentration of 50% can feasibly prolong the single breath-hold duration. <h3>Materials/Methods</h3> 12 healthy volunteers aged 21-48 years (6 males and 6 females) without previous cardiovascular diseases were included. The single DIBH duration of room air in resting-state, the single DIBH duration of room air after 5 min, 15 min, and 30 min preoxygenation with 50% concentration of oxygen, respectively, were evaluated and compared using paired t-test. <h3>Results</h3> The mean DIBH duration in room air in resting-state was 51.5 ± 12.97 seconds. Compared with DIBH in room air, after 5, 15, and 30 minutes preoxygenation with 50% concentration of oxygen, the DIBH duration in room air was significantly increased up to 91.9 ± 28.3 (p<0.0001), 115.5 ±25.5 (p<0.0001), and 122.1 ±28.4 seconds (p<0.0001), respectively. Furthermore, compared with 5 minutes of preoxygenation, the DIBH duration after 15 and 30 minutes of preoxygenation was significantly increased with 23.5 ± 9.7 (p<0.0001) and 30.2 ± 13.7 seconds (p<0.0001). Compared with 15 minutes of preoxygenation, the DIBH duration after 30 minutes of preoxygenation was only increased with 6.7 ± 5.4 seconds (p=0.0013). <h3>Conclusion</h3> This pilot study demonstrated that simple preoxygenation with a 50% concentration of oxygen for 15 minutes might safely and feasibly prolong the DIBH duration during radiotherapy. Further studies are warranted to confirm these results and to identify how many cycles of a single breath-hold can be prolonged. This study has been supported by the National Nature Science Foundation of China (82171890 & 81701683), Key Research and Development Projects of Zhejiang Provincial Science and Technology Department (2021C03122), Health Commission of Zhejiang Province (2020KY131), and Zhejiang Provincial Key Discipline of Traditional Chinese Medicine (2017-XK-A32).

The influence of CO2 on spatiotemporal features of mechanically induced cough in anesthetized cats

Effective cough requires a significant increase in lung volume used to produce the shear forces on the airway to clear aspirated material. This increase in tidal volume during cough, along with an increase in tidal frequency during bouts of paroxysmal cough produces profound hyperventilation and thus reduces arterial CO2. While there are several reports in the literature regarding the effects of hypercapnia, hyperoxia, and hypoxia on cough, there is little research quantifying the effects of hypocapnia on the cough reflex. We hypothesized that decreased CO2 would enhance coughing. In 12 spontaneously breathing adult male cats, we compared bouts of prolonged mechanically stimulated cough, in which cough induced hyperventilation (CHV) was allowed to occur, with isocapnic cough trials where we maintained eupneic end-tidal CO2 by adding CO2 to the inspired gas. Isocapnia slightly increased cough number and decreased esophageal pressures with no change in EMG magnitudes or phase durations. The cough-to-eupnea transition was also analyzed between CHV, isocapnia, and a third group of animals that were mechanically hyperventilated to apnea. The transition to eupnea was highly sensitive to added CO2, and CHV apneas were much shorter than those produced by mechanical hyperventilation. We suggest that the cough pattern generator is relatively insensitive to CHV. In the immediate post-cough period, the appearance of breathing while CO2 is very low suggests a transient reduction in apneic threshold following a paroxysmal cough bout.

Severe portal and systemic acidosis during CO2-laparoscopy compared to helium or gasless laparoscopy and laparotomy in a rodent model: an experimental study

