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Purpose: Ecchymosis and edema are the most common complications in patients following rhinoplasty in the early postoperative period. Vasoconstriction created by hypocarbia may have a positive effect on postoperative ecchymosis. The aim of this study was to evaluate the effect of mild hypocapnia induced in rhinoplasty on the severity of periorbital ecchymosis., Methods: The study was carried out retrospectively in the digital photographs (control group and study group) of 31 participants who underwent open technical rhinoplasty between January and March 2019. During the operation, partial carbon dioxide pressure in the study group was kept in the range of 32 to 38 mmHg and in the control group between 42 and 46 mmHg and this was confirmed by arterial blood gas measurements taken during the operation. Measuring the brightness and shadows of digital photos Digital color meter was used in MacOS X as a computer software., Results: The mean ratio of periorbital ecchymosis to forehead brightness was 0.84 ± 0.05 in the study group and 0.81 ± 0.03 in the control group. There was no significant difference between the study and control groups ( P  > .05)., Conclusion: This study investigates the potential role of hypocapnia on postoperative ecchymosis during rhinoplasty. The severity of ecchymosis was less in the patients with induced mild hypocapnia regarding both subjective and objective evaluations, but this difference didn't reach statistical significance compared to the normocapnic control group.

Aims: Acute heart failure (AHF) poses a major threat to hospitalized patients for its high mortality rate and serious complications. The aim of this study is to determine whether hypocapnia [defined as the partial pressure of arterial carbon dioxide (PaCO 2 ) below 35 mmHg] on admission could be associated with in-hospital all-cause mortality in AHF., Methods and Results: A total of 676 patients treated in the coronary care unit for AHF were retrospectively analysed, and the study endpoint was in-hospital all-cause mortality. The 1:1 propensity score matching (PSM) analysis, Kaplan-Meier curve, and Cox regression model were used to explore the association between hypocapnia and in-hospital all-cause mortality in AHF. Receiver operating characteristic (ROC) curve and Delong's test were used to assess the performance of hypocapnia in predicting in-hospital all-cause mortality in AHF. The study cohort included 464 (68.6%) males and 212 (31.4%) females, and the median age was 66 years (interquartile range 56-74 years). Ninety-eight (14.5%) patients died during hospitalization and presented more hypocapnia than survivors (76.5% vs. 45.5%, P < 0.001). A 1:1 PSM was performed between hypocapnic and non-hypocapnic patients, with 264 individuals in each of the two groups after matching. Compared with non-hypocapnic patients, in-hospital mortality was significantly higher in hypocapnic patients both before (22.2% vs. 6.8%, P < 0.001) and after (20.8% vs. 8.7%, P < 0.001) PSM. Kaplan-Meier curve showed a significantly higher probability of in-hospital death in patients with hypocapnia before and after PSM (both P < 0.001 for the log-rank test). Multivariate Cox regression analysis showed that hypocapnia was an independent predictor of AHF mortality both before [hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.23-3.98; P = 0.008] and after (HR 2.19; 95% CI 1.18-4.07; P = 0.013) PSM. Delong's test showed that the area under the ROC curve was improved after adding hypocapnia into the model (0.872, 95% CI 0.839-0.901 vs. 0.855, 95% CI 0.820-0.886, P = 0.028). PaCO 2 was correlated with the estimated glomerular filtration rate (r = 0.20, P = 0.001), left ventricular ejection fraction (r = 0.13, P < 0.001), B-type natriuretic peptide (r = -0.28, P < 0.001), and lactate (r = -0.15, P < 0.001). Kaplan-Meier curve of PaCO 2 tertiles and multivariate Cox regression analysis showed that the lowest PaCO 2 tertile was associated with increased risk of in-hospital mortality in AHF (all P < 0.05)., Conclusions: Hypocapnia is an independent predictor of in-hospital mortality for AHF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Central sleep apnea is not a single disorder; it can present as an isolated disorder or as a part of other clinical syndromes. In some conditions, such as heart failure, central apneic events are due to transient inhibition of ventilatory motor output during sleep, owing to the overlapping influences of sleep and hypocapnia. Specifically, the sleep state is associated with removal of wakefulness drive to breathe; thus, rendering ventilatory motor output dependent on the metabolic ventilatory control system, principally PaCO2. Accordingly, central apnea occurs when PaCO2 is reduced below the "apneic threshold". Our understanding of the pathophysiology of central sleep apnea has evolved appreciably over the past decade; accordingly, in disorders such as heart failure, central apnea is viewed as a form of breathing instability, manifesting as recurrent cycles of apnea/hypopnea, alternating with hyperpnea. In other words, ventilatory control operates as a negative-feedback closed-loop system to maintain homeostasis of blood gas tensions within a relatively narrow physiologic range, principally PaCO2. Therefore, many authors have adopted the engineering concept of "loop gain" (LG) as a measure of ventilatory instability and susceptibility to central apnea. Increased LG promotes breathing instabilities in a number of medical disorders. In some other conditions, such as with use of opioids, central apnea occurs due to inhibition of rhythm generation within the brainstem. This review will address the pathogenesis, pathophysiologic classification, and the multitude of clinical conditions that are associated with central apnea, and highlight areas of uncertainty., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this research was to examine the prevalence of hyperventilation (defined by pCO 2 value) among acute heart failure (AHF) patients and to link it with potential triggers and prognosis. All patients underwent dyspnea severity assessment and capillary blood examination on hospital admission and during hospitalization. Out of 241 AHF patients, 57(24%) were assigned to low pCO 2 group (pCO 2  ≤ 30 mmHg) and 184 (76%) to normal pCO 2 group (pCO 2  > 30 mmHg). Low pCO 2 group had significantly lower HCO 3 - (22.3 ± 3.4 vs 24.7 ± 2.9 mmol/L, p < 0.0001) and significantly higher lactate level (2.53 ± 1.6 vs 2.14 ± 0.97 mmol/L, p = 0.03). No differences between groups were observed in respect to the following potential triggers of hyperventilation: hypoxia (sO 2 92.5 ± 5.2 vs 92 ± 5.6% p = 0.57), infection (CRP 10.5[4.9-26.4]vs 7.15[3.45-17.35] mg/L, p = 0.47), dyspnea severity (7.8 ± 2.3vs 8.0 ± 2.3 points, p = 0.59) and pulmonary congestion (82.5 vs 89.1%, p = 0.19), respectively. Low pCO 2 value was related to an increased 4-year all-cause mortality hazard ratio (HR) (95% CI) 2.2 (1.3-3.6); p = 0.002 and risk of death and of rehospitalization for HF, HR (95% CI) 2.0 (1.3-3.0); p = 0.002. Hyperventilation is relatively frequent in AHF and is related to poor prognosis. Low pCO 2 was not contingent on expected potential triggers of dyspnea but rather on tissue hypoperfusion., (© 2022. The Author(s).)

Objective: To evaluate the association between hypocapnia within the first 24 h of life and brain injury assessed by a detailed MRI scoring system in infants receiving therapeutic hypothermia (TH) for neonatal encephalopathy (NE) stratified by the stage of NE., Study Design: This retrospective cohort study included infants who received TH for mild to severe NE., Results: 188 infants were included in the study with 48% having mild and 52% moderate-severe NE. Infants with moderate-severe NE spent more time in hypocapnia (PCO 2  ≤ 35 mmHg) and presented with more severe brain injury on MRI compared to mild cases. The MRI injury score increased by 6% for each extra hour spent in hypocapnic range in infants with moderate-severe NE. There was no association between hypocapnia and injury scores in mild cases., Conclusion: In infants with moderate-severe NE, the hours spent in hypocapnia was an independent predictor of brain injury., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Pulmonary arterial hypertension (PAH) is a rare dyspnoea-fatigue syndrome caused by a progressive increase in pulmonary vascular resistance and eventual right ventricular (RV) failure. In spite of extensive pulmonary vascular remodelling, lung function in PAH is generally well preserved, with hyperventilation and increased physiological dead space, but minimal changes in lung mechanics and only mild to moderate hypoxaemia and hypocapnia. Hypoxaemia is mainly caused by a low mixed venous oxygen tension from a decreased cardiac output. Hypocapnia is mainly caused by an increased chemosensitivity. Exercise limitation in PAH is cardiovascular rather than ventilatory or muscular. The extent of pulmonary vascular disease in PAH is defined by multipoint pulmonary vascular pressure-flow relationships with a correction for haematocrit. Pulsatile pulmonary vascular pressure-flow relationships in PAH allow for the assessment of RV hydraulic load. This analysis is possible either in the frequency domain or in the time domain. The RV in PAH adapts to increased afterload by an increased contractility to preserve its coupling to the pulmonary circulation. When this homeometric mechanism is exhausted, the RV dilates to preserve flow output by an additional heterometric mechanism. Right heart failure is then diagnosed by imaging of increased right heart dimensions and clinical systemic congestion signs and symptoms. The coupling of the RV to the pulmonary circulation is assessed by the ratio of end-systolic to arterial elastances, but these measurements are difficult. Simplified estimates of RV-pulmonary artery coupling can be obtained by magnetic resonance or echocardiographic imaging of ejection fraction., Competing Interests: Conflicts of interest: R. Naeije reports relationships including consultancies, speaker fees and membership of advisory boards with AOP Orphan Pharmaceuticals, Johnson & Johnson, Lung Biotechnology Corporation and United Therapeutics. Conflicts of interest: M.J. Richter has received funding from the German Research Foundation (DFG, 413584448) and from the Collaborative Research Center (SFB) 1213 – Pulmonary Hypertension and Cor Pulmonale (grant number SFB1213/1, project B08; German Research Foundation, Bonn, Germany). Conflicts of interest: L.J. Rubin reports consultancies with Actelion, SoniVie, Gossamer Bio and Bellerophon., (Copyright ©The authors 2022.)

BACKGROUND: Physiological episodes are a top safety concern for aviators across the United States military. While many cases and a variety of causes for physiological episodes have been described, few cases, if any, have been reported of hyperventilation-induced hypocapnia and transient loss of consciousness. CASE REPORT: Here we describe a case of an aviator who experienced tingling extremities, confusion, and loss of consciousness during a flight. The aviator incorrectly believed he was experiencing hypoxia and continued to take multiple steps to troubleshoot the wrong underlying problem for his symptoms. Evaluation after landing suggested this was instead a stress-induced hyperventilation that resulted in symptomatic hypocapnia. DISCUSSION: We report this case to add to the body of literature in understanding this phenomenon as well as to provide aviators, physiologists, and flight surgeons with practical suggestions for recognizing hyperventilation-induced hypocapnia and awareness of how to remedy this situation when they recognize it. Kramer KEP, Anderson EE. Hyperventilation-induced hypocapnia in an aviator . Aerosp Med Hum Perform. 2022; 93(5):470-471.

Purpose: In laparoscopic surgery (LS) for colorectal cancer (CRC), the relationship between intraoperative end-tidal carbon dioxide concentration (EtCO 2 ) and surgery-related complications remains unexplored. This study assessed the impact of intraoperative EtCO 2 on postoperative complications in LS for CRC., Methods: In total, 909 patients who underwent LS for CRC were enrolled. Hypocapnia and hypercapnia were defined as EtCO 2  < 35 mmHg and > 40 mmHg, respectively, and the relationships between hypocapnia or hypercapnia duration and postoperative complications were analyzed., Results: The median (range) durations of hypocapnia and hypercapnia were 2.0 (0-8.3) h and 0.3 (0-5.8) h, respectively. Complications were observed in 208 cases (23.0%), which included 37 (4.1%) instances of anastomotic leakage and 86 (9.5%) of superficial surgical site infection (SSI). While the hypercapnia duration was not associated with the short-term outcomes, prolonged hypocapnia was significantly correlated with complications (p = 0.02), specifically superficial SSI (p = 0.005). Multivariate analyses adjusted for confounding factors confirmed that hypocapnia prolongation was an independent risk factor for postoperative superficial SSI [OR 1.19; 95% confidence interval (Cl) 1.03-1.36, p = 0.01]., Conclusion: Intraoperative hypocapnia may be a risk factor for postoperative complications, in particular superficial SSI, in LS for CRC., (© 2021. Springer Nature Singapore Pte Ltd.)