Background and aimsThis experimental study assesses the influence of different gases and insufflation pressures on the portal, central-venous and peripheral-arterial pH during experimental laparoscopy.MethodsFirstly, 36 male WAG/Rij rats were randomized into six groups (n = 6) spontaneously breathing during anaesthesia: laparoscopy using carbon dioxide or helium at 6 and 12 mmHg, gasless laparoscopy and laparotomy. 45 and 90 min after setup, blood was sampled from the portal vein, vena cava and the common femoral artery with immediate blood gas analysis. Secondly, 12 animals were mechanically ventilated at physiological arterial pH during 90 min of laparotomy (n = 6) or carbon dioxide laparoscopy at 12 mmHg (n = 6) with respective blood gas analyses.ResultsOver time, in spontaneously breathing rats, carbon dioxide laparoscopy caused significant insufflation pressure-dependent portal acidosis (pH at 6 mmHg, 6.99 [6.95–7.04] at 45 min and 6.95 [6.94–6.96] at 90 min, pH at 12 mmHg, 6.89 [6.82–6.90] at 45 min and 6.84 [6.81–6.87] at 90 min; p < 0.05) compared to laparotomy (portal pH 7.29 [7.23–7.30] at 45 min and 7.29 [7.20–7.30] at 90 min; p > 0.05). Central-venous and peripheral-arterial acidosis was significant but less severely reduced during carbon dioxide laparoscopy. Laparotomy, helium laparoscopy and gasless laparoscopy showed no comparable acidosis in all vessels. Portal and central-venous acidosis during carbon dioxide laparoscopy at 12 mmHg was not reversible by mechanical hyperventilation maintaining a physiological arterial pH (pH portal 6.85 [6.84–6.90] (p = 0.004), central-venous 6.93 [6.90–6.99] (p = 0.004), peripheral-arterial 7.29 [7.29–7.31] (p = 0.220) at 90 min; Wilcoxon–Mann–Whitney test).ConclusionCarbon dioxide laparoscopy led to insufflation pressure-dependent severe portal and less severe central-venous acidosis not reversible by mechanical hyperventilation.

Hypercapnia versus normocapnia for emergence from desflurane anaesthesia

Rapid emergence from general anaesthesia is desirable only if safety is not sacrificed. Mechanical hyperventilation during hypercapnia produced by carbon dioxide infusion into the inspired gas mixture or by rebreathing was reported to shorten emergence time from inhalation anaesthesia. To test the hypothesis that hypercapnia produced by hypoventilation before desflurane cessation shortens emergence time from general anaesthesia (primary hypothesis) and reduces undesirable cardiorespiratory events. A single-blinded randomised controlled study. A single university hospital. Fifty adult patients undergoing elective abdominal surgery under general anaesthesia using desflurane inhalation and intra-operative epidural anaesthesia. The patients were randomly assigned to either the normocapnia or hypercapnia group. Emergence time from desflurane anaesthesia and comparison of the incidence of 11 predefined undesirable cardiorespiratory events during and after emergence from anaesthesia between the groups. Forty-six patients were included in the analysis. End-tidal carbon dioxide concentrations at cessation of desflurane were 35 ± 6 mmHg (mean ± SD) and 52 ± 6 mmHg in normocapnia (n = 23) and hypercapnia groups (n = 23), respectively. Emergence time was significantly faster in the hypercapnia group than the normocapnia group: 9.4 ± 2.4 min, hypercapnia: 5.5 ± 2.6 min, (P < 0.001) with a difference of 3.8 min on average (95% CI: 2.4 to 5.3). Spontaneous breathing established before recovery of consciousness was more evident in hypercapnia patients (normocapnia: 13%, hypercapnia: 96%, P < 0.001). Hypercapnia patients had more episodes of bradypnoea and apnoea before emergence of consciousness. In contrast, after tracheal extubation, incidences of bradypnoea and hypopnoea were more common in the normocapnia group. Undesirable cardiovascular events were not common, and no group differences were observed during emergence and postextubation periods. Hypoventilation-induced hypercapnia before desflurane cessation shortens the emergence time without causing additional clinically significant undesirable events. UMIN Clinical Trials Registry (UMIN000020143) https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000023266&language=E.

Hypocapnia Alone Fails to Provoke Important Electrocardiogram Changes in Coronary Artery Diseased Patients.