Background: The hyperventilation syndrome (HVS) is characterized by somatic/ psychological symptoms due to sustained hypocapnia and respiratory alkalosis without any organic disease., Objective: The purpose of this study was to compare ventilatory parameters and symptoms reproducibility during the hyperventilation provocation test (HVPT) and cardiopulmonary exercise test (CPET) as diagnostic tools in patients with HVS, and to identify the most frequent etiologies of the HVS by a systematic assessment., Methods: After exclusion of organic causes, 59 patients with HVS according to Nijmegen's questionnaire (NQ) score ≥23 with associated hypocapnia (PaCO 2 /PET CO2 <35 mm Hg) were studied., Results: The most frequent comorbidities of HVS were anxiety and asthma (respectively 95% and 73% of patients). All patients described ≥3 symptoms of NQ during the HVPT vs 14% of patients during the CPET (p<0.01). For similar maximal ventilation (61 L/min during HVPT vs 60 L/min during CPET), the median level of PET CO2  decreased from 30 mmHg at baseline to 15 mmHg during hyperventilation and increased from 31 mmHg at baseline to 34 mmHg at peak exercise (all p<0.01). No significant difference for the ventilatory parameters was found between patients with HVS (n = 16) and patients with HVS + asthma (n = 43)., Conclusions: In term of symptoms reproducibility, HVPT is a better diagnostic tool than CPET for HVS. An important proportion of patients with HVS has an atypical asthma previously misdiagnosed. The exercise-induced hyperventilation did not induce abnormal reduction in PET CO2 , suggesting that the exercise could be a therapeutic tool in HVS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA., Methods: Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery., Results: Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001)., Conclusion: S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported.

Purpose: Carbon dioxide (CO 2 ) is a potent cerebral vasomotor agent. Despite reduction in CO 2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO 2 values in acute stroke. The aim of the study was to systematically assess CO 2 levels in acute stroke., Material and Methods: Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO 2 (PaCO 2 ) and end-tidal CO 2 (EtCO 2 ) in acute stroke., Results: After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO 2 levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients., Conclusion: The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO 2 assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Therapeutic hypothermia is the standard treatment for asphyxiated newborns. Since hypocapnia is common in these newborns, the aim of this study was to assess the association among hypocapnia, ventilation, and brain injury., Methods: We conducted a retrospective cohort study of all asphyxiated newborns treated with hypothermia from 2008 to 2014. Partial pressure of carbon dioxide (pCO 2 ), ventilatory status, and modes of ventilation were recorded during the first 4 days of life. Brain injury was evaluated using brain magnetic resonance imaging. Differences between intubated and nonintubated newborns and between the newborns who developed brain injury or not were assessed., Results: One hundred ninety-eight asphyxiated newborns were treated with hypothermia. During the first 2 days of life, intubated newborns had consistently lower pCO 2 levels (respectively, 29.01 ± 8.55, p < .001 on day 1 of life and 33.65 ± 7.12, p = .004 on day 2 of life). Fifty-nine percent of the intubated newborns developed brain injury versus only 43% of the nonintubated newborns (p = .046). The lowest pCO 2 levels averaged over the first 4 days of life were significantly decreased in newborns developing brain injury (p = .02) and significantly associated with brain injury severity (p = .01). After adjusting for potential cofounders, the lowest pCO 2 averaged over days 1-4 of life remained significantly associated with an increased risk of brain injury (odds ratio [95%CI]: 1.07 [1.00-1.14]; p = .04)., Conclusions: Intubated and ventilated asphyxiated newborns experienced more severe hypocapnia, and had higher incidences of brain injury. Hypocapnia during the first 4 days of life was associated with an increased risk of developing (more severe) brain injury.

Objective: Capnography is a key monitoring intervention in several neurologically vulnerable clinical states. Cerebral autoregulation (CA) describes the ability of the cerebrovascular system to maintain a near constant cerebral blood flow throughout fluctuations in systemic arterial blood pressure, with the partial pressure of arterial carbon dioxide known to directly influence CA. Previous work has demonstrated dysautoregulation lasting around 30 s prior to the anticipated augmentation of hyperventilation-associated hypocapnia. In order assess to potential benefit of hypocapnic interventions in an acute stroke setting, minimisation of dysregulation is paramount., Approach: Hyperventilation strategies to induce and maintain hypocapnia were performed in 61 healthy participants, effects on temporal estimates of dynamic cerebral autoregulation (autoregulation index, ARI) were assessed to validate the most effective strategy for inducing and maintaining hypocapnia., Main Results: The extent of initial decrease was significantly smaller in the continuous metronome strategy compared to the delayed metronome and voluntary strategies (▵ARI 0.33  ±  1.18, 2.80  ±  3.33 and 3.69  ±  2.79 respectively, p   <  0.017)., Significance: The use of a continuous metronome to induce hypocapnia rather than the sudden inception of an auditory stimulus appears to reduce the initial decrease in autoregulatory capacity seen in previous studies. Dysautoregulation can be minimised by continuous metronome use during hyperventilation-induced hypocapnia. This advancement in understanding of the behaviour of CA during hypocapnia permits safer delivery of CA targeted interventions, particularly in neurologically vulnerable patient populations.

The objective of the study was to identify markers of hypocapnic cerebral hypoperfusion (HYCH) in patients with orthostatic intolerance (OI) without tachycardia and without orthostatic hypotension. This single center, retrospective study included OI patients referred for autonomic evaluation with the 10 min tilt test. Heart rate, end-tidal CO2 (ET-CO2), blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery were monitored. HYCH was defined by: (1) Symptoms of OI; (2) Orthostatic hypocapnia (low ET-CO2); (3) Abnormal decline in orthostatic CBFv due to hypocapnia; 4) Absence of tachycardia, orthostatic hypotension, or other causes of low CBFv or hypocapnia. Sixteen subjects met HYCH criteria (15/1 women/men, age 38.5±8.0 years) and were matched by age and gender to postural tachycardia patients (POTS, n = 16) and healthy controls (n = 16). During the tilt, CBFv decreased more in HYCH (-22.4±7.7%, p<0.0001) and POTS (-19.0±10.3%, p<0.0001) compared to controls (-3.0±5.0%). Orthostatic ET-CO2 was lower in HYCH (26.4±4.2 (mmHg), p<0.0001) and POTS (28.6±4.3, p<0.0001) compared to controls (36.9 ± 2.1 mmHg). Orthostatic heart rate was normal in HYCH (89.0±10.9 (BPM), p<0.08) and controls (80.8 ±11.2), but was higher in POTS (123.7±11.2, p<0.0001). Blood pressure was normal and similar in all groups. It is concluded that both HYCH and POTS patients have comparable decrease in CBFv which is due to vasoconstrictive effect of hypocapnia. Blood flow velocity monitoring can provide an objective biomarker for HYCH in OI patients without tachycardia., Competing Interests: The author has declared that no competing interests exist.

Background: Dyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients and its association to neurological outcome is undetermined., Methods: This is an exploratory post-hoc substudy of the Target Temperature Management (TTM) trial, including resuscitated OHCA patients, investigating the association between serial measurements of arterial partial carbon dioxide pressure (PaCO 2 ) and neurological outcome at 6 months, defined by the Cerebral Performance Category (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3-5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO 2 and absolute PaCO 2 difference were analyzed. Additionally, the association between mild hypercapnia (6.0-7.30 kPa) and neurological outcome, its interaction with target temperature (33 °C and 36 °C), and the association between PaCO 2 and peak serum-Tau were evaluated., Results: Of the 939 patients in the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients were exposed to hypocapnia or hypercapnia. None of the analyses indicated a statistical significant association between PaCO 2 and neurological outcome (P = 0.13-0.96). Mild hypercapnia was not associated with neurological outcome (P = 0.78) and there was no statistically significant interaction with target temperature (P interaction  = 0.95). There was no association between PaCO 2 and peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC)., Conclusions: Dyscarbia is common after ROSC. No statistically significant association between PaCO 2 in the post-cardiac arrest phase and neurological outcome at 6 months after cardiac arrest was detected. There was no significant interaction between mild hypercapnia and temperature in relation to neurological outcome.

Background: Permissive hypercapnia is a lung-protection strategy. We sought to review our current clinical practice for the range of permissive hypercapnia and identify the relationship between P aCO 2 and pH and adverse outcomes., Methods: A secondary analysis of a delayed cord-clamping clinical trial was performed on all arterial blood gas tests in the first 72 h in infants < 32 weeks gestational age. All arterial blood gas values were categorized into a clinical range to determine the percent likelihood of occurring in the total sample. The univariate and multivariate relationships of severe adverse events and the time-weighted P aCO 2 , fluctuation of P aCO 2 , maximal and minimal P aCO 2 , base excess, and pH were assessed., Results: 147 infants with birthweight of 1,206 ± 395 g and gestational age of 28 ± 2 weeks were included. Of the 1,316 total samples, < 2% had hypocapnia (P aCO 2 <30 mm Hg), 47% were normocapnic (P aCO 2 35-45 mm Hg), 26.5% had mild hypercapnia (P aCO 2 45-55 mm Hg), 13% had moderate hypercapnia (P aCO 2 55-65 mm Hg), and 6.5% had severe hypercapnia (P aCO 2 ≥ 65 mm Hg). There were no adverse events associated with hypocapnia. Subjects with death/severe intraventricular hemorrhage had a higher mean P aCO 2 of 52.3 versus 44.7 (odds ratio [OR] 1.16, 95% CI 1.04-1.29, P = .006), higher variability of P aCO 2 with a standard deviation of 12.6 versus 7.8 (OR 1.15, 95% CI 1.03-1.27, P = .01), and a lower minimum pH of 7.03 versus 7.23 (OR 0, 95% CI 0-0.06, P = .003). There was no significant difference in any variables in subjects who developed other adverse events., Conclusion: The routine targeting of higher than normal P aCO 2 goals may lead to a low incidence of hypocapnia and associated adverse events. Hypercapnia is common, and moderate hypercapnia may increase the risk of neurologic injury and provide little pulmonary benefit., (Copyright © 2018 by Daedalus Enterprises.)