BackgroundThere is still an urgent clinical need to develop non-invasive diagnostic tests for early ischemic heart disease because, once angina occurs, it is too late. Hypocapnia has long been known to cause coronary artery vasoconstriction. Some new cardiology tests are accompanied by the claim that they must have potential diagnostic value if hypocapnia enhances their cardiac effects in healthy subjects. But no previous study has tested whether hypocapnia produces bigger cardiac effects in patients with angina than in healthy subjects.MethodsSevere hypocapnia (a PetCO2 level of 20 mmHg) lasting >15 min was mechanically induced by facemask, while conscious and unmedicated, in 18 healthy subjects and in 10 patients with angina and angiographically confirmed coronary artery disease, awaiting by-pass surgery. Each participant was their own control in normocapnia (where CO2 was added to the inspirate) and the order of normocapnia and hypocapnia was randomized. Twelve lead electrocardiograms (ECG) were recorded and automated measurements were made on all ECG waveforms averaged over >120 beats. 2D echocardiography was also performed on healthy subjects.ResultsIn the 18 healthy subjects, we confirm that severe hypocapnia (a mean PetCO2 of 20 ± 0 mmHg, P < 0.0001) consistently increased the mean T wave amplitude in leads V1–V3, but by only 31% (P < 0.01), 15% (P < 0.001) and 11% (P < 0.05), respectively. Hypocapnia produced no other significant effects (p > 0.05) on their electro- or echocardiogram. All 10 angina patients tolerated the mechanical hyperventilation well, with minimal discomfort. Hypocpania caused a similar increase in V1 (by 39%, P < 0.05 vs. baseline, but P > 0.05 vs. healthy controls) and did not induce angina. Its effects were no greater in patients who did not take β-blockers, or did not take organic nitrates, or had the worst Canadian Cardiovascular Society scores.ConclusionNon-invasive mechanical hyperventilation while awake and unmedicated is safe and acceptable, even to patients with angina. Using it to produce severe and prolonged hypocapnia alone does produce significant ECG changes in angina patients. But its potential diagnostic value for identifying patients with coronary stenosis requires further evaluation.

Feasibility of endoscope guided orotracheal intubation without muscle relaxant

Objective To evaluate the feasibility of endoscope-guided orotracheal intubation without muscle relaxant after induction of anesthesia with remifentanil and propofol. Methods Forty patients with ASA class Ⅰ or Ⅱ scheduled for elective operation under general anesthesia were randomly divided into 2 groups (n=20): subjective to endotracheal intubation without muscle relaxant(group N) or endotracheal intubation with rocuronium, a muscle relaxant (group R). Anesthesia in both groups was induced with midazolam, remifentanil, and propofol, and maintained with propofol(3 mg·kg-1·h-1) and remifentanil(0.3 μg·kg-1·min-1) after induction. When patients became unconscious with BIS<60, endotracheal intubation was performed after 2 min mechanical hyperventilation. The number of cases of successful intubation, number of attempts, duration of each attempt, total intubation time, and incidence of adverse reactions during the procedure were recorded. Results There was no difference between the two groups in the number of cases of successful intubation, number of attempts, total intubation time, adverse reactions during the procedure and the incidence of postoperative complications(P>0.05). The comprehensive satisfaction rate for the endotracheal intubation was not different in the two groups with 85% in group N and 95% in group R(P>0.05). Conclusions Endoscope-guided orotracheal intubation is safe and effective in patients without a muscle relaxant. Key words: Muscle relaxant; Endotracheal intubation; Endoscope

Isocapnic hyperventilation provides early extubation after head and neck surgery: A prospective randomized trial.

Isocapnic hyperventilation (IHV) shortens recovery time after inhalation anaesthesia by increasing ventilation while maintaining a normal airway carbon dioxide (CO2)-level. One way of performing IHV is to infuse CO2 to the inspiratory limb of a breathing circuit during mechanical hyperventilation (HV). In a prospective randomized study, we compared this IHV technique to a standard emergence procedure (control). Thirty-one adult ASA I-III patients undergoing long-duration (>3hours) sevoflurane anaesthesia for major head and neck surgery were included and randomized to IHV-treatment (n=16) or control (n=15). IHV was performed at minute ventilation 13.6±4.3L/min and CO2 delivery, dosed according to a nomogram tested in a pilot study. Time to extubation and eye-opening was recorded. Inspired (FICO2) and expired (FETCO2) CO2 and arterial CO2 levels (PaCO2) were monitored. Cognition was tested preoperatively and at 20, 40 and 60minutes after surgery. Time from turning off the vapourizer to extubation was 13.7±2.5minutes in the IHV group and 27.4±6.5minutes in controls (P<.001). Two minutes after extubation, PaCO2 was 6.2±0.5 and 6.2±0.6 kPa in the IHV and control group respectively. In 69% (IHV) vs 53% (controls), post-operative cognition returned to pre-operative values within 40 minutes after surgery (NS). Incidences of pain and nausea/vomiting did not differ between groups. In this randomized trial comparing an IHV method with a standard weaning procedure, time to extubation was reduced with 50% in the IHV group. The described IHV method can be used to decrease emergence time from inhalation anaesthesia.