Oxygen therapy, usually administered by a facemask or nasal cannulae, is the current default treatment of respiratory failure. Since respiration entails intake of oxygen and release of carbon dioxide from tissues as waste product, the notion of administering carbon dioxide in respiratory failure appears counter-intuitive. However, carbon dioxide stimulates the chemosensitive area of the medulla, known as the central respiratory chemoreceptor, which activates the respiratory groups of neurones in the brainstem and stimulates inspiration thereby initiating oxygen intake during normal breathing. This vital initiation of normal breathing is via a reduction in the pH of the cerebrospinal fluid and the medullary interstitial fluid. We hypothesise that in cases of type I respiratory failure in which the P a CO 2 is low, administration of carbon dioxide by inhalation would stimulate the respiratory groups of brainstem neurones and facilitate breathing, which would be of therapeutic value. Preliminary clinical evidence in favour of this hypothesis is presented and we recommend that a formal randomised study be carried out., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Study Objectives: To determine whether arousals that terminate obstructive events in obstructive sleep apnea (OSA) (1) induce hypocapnia and (2) subsequently reduce genioglossus muscle activity following the return to sleep., Methods: Thirty-one untreated patients with OSA slept instrumented with sleep staging electrodes, nasal mask and pneumotachograph, end-tidal CO2 monitoring, and intramuscular genioglossus electrodes. End-tidal CO2 was monitored, and respiratory arousals were assigned an end-arousal CO2 change value (PETCO2 on the last arousal breath minus each individual's wakefulness PETCO2). This change value, in conjunction with the normal sleep related increase in PETCO2, was used to determine whether arousals induced hypocapnia and whether the end-arousal CO2 change was associated with genioglossus muscle activity on the breaths following the return to sleep., Results: Twenty-four participants provided 1137 usable arousals. Mean ± SD end-arousal CO2 change was -0.2 ± 2.4 mm Hg (below wakefulness) indicating hypocapnia typically developed during arousal. Following the return to sleep, genioglossus muscle activity did not fall below prearousal levels and was elevated for the first two breaths. End-arousal CO2 change and genioglossus muscle activity were negatively associated such that a 1 mm Hg decrease in end-arousal CO2 was associated with an ~2% increase in peak and tonic genioglossus muscle activity on the breaths following the return to sleep., Conclusions: Arousal-induced hypocapnia did not result in reduced dilator muscle activity following return to sleep, and thus hypocapnia may not contribute to further obstructions via this mechanism. Elevated dilator muscle activity postarousal is likely driven by non-CO2-related stimuli., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Central sleep apnea and Cheyne-Stokes respiration are commonly observed breathing patterns during sleep in patients with congestive heart failure. Common risk factors are male gender, older age, presence of atrial fibrillation, and daytime hypocapnia. Proposed mechanisms include augmented peripheral and central chemoreceptor sensitivity, which increase ventilator instability during both wakefulness and sleep; diminished cerebrovascular reactivity and increased circulation time, which impair the normal buffering of Paco 2 and hydrogen ions and delay the detection of changes in Paco 2 during sleep; and rostral fluid shifts that predispose to hypocapnia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recent clinical trial research suggests that baseline low end-tidal CO 2 (ETCO 2 , the biological marker of hyperventilation) may predict poorer response to cognitive-behavioral therapy (CBT) for anxiety-related disorders. The present study examined the predictive value of baseline ETCO 2 among patients treated for such disorders in a naturalistic clinical setting. Sixty-nine adults with a primary diagnosis of a DSM-5 anxiety disorder, obsessive-compulsive disorder, or posttraumatic stress disorder completed a 4-min assessment of resting ETCO 2 , and respiration rate (the first minute was analyzed). Lower ETCO 2 was not associated with a diagnosis of panic disorder, and was associated with lower subjective distress ratings on certain measures. Baseline ETCO 2 significantly predicted treatment dropout: those meeting cutoff criteria for hypocapnia were more than twice as likely to drop out of treatment, and ETCO 2 significantly predicted dropout beyond other pre-treatment variables. Weekly measurement suggested that the lower-ETCO 2 patients who dropped out were not responding well to treatment prior to dropout. The present results, along with previous clinical trial data, suggest that lower pre-treatment ETCO 2 is a negative prognostic indicator for CBT for anxiety-related disorders. It is suggested that patients with lower ETCO 2 might benefit from additional intervention that targets respiratory abnormality., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Intact cerebral blood flow (CBF) is essential for cerebral metabolism and function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can lead to severe cerebral damage. This study was designed to assess internal carotid artery blood flow (ICA-BF) during simulated hypovolemia and noninvasive positive pressure ventilation (PPV) in young healthy humans. Beat-by-beat blood velocity (ICA and aorta) were measured by Doppler ultrasound during normovolemia and simulated hypovolemia (lower body negative pressure), with or without PPV in 15 awake subjects. Heart rate, plethysmographic finger arterial pressure, respiratory frequency, and end-tidal CO 2 (ETCO 2 ) were also recorded. Cardiac index (CI) and ICA-BF were calculated beat-by-beat. Medians and 95% confidence intervals and Wilcoxon signed rank test for paired samples were used to test the difference between conditions. Effects on ICA-BF were modeled by linear mixed-effects regression analysis. During spontaneous breathing, ICA-BF was reduced from normovolemia (247, 202-284 mL/min) to hypovolemia (218, 194-271 mL/min). During combined PPV and hypovolemia, ICA-BF decreased by 15% (200, 152-231 mL/min, P = 0.001). Regression analysis attributed this fall to concurrent reductions in CI (β: 43.2, SE: 17.1, P = 0.013) and ETCO 2 (β: 32.8, SE: 9.3, P = 0.001). Mean arterial pressure was maintained and did not contribute to ICA-BF variance. In healthy awake subjects, ICA-BF was significantly reduced during simulated hypovolemia combined with noninvasive PPV Reductions in CI and ETCO 2 had additive effects on ICA-BF reduction. In hypovolemic patients, even low-pressure noninvasive ventilation may cause clinically relevant reductions in CBF, despite maintained arterial blood pressure., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Background: Hypotension (HT) and/or hypocapnia (HC) are frequent complications occurring during pediatric anesthesia and may cause cerebral injury in the developing brain., Aim: The aim of this study is to investigate the effects of HT and/or HC on perfusion and metabolism in the developing brain., Methods: Twenty-eight piglets were randomly allocated to four groups: control (C), HT, HC, and hypotension and hyocapnia (HTC). Anesthesia was induced and maintained using sevoflurane. Fentanyl was added for instrumentation. Piglets were fully monitored and their lungs were artificially ventilated. Before treatment, conventional magnetic resonance imaging (MRI), dynamic susceptibility-contrast-enhanced T2*-weighted MRI (DSC-MRI), and single voxel proton MR spectroscopy ((1) H MRS) were performed. Hypotension (mean arterial blood pressure: 30 ± 3 mmHg) was induced by blood withdrawal and nitroprusside infusion, and hyperventilation was used to induce HC (PaCO2 : 2.7-3.3 kPa). (1) H MRS and DSC-MRI were repeated immediately once treatment goals were achieved and 120 min later. Radiologists were blinded to the groups. DSCI-MRI and (1) H MRS analyses were performed in the thalamus, occipital and parietal lobe, hippocampus, and watershed areas., Results: In comparison to C, mean time to peak (TTP) increased with HTC in all brain areas as assessed with DSC-MRI (n = 26). Using (1) H MRS, a significant decrease in N-acetyl aspartate, choline, and myoinositol, as well as an increase in glutamine-glutamate complex (Glx) were detected independent of group. Compared to C, changes were more pronounced for Glx (due to an increase in glutamate) and myoinositol with HTC, for N-acetyl aspartate with HT, and for Glx with HC. No lactate signal was present., Conclusions: The combination of HT and HC during sevoflurane anesthesia resulted in alteration of cerebral perfusion with signs of neuronal dysfunction and early neuronal ischemia. HT and HC alone also resulted in signs of metabolic disturbances despite the absence of detectable cerebral perfusion alterations., (© 2016 John Wiley & Sons Ltd.)

Background: Abnormal PCO2 is common in infants with hypoxic ischemic encephalopathy (HIE). The objective was to determine whether hypocapnia was independently associated with unfavorable outcome (death or severe neurodevelopmental disability at 18 mo) in infants with moderate-to-severe HIE., Methods: This was a post hoc analysis of the CoolCap Study in which infants were randomized to head cooling or standard care. Blood gases were measured at prespecified times after randomization. PCO2 and follow-up data were available for 196 of 234 infants. Analyses were performed to investigate the relationship between hypocapnia in the first 72 h after randomization and unfavorable outcome., Results: After adjusting for pH, amplitude-integrated electroencephalogram background and seizures, birth weight, Apgar score at 5 min, cooling status, and Sarnat stage, PCO2 was inversely associated with unfavorable outcome (P < 0.001). The probability of unfavorable outcome was 0.20 ± 0.1 (point estimate ± SE), 0.53 ± 0.23 and 0.89 ± 0.16 for a PCO2 of 40, 30, and 20 mm Hg respectively and was greater in infants with severe HIE than with moderate HIE., Conclusions: Hypocapnia in infants with moderate-to-severe HIE was independently associated with unfavorable outcome. Future studies of controlled normocapnia will be important.