Evaluation of a method for isocapnic hyperventilation: a clinical pilot trial.

Isocapnic hyperventilation (IHV) is a method that shortens time to extubation after inhalation anaesthesia using hyperventilation (HV) without lowering airway CO2 . In a clinical trial on patients undergoing long-duration sevoflurane anaesthesia for major ear-nose-throat (ENT) surgery, we evaluated the utility of a technique for CO2 delivery (DCO2 ) to the inspiratory limb of a closed breathing circuit, during HV, to achieve isocapnia. Fifteen adult ASA 1-3 patients were included. After end of surgery, mechanical HV was started by doubling baseline minute ventilation. Simultaneously, CO2 was delivered and dosed using a nomogram developed in a previous experimental study. Time to extubation and eye opening was recorded. Inspired (FICO2 ) and expired (FETCO2 ) CO2 and arterial CO2 levels were monitored during IHV. Cognition was tested pre-operatively and at 20, 40 and 60 min after surgery. A DCO2 of 285 ± 45 ml/min provided stable isocapnia during HV (13.5 ± 4.1 l/min). The corresponding FICO2 level was 3.0 ± 0.3%. Time from turning off the vaporizer (1.3 ± 0.1 MACage) to extubation (0.2 ± 0.1 MACage) was 11.3 ± 1.8 min after 342 ± 131 min of anaesthesia. PaCO2 and FETCO2 remained at normal levels during and after IHV. In 85% of the patients, post-operative cognition returned to pre-operative values within 60 min. In this cohort of patients, a DCO2 nomogram for IHV was validated. The patients were safely extubated shortly after discontinuing long-term sevoflurane anaesthesia. Perioperatively, there were no adverse effects on arterial blood gases or post-operative cognition. This technique for IHV can potentially be used to decrease emergence time from inhalation anaesthesia.

Effects of short-term mechanical hyperventilation on cerebral blood flow and dynamic cerebral autoregulation in critically ill patients with sepsis

In sepsis, higher PaCO2 levels are associated with impaired dynamic cerebral autoregulation (dCA), which may expose the brain to hypo- and hyperperfusion during acute fluctuations in blood pressure. We hypothesised that short-term mechanical hyperventilation would dCA in critically ill patients with sepsis. Seven mechanically ventilated septic patients were included. We assessed dCA before and after 30 min of mechanical hyperventilation. Transfer function analysis of spontaneous oscillations in transcranial Doppler-based middle cerebral artery blood flow velocity (MCAv) and invasive mean arterial blood pressure was used to assess dCA. Mechanical enhance hyperventilation reduced the median PaCO2 from 5.3 (IQR, 5.0–6.5) to 4.7 (IQR, 4.2–5.1) kPa (p < 0.05). This was associated with a reduction in the median MCAv from 57 (IQR, 33–68) to 32 (IQR, 21–40) cm sec−1 (p < 0.05). Apart from a small increase in gain in the low frequency range (2.32 [IQR 1.80–2.41] vs. 2.59 (2.40–4.64) cm mmHg−1 sec−1; p < 0.05), this was not associated with any enhancement in dCA. In conclusion, cerebral CO2 vasoreactivity was found to be preserved in septic patients; nevertheless, and in contrast to our working hypothesis, short-term mechanical hyperventilation did not enhance dCA.

A call for standards on perioperative CO2 regulation

To The Editor, The Journal recently published the International Standards to the Practice of Anesthesia. These Standards mandate the use of capnography, but they fail to provide guidelines for carbon dioxide management. Except under rare circumstances, carbon dioxide is inert, odourless, tasteless, invisible, and remarkably benign and beneficial. It is heavier than other atmospheric gases, so it accumulates in dependent locations, such as mines, where air circulation is lacking. Under these conditions, it displaces oxygen and causes death by drowning. Since this phenomenon was attributed to toxicity in earlier times and early gas research confused CO2 effects with carbon monoxide toxicity, carbon dioxide remains widely but mistakenly feared as toxic and narcotic. All vertebrate cells produce CO2 continuously. It saturates body tissues and fluids, and it equilibrates with the external environment. Carotid and aortic respiratory chemoreceptors gradually adapt to and maintain this equilibrium. Synergistic combinations of hypercarbia and hypoxemia exponentially increase chemoreceptor activity and respiratory drive. Hyperventilation is unnatural and abnormal in all circumstances. It confers no tangible benefits, and it may cause serious adverse events, including ‘‘shallow water blackout syndrome’’, brain damage in mountain climbers, and increased morbidity and mortality in otherwise healthy polio victims. Nowadays, its traditional use to counteract brain swelling is discouraged. Mechanical hyperventilation rapidly depletes CO2 tissue reserves, which obtunds chemoreceptors and undermines respiratory drive. Mechanical hyperventilation during anesthesia originated before pulse oximetry and capnography were available. In that bygone era, carbon dioxide was assumed to be a ‘‘toxic waste gas’’ that must be rid from the body rather than an essential element of normal physiology that is rapidly depleted by mechanical hyperventilation and requires careful conservation. It was not understood that hyperventilation damages lung tissues, impairs tissue perfusion and oxygenation, inhibits opioid clearance, traps opioids in brain tissues, and depletes CO2 reserves necessary for normal respiratory chemoreceptor activity. Moreover, it was not understood that mild hypoventilation reduces blood viscosity beneficially, increases cardiac output, promotes tissue perfusion and oxygenation, protects lung tissues, preserves tissue reserves of carbon dioxide, offsets the respiratory depressant effects of opioids, and prevents opioid ‘‘trapping’’ in brain tissues. During that past era, evidence was often misinterpreted or overlooked in favour of pre-existing beliefs about carbon dioxide toxicity. For example, Boniface and Brown mistakenly concluded that CO2 causes toxic depression of cardiac contractility, even though their study documented beneficial decreases in systemic vascular resistance that offered a simpler explanation for decreased cardiac work. Unfortunately, anesthesia hyperventilation remains entrenched, even though critical care experts have embraced the safety of permissive hypercapnia. The practice is reinforced by the routine observation that hyperventilated patients usually breathe adequately upon anesthetic emergence, provided that opioid dosage has been carefully constrained. This is because conscious awareness sustains breathing despite the absence of chemoreceptor activity, particularly in the presence of pain. L. S. Coleman, MD (&) Fresno Dental Surgery Center, 888 E. Divisadero St. #209, Fresno, CA 93721, USA e-mail: lewis_coleman@yahoo.com

Is it inflation or central inspiration that attenuates baroreflex sensitivity (BRS) in Man?.

Breathing reduces the heart period component of BRS. Is the cause predominantly pulmonary inflation or central inspiration? Hypocapnia (HA) augments the pulmonary stretch reflex but reduces the central respiratory rhythm. If HA further reduces BRS, the predominant cause of this respiratory attenuation is inflation, whereas if HA increases BRS the predominant cause is central inspiration.BRS was measured by spontaneous sequence analysis in 7 healthy subjects in eupnea (PetCO2 38 ± 1 mmHg) and during mechanical hyperventilation by facemask, where subjects breathed with the ventilator, in either normocapnia or HA.In eupnea BRS was attenuated in inflation/inspiration vs. deflation/expiration (11 ±3 ms/mmHg vs. 24 ±7 ms/mmHg, P&lt;0.005). Averaged mean blood pressure was 90 ±3 mmHg and mean heart period was 0.88 ± 0.06 s. Mechanical hyperventilation (PetCO2 = 39 ±1 mmHg) had no signficant effects vs. eupnea on blood pressure, heart period or BRS.HA (PetCO2 = 23±0 mmHg) had no significant effect on blood pressure or heart period but reduced mean BRS in inflation/inspiration to 6±1 ms/mmHg (n=6, P&lt; 0.001). This effect also carried over to reduce BRS (7 ± 2 ms/mmHg, n=7, P&lt;0.05) in deflation/expiration.Because HA further reduces (rather than increases) BRS, we conclude that under these conditions the cause of the respiratory attenuation of BRS is predominantly inflation rather than central inspiration.