Objective: Hyperventilation-induced hypocapnia leads to cerebral vasoconstriction and hypoperfusion. Intubated patients are often inadvertently hyperventilated during resuscitations, causing theoretical risk for ischemic brain injury. Current emergency department monitoring systems do not detect these changes. The purpose of this study was to determine if cerebral oximetry (rcSo2) with blood volume index (CBVI) would detect hypocapnia-induced cerebral tissue hypoxia and hypoperfusion., Methods: Patients requiring mechanical ventilation underwent end-tidal CO2 (ETco2), rcSo2, and CBVI monitoring. Baseline data was analyzed and then the effect of varying ETco2 on rcSo2 and CBVI readings was analyzed. Median rcSo2 and CBVI values were compared when above and below the ETco2 30 mmHg threshold. Subgroup analysis and descriptive statistics were also calculated., Results: Thirty-two patients with neurologic emergencies and potential increased intracranial pressure were included. Age ranged from 6 days to 15 years (mean age, 3.1 years; SD, 3.9 years; median age, 1.5 years: 0.46-4.94 years). Diagnoses included bacterial meningitis, viral meningitis, and seizures. ETco2 crossed 30 mm Hg 80 times. Median left and right rcSO2 when ETCO2 was below 30 mmhg was 40.98 (35.3, 45.04) and 39.84 (34.64, 41) respectively. Median left and right CBVI when ETCO2 was below 30 mmhg was -24.86 (-29.92, -19.71) and -22.74 (-27.23, - 13.55) respectively. Median left and right CBVI when ETCO2 was below 30 mmHg was -24.86 (-29.92, -19.71) and -22.74 (-27.23, -13.55) respectively. Median left and right rcSO2 when ETCO2 was above 30 mmHg was 63.53 (61.41, 66.92) and 63.95 (60.23, 67.58) respectively. Median left and right CBVI when ETCO2 was above 30 mmHg was 12.26 (0.97, 20.16) and 8.11 (-0.2, 21.09) respectively. Median duration ETco2 was below 30 mmHg was 17.9 minutes (11.4, 26.59). Each time ETco2 fell below the threshold, there was a significant decrease in rcSo2 and CBVI consistent with decreased cerebral blood flow. While left and right rcSO2 and CBVI decreased quickly once ETCO2​ was below 30 mmHg, increase once ETCO2​ was above 30 mmHg was much slower., Conclusion: This preliminary study has demonstrated the ability of rcSo2 with CBVI to noninvasively detect the real-time effects of excessive hyperventilation producing ETco2 < 30 mmHg on cerebral physiology in an emergency department. We have demonstrated in patients with suspected increased intracranial pressure that ETco2 < 30 mmHg causes a significant decrease in cerebral blood flow and regional tissue oxygenation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Hypocarbia during the first 12 h of life is associated with mortality and disability in neonatal hypoxic ischemic encephalopathy (HIE). Notable variation in arterial carbon dioxide tension (PaCO2) during the first 4 d of life is related to severe intraventricular hemorrhages in preterm infants. We examined the association between PaCO2 during 72 h of whole-body therapeutic hypothermia for neonatal HIE and 2-year neurodevelopmental outcomes., Methods: A retrospective review of 23 term neonates treated with whole-body hypothermia documented clinical, demographic and arterial blood gas data. Comparisons were made across good and severe neurodevelopmental outcome groups at 2 years of age., Results: Severe neurodevelopmental outcomes were documented in 8 of 23 toddlers. There were no significant differences between outcome groups with regard to the number of patients with hypocarbic means or measurements. There were also no significant differences with mean PaCO2, PaO2, pH, time-weighted cumulative hypocarbia, and PaCO2 range. The severe neurodevelopmental outcomes group had a significantly higher mean PaCO2 standard deviation (p = 0.04; 95% CI, -5.46 to -0.39)., Conclusion: Severe neurodevelopmental outcomes were significantly associated with high PaCO2 variability over 72 h in whole-body-cooled HIE neonates. Mitigating these fluctuations may be a potential management strategy.

Lactic acidosis is a recognized event in adult patients with acute severe asthma (ASA). Only a few cases have been reported in children. Hereinafter is reported the case of a 2-year-old girl hospitalized in the pediatric intensive care unit for ASA, which was treated with high-flow oxygen therapy and intravenous methylprednisolone and salbutamol. During hospitalization, she had metabolic acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to 12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The work-up for a congenital metabolic disease was normal. Progression was propitious with spontaneous improvement of lactic acidosis, and the child was discharged from the intensive care unit after 72 h. The origin of lactic acidosis during ASA seems to be multifactorial. Although its recovery can be spontaneous, it is important to know how to identify it because it can worsen respiratory symptoms and can lead to incongruous therapeutic escalation., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The purpose of this study is to determine whether hyperthermia-induced hyperventilation with subsequent hypocapnia is relevant to febrile seizures in children. This is only the second study to measure pCO2 and pH values in children with febrile seizures. This prospective case-control study enrolled 18 children who presented with febrile seizures and 18 children who presented with a febrile illness without seizures. Venous blood gas analyses were measured both from the febrile seizure and control group. There was no significant difference in mean blood pH between the febrile seizure and control groups but blood pCO2 was significantly lower in the febrile seizure group. Patients with complex febrile seizures exhibited significantly lower pCO2 levels within 1 hour of seizure onset than patients with simplex febrile seizures. These data indicate that febrile seizures may be associated with hyperventilation and that the ensuing hypocapnia may contribute to the development of febrile seizures.

Purpose: Current Brain Trauma Foundation guidelines recommend avoiding hypoxemia after severe pediatric traumatic brain injury (TBI). Yet, recent studies on optimum admission oxygenation and ventilation parameters associated with discharge survival in pediatric TBI are lacking., Materials and Methods: After IRB approval, a retrospective study involving pediatric patients ages ≤14 years with severe TBI (head Abbreviated Injury Scale (AIS) score of ≥3, Glasgow Coma Scale score of ≤8 on admission) admitted to Harborview Medical Center (level 1 pediatric trauma center), Seattle, WA, during 2003 to 2007 was performed. Admission demographics, clinical data, and laboratory characteristics were abstracted. Hypoxemia was defined as PaO2 < 60 mmHg, hypocarbia was defined as PaCO2 ≤ 35 mmHg, and hypercarbia was defined as PaCO2 ≥ 46 mmHg., Results: One hundred ninety-four patients met inclusion criteria of which 162 (83.5 %) patients survived. Admission hypoxemia occurred in nine (5.6 %) patients who survived and eight (25 %) patients who died (p < 0.001). Children with admission PaCO2 between 36 and 45 mmHg had greater discharge survival compared with those with both admission hypocarbia (PaCO2 ≤ 35 mmHg) and hypercarbia (PaCO2 ≥ 46 mmHg). Admission PaO2 301-500 mmHg (adjusted odds ratio (AOR), 8.02 (95 % confidence interval (CI), 1.73-37.10); p = 0.008) and admission PaCO2 = 36-45 mmHg (AOR, 5.47 (95 % CI, 1.30-23.07); p = 0.02) were independently associated with discharge survival., Conclusions: Discharge survival after severe pediatric TBI was associated with admission PaO2 301-500 mmHg and PaCO2 = 36-45 mmHg. Admission hypocarbia and hypercarbia were each associated with increased discharge mortality.