Effects of hypercapnia and hypocapnia on ventilatory variability and the chaotic dynamics of ventilatory flow in humans

In humans, lung ventilation exhibits breath-to-breath variability and dynamics that are nonlinear, complex, sensitive to initial conditions, unpredictable in the long-term, and chaotic. Hypercapnia, as produced by the inhalation of a CO(2)-enriched gas mixture, stimulates ventilation. Hypocapnia, as produced by mechanical hyperventilation, depresses ventilation in animals and in humans during sleep, but it does not induce apnea in awake humans. This emphasizes the suprapontine influences on ventilatory control. How cortical and subcortical commands interfere thus depend on the prevailing CO(2) levels. However, CO(2) also influences the variability and complexity of ventilation. This study was designed to describe how this occurs and to test the hypothesis that CO(2) chemoreceptors are important determinants of ventilatory dynamics. Spontaneous ventilatory flow was recorded in eight healthy subjects. Breath-by-breath variability was studied through the coefficient of variation of several ventilatory variables. Chaos was assessed with the noise titration method (noise limit) and characterized with numerical indexes [largest Lyapunov exponent (LLE), sensitivity to initial conditions; Kolmogorov-Sinai entropy (KSE), unpredictability; and correlation dimension (CD), irregularity]. In all subjects, under all conditions, a positive noise limit confirmed chaos. Hypercapnia reduced breathing variability, increased LLE (P = 0.0338 vs. normocapnia; P = 0.0018 vs. hypocapnia), increased KSE, and slightly reduced CD. Hypocapnia increased variability, decreased LLE and KSE, and reduced CD. These results suggest that chemoreceptors exert a strong influence on ventilatory variability and complexity. However, complexity persists in the quasi-absence of automatic drive. Ventilatory variability and complexity could be determined by the interaction between the respiratory central pattern generator and suprapontine structures.

Excitation of Medullary Respiratory Neurons in REM Sleep

To study tonic inputs to medullary respiratory neurons during rapid eye movement (REM) sleep. Single medullary-respiratory-neuron recordings during sleep with spontaneous breathing and during apnea caused by mechanical hyperventilation. Academic laboratory. Three tracheostomized adult cats implanted for polysomnography and extracellular microelectrode recordings. Single medullary-respiratory-neuron recordings during spontaneous breathing and mechanical hyperventilation to apnea during non-REM (NREM) and REM sleep. Most but not all respiratory cells of all types (pre-inspiratory, decrementing, augmenting and late inspiratory, phase-spanning, and expiratory) were more active in REM sleep than in NREM sleep during both spontaneous breathing and apnea induced by mechanical hyperventilation. The mean discharge rate of the cells during spontaneous breathing in NREM sleep was 16.7 impulses per second and in REM sleep was 26.5 impulses per second. During ventilator-induced apnea, the mean rates were 10 impulses per second in NREM sleep and 17.5 per second during REM sleep. The increase in activity in REM sleep occurred after a delay of several seconds from the onset of REM sleep. Respiratory cells were excited at times individually and at other times simultaneously in either a reciprocal or nonreciprocal pattern. The degree of excitation of a neuron in REM sleep during ventilator-induced apnea was proportional to the degree of excitation of the neuron in REM sleep during spontaneous breathing. Medullary respiratory neurons are excited individually and collectively in REM sleep. The excitation occurs with a delay after the onset of the state and can stimulate and/or disorganize breathing.

Hypocapnia reduces the T wave of the electrocardiogram in normal human subjects

During voluntary hyperventilation in unanesthetized humans, hypocapnia causes coronary vasoconstriction and decreased oxygen (O(2)) supply and availability to the heart. This can induce local epicardial coronary artery spasm in susceptible patients. Its diagnostic potential for detection of early heart disease is unclear. This is because such hypocapnia produces an inconsistent and irreproducible effect on electrocardiogram (ECG) in healthy subjects. To resolve this inconsistency, we have applied two new experimental techniques in normal, healthy subjects to measure the effects of hypocapnia on their ECG: mechanical hyperventilation and averaging of multiple ECG cycles. In 15 normal subjects, we show that hypocapnia (20 +/- 1 mmHg) significantly reduced mean T wave amplitude by 0.1 +/- 0.0 mV. Hypocapnia also increased mean heart rate by 4 beats/min without significantly altering blood pressure, ionized calcium or potassium levels, or the R wave or other features of the ECG. We therefore provide the first unequivocal demonstration that hypocapnia does consistently reduce T wave amplitude in normal, healthy subjects.

Total Intravenous Anesthesia for Repair of Congenital Diaphragmatic Hernia: A Case Report

Congenital diaphragmatic hernia is a cardiopulmonary anomaly that causes severe respiratory disorder. Traditionally, inhalational anesthetics with mechanical hyperventilation, opioids, and muscle relaxants are used in anesthesia for repair surgery. In this case, we used total intravenous anesthesia combined with high-frequency oscillatory ventilation and inhaled nitric oxide for surgical repair of the diaphragm. After surgery, the patient recovered well and was discharged from hospital 1 month later.

Two Reports of Propofol Anesthesia Associated with Metabolic Acidosis in Adults

Two Reports of Propofol Anesthesia Associated with Metabolic Acidosis in Adults

Acute hyperventilation leading to hypocalcaemia during spinal anaesthesia

SummaryThe most common cause of hypocalcaemia under general anaesthesia is acute mechanical hyperventilation, but hypocalcaemia during spinal anaesthesia has not been reported. This case report describes the development of hypocalcaemia due to hyperventilation in a patient undergoing appendicectomy under spinal anaesthesia. The diagnostic features of hypocalcaemia and its treatment are explained in detail.

Hypocapnia decreases the amount of rapid eye movement sleep in cats.

Sleep is disturbed at high altitudes. Low PO2 levels at high altitude cause hyperventilation, which results in secondary hypocapnia (low PaCO2 levels). Thus, although sleep disruption at high altitudes is generally assumed to be caused by hypoxia, it may instead be the result of hypocapnia. To determine whether hypocapnia disrupts sleep. Four cats were studied for a total of 345 hours of sleep recordings. Two methods were used to test this idea. First we studied their sleep when the cats breathed oxygen concentrations (15% and 10%) equivalent to those at approximately 12,000 feet and 21,000 feet. Then we studied their sleep again in response to the same hypoxic stimuli but with CO2 added to the inspirate to maintain normal CO2 levels. Second, we used mechanical hyperventilation to vary the levels of CO2 while maintaining normal O2 levels. Hypoxia (10% O2) decreased the amount of rapid eye movement sleep to about 20% of normal, and adding back CO2 restored rapid eye movement sleep to approximately 70% of normal. Periodic breathing and apneas were not observed during hypoxia in sleep. When mechanical hyperventilation lowered the CO2 to 85%, 75%, and 65% of normal, rapid eye movement sleep decreased progressively from a control level of 17% of total recording time to 12%, 7%, and 4%, respectively. We conclude that hypocapnia rather than hypoxia may account for most of the sleep disturbance at high altitudes.

Cerebral glucose and oxygen metabolism in patients with fulminant hepatic failure

Hyperammonemia and hyperventilation are consistent findings in patients with fulminant hepatic failure (FHF), which may interfere with cerebral glucose and oxygen metabolism. The aim of the present study is to evaluate whether cerebral oxidative metabolism is preserved early in the course of FHF and whether hyperventilation has an influence on this. We included 16 patients with FHF, 5 patients with cirrhosis of the liver, and 8 healthy subjects. Concomitant blood sampling from an arterial catheter and a catheter in the jugular bulb and measurement of cerebral blood flow by the xenon 133 wash-out technique allowed calculation of cerebral uptake of glucose (CMRgluc) and oxygen (CMRO2). Both CMRgluc and CMRO2 were reduced in patients with FHF compared with those with cirrhosis and healthy subjects, i.e., 11.8 +/- 2.7 v 18.3 +/- 5.5 and 28.5 +/- 6.6 micromol/100 g/min (P <.05) and 86 +/- 18 v 164 +/- 42 and 174 +/- 27 micromol/100 g/min (P <.05). Arteriovenous difference in oxygen and oxygen-glucose index were normal in patients with FHF. Institution of mechanical hyperventilation did not affect glucose and oxygen uptake and hyperventilation did not affect lactate-pyruvate ratio or lactate-oxygen index. In conclusion, we found that cerebral glucose and oxygen consumption are proportionally decreased in patients with FHF investigated before clinical signs of cerebral edema. Our data suggest that cerebral oxidative metabolism is retained at this stage of the disease without being compromised by hyperventilation.