Unpressurized aircraft routinely operate at altitudes where hypoxia may be of concern. A systematic literature review was conducted regarding hypoxic impairment, including mental functions, sensory deficits, and other pertinent research findings that may affect aviation-related duties at moderate altitude (8000 to 15,000 ft/2438 to 4572 m). The results of this review suggest that cognitive and psychomotor deficits may include learning, reaction time, decision-making, and certain types of memory. However, results are difficult to quantify and reliably reproduce. Inconsistency of results may be related to the subtlety of deficits compared to high altitude, differences among individual compensatory mechanisms, variation in methodology or sensitivity of metrics, presence or absence of exercise, heterogeneous neuronal central nervous system (CNS) response, and interindividual variation. Literature regarding hypoxic visual decrements is more consistent. Rod photoreceptors are more susceptible to hypoxia; visual degradation has been demonstrated at 4000 to 5000 ft (1219 to 1524 m) under scotopic and 10,000 ft (3048 m) under photopic conditions. Augmented night vision goggle resolution demonstrates more resilience to mild hypoxic effects than the unaided eye under starlight conditions. Hypocapnia enhances visual sensitivity and contrast discrimination. Hyperventilation with resulting respiratory alkalosis and cerebral vasoconstriction may confound both cognitive/ psychomotor and visual experimental results. Future research should include augmentation of validated neuropsychological metrics (surrogate investigational end points) with actual flight metrics, investigation of mixed gas formulations, contribution of hypocapnic vasoconstrictive effects on hypoxic performance, and further investigation into cellular- and systems-level approaches for heterogeneous CNS response. Research is also required into the contribution of mild-moderate hypoxia in human factors- and spatial disorientation-related mishaps.

Background: Septic episodes in preterm infants recently have been reported to be associated with periventricular leukomalacia (PVL). The role of hypocarbia as an independent risk factor for PVL in clinical studies raises many questions without conclusive answers., Aims: To evaluate risk factors for cystic PVL focussing on the influence of hypocarbia., Study Design: Retrospective single centre case-control study., Subjects: Preterm infants 24 to 35 weeks of gestational age and matched (1:2 for gender, birth year, gestational age and birth weight) controls., Outcome Measures: Multivariate analysis of perinatal factors being associated with cystic PVL diagnosed by serial ultrasound examinations., Results: Univariate analysis of risk factors revealed lower 5 and 10 min Apgar scores, and higher rates of neonatal seizures, early-onset sepsis, neonatal steroids, respiratory distress syndrome with surfactant replacement therapy, and episodes of hypocarbia significantly being associated with PVL. Multivariate analysis using a logistic regression model revealed early-onset sepsis and hypocarbia being significantly associated with PVL (p=.022 and .024, respectively). Lowest PaCO(2) values did not differ as did not the duration of hypocarbia, but the onset of hypocarbia was significantly later in PVL cases compared to controls (mean 26 vs. 15 h, p=.033). Neurodevelopmental follow-up at a median time of 46 months was poor showing 88% of the cases having an adverse neurological outcome., Conclusion: We found early-onset sepsis and episodes of hypocarbia within the first days of life being independently associated with PVL., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background/purpose: Although there has been a marked improvement in the survival of children with congenital diaphragmatic hernia (CDH) in the past 2 decades, there are few reports of long-term neurodevelopmental outcome in this population. The present study examined neurodevelopmental outcomes in 10- to 16-year-old CDH survivors not treated with extracorporeal membrane oxygenation (ECMO)., Methods: Parents of 27 CDH survivors completed questionnaires assessing medical problems, daily living skills, educational outcomes, behavioral problems, and executive functioning. Fifteen CDH survivors and matched full-term controls completed standardized intelligence, academic achievement, phonological processing, and working memory tests., Results: Non-ECMO-treated CDH survivors demonstrated high rates of clinically significant difficulties on standardized academic achievement measures, and 14 of the 27 survivors had a formal diagnosis of specific learning disability, attention deficit hyperactivity disorder, or developmental disability. Specific problems with executive function, cognitive and attentional weaknesses, and social difficulties were more common in CDH patients than controls. Perioperative hypocapnia was linked to executive dysfunction, behavioral problems, lowered intelligence, and poor achievement in mathematics., Conclusions: Non-ECMO-treated CDH survivors are at substantial risk for neurodevelopmental problems in late childhood and adolescence., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The etiology of intraventricular hemorrhage (IVH) in very-low-birth-weight (VLBW) infants is multifactorial and is associated with low gestational age (GA) and severity of neonatal respiratory disease. The role of admission hypothermia (AHT) in the pathogenesis of IVH in VLBW infants has not yet been elucidated. We searched risk factors for IVH in VLBW infants while focusing on AHT., Patients and Methods: VLBW infants ≤33 weeks' gestation from three participating medical centers were included. From patients' medical charts we collected variables known to be associated with IVH, focusing on AHT. AHT was defined as rectal temperature ≤35.5°C at admission to the NICU. Head ultrasound was performed at 2-5 and 6-10 days of age and before discharge., Results: 271 VLBW infants were studied. Univariate analysis showed that AHT at ≤35.5°C was not significantly associated with IVH (all grades; p = 0.16), but associated with IVH grade 3-4 (p = 0.034), while AHT at ≤35°C was significantly associated with IVH (p = 0.036) and with IVH grade 3-4 (p = 0.003). Multivariate logistic regression analysis showed that AHT (at ≤35.5 and at ≤35°C) were not associated with IVH. Only four variables were independently significantly associated with IVH: GA, use of nitric oxide, hypocarbia and base deficit >10. Four variables were strongly associated with severe IVH (grades 3-4): GA, hypotension, base deficit >10 and hyponatremia., Conclusions: In VLBW infants, AHT at ≤35.5 and at ≤35.0°C were not significantly associated with IVH. GA, use of nitric oxide, hypocarbia and base deficit >10 were strongly associated with IVH., (Copyright © 2011 S. Karger AG, Basel.)

Sustained or spontaneous hyperventilation has been associated with a variety of physical symptoms and has been linked to a number of organic illnesses and mental disorders. Theories of panic disorder hold that hyperventilation either produces feared symptoms of hypocapnia or protects against feared suffocation symptoms of hypercapnia. Although the evidence for both theories is inconclusive, findings from observational, experimental, and therapeutic studies suggest an important role of low carbon dioxide (CO2) levels in this disorder. Similarly, hypocapnia and associated hyperpnia are linked to bronchoconstriction, symptom exacerbation, and lower quality of life in patients with asthma. Raising CO2 levels by means of therapeutic capnometry has proven beneficial effects in both disorders, and the reversing of hyperventilation has emerged as a potent mediator for reductions in panic symptom severity and treatment success., (2010 Elsevier B.V. All rights reserved.)

Study Objective: To compare the Mapleson D circuit and the bag-valve-mask device for mask ventilation of patients undergoing electroconvulsive therapy (ECT)., Design: Cross-over study., Setting: Single-center academic medical center., Patients: 18 patients undergoing ECT for major depressive disorder., Interventions: Patients were randomized to undergo mask ventilation by the Mapleson D circuit or the bag-valve-mask device., Measurements: End-tidal CO(2), seizure duration, and airway pressure values were recorded., Main Results: End-tidal CO(2) was significantly lower with the bag-valve-mask device. When compared with the bag-valve-mask device, ventilation with the Mapleson circuit resulted in rebreathing of CO(2) in nearly all patients, shorter expiratory time, and lower pressure ramp slope., Conclusions: Hypocapnia was not associated with longer seizures, and the user-device interaction might affect device performance., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: Hypocapnia is used in the management of acute brain injury and may be life-saving in specific circumstances, but it can produce neuronal ischemia and injury, potentially worsening outcome. This review re-examines the rationale for the use of hypocapnia in acute brain injury and evaluates the evidence for therapeutic and deleterious effects in this context., Data Sources and Study Selection: A MEDLINE/PubMed search from 1966 to August 1, 2009, was conducted using the search terms "hyperventilation," "hypocapnia," "alkalosis," "carbon dioxide," "brain," "lung," and "myocardium," alone and in combination. Bibliographies of retrieved articles were also reviewed., Data Extraction and Synthesis: Hypocapnia--often for prolonged periods of time--remains prevalent in the management of severely brain-injured children and adults. Despite this, there is no proof beyond clinical experience with incipient herniation that hypocapnia improves neurologic outcome in any context. On the contrary, hypocapnia can cause or worsen cerebral ischemia. The effect of sustained hypocapnia on cerebral blood flow decreases progressively because of buffering; subsequent normocapnia can cause rebound cerebral hyperemia and increase intracranial pressure. Hypocapnia may also injure other organs. Accidental hypocapnia should always be avoided and prophylactic hypocapnia has no current role., Conclusions: Hypocapnia can cause harm and should be strictly limited to the emergent management of life-threatening intracranial hypertension pending definitive measures or to facilitate intraoperative neurosurgery. When it is used, Paco2 should be normalized as soon as is feasible. Outside these settings hypocapnia is likely to produce more harm than benefit.

Background: The Brain Trauma Foundation (BTF) Guidelines for prehospital management of traumatic brain injury (TBI) recommend a goal end-tidal carbon dioxide of 30 mm Hg to 35 mm Hg in patients without signs of herniation., Methods: We examined prehospital concordance with BTF Guidelines, selected demographic and physiologic variables and outcomes for 100 consecutive admissions to a well-established Level I regional trauma center. All patients had blunt TBI with Glasgow Coma Score < or = 8 without signs of herniation. All were transported by helicopter by flight paramedics experienced with BTF Guidelines and the continuous wave form capnometer. Patients resumed spontaneous ventilation after intubation., Results: Concordance (prehospital end-tidal carbon dioxide > 29 mm Hg) was achieved in 65 of 100 cases. Mortality was 29% (19 of 65) among those in whom guideline levels were achieved prehospital and 46% (16 of 35) in those in whom guideline levels were not achieved prehospital (odds ratio, 0.49; p = 0.10). The "achieved" group was younger (p = 0.02), with higher calculated probability of survival (p = 0.01). Intracranial pressure was maintained under intensive care within acceptable limits in the hospital in both groups but was significantly higher in the "not achieved" group (p = 0.05)., Conclusions: Our data, though not statistically significant, suggest that patients who are harder to keep within the guidelines in the field are more likely to die, because of more severe TBI or complication by other factors such as age or injury severity. Whether increased awareness of this phenomenon can improve outcomes is unknown but suggests an approach to future education and research.

The purpose of the study was to examine whether changes in pCO(2) mediate changes in fear of bodily sensation (as indexed by anxiety sensitivity) in a bio-behavioral treatment for panic disorder that targets changes in end-tidal pCO(2). Thirty-five panic patients underwent 4 weeks of capnometry-assisted breathing training targeting respiratory dysregulation. Longitudinal mediation analyses of the changes in fear of bodily symptoms over time demonstrated that pCO(2), but not respiration rate, was a partial mediator of the changes in anxiety sensitivity. Results were supported by cross lag panel analyses, which indicated that earlier pCO(2) levels predicted later levels of anxiety sensitivity, but not vice versa. PCO(2) changes also led to changes in respiration rate, questioning the importance of respiration rate in breathing training. The results provide little support for changes in fear of bodily sensations leading to changes in respiration, but rather suggest that breathing training targeting pCO(2) reduced fear of bodily sensations in panic disorder.

Aim: Determine the prevalence of sensorineural hearing loss (SNHL) and relate this to cumulative exposure to hypoxia, hypocapnia and hypotension. Describe chronic health problems among 5- to 11-year-old children treated for persistent pulmonary hypertension of the newborn (PPHN)., Methods: The index group consisted of 85 children and a reference group was matched for age, sex and municipality of current residence. Questionnaires were sent to the families. The families in the index group were asked to participate in an examination of their child's hearing., Results: Seven children (11%) had SNHL. SNHL was not associated with hypoxia, hypocapnia or hypotension during treatment for PPHN. In the index group chronic health problems were reported in 42% compared with 17% in the reference group (chi-square test, p = 0.001). Twenty-one percent in the index group were treated with bronchodilator therapy compared with 8% in the reference group (chi-square test, p = 0.028). In the index group five children had cerebral palsy and two had developmental delay. Nineteen percent in the index group and 5% in the reference group had remedial education (chi-square test, p = 0.008)., Conclusion: Children treated for PPHN are at high risk for SNHL. Exposure to hypoxia, hypocapnia or hypotension did not predict SNHL. The incidence of chronic health problems and use of remedial education was high.

Lung injury in ventilated premature infants occurs primarily through the mechanism of volutrauma, often due to the combination of high tidal volumes in association with a high end-inspiratory volume and occasionally end-expiratory alveolar collapse. Tolerating a higher level of arterial partial pressure of carbon dioxide (PaCO2) is considered as 'permissive hypercapnia' and when combined with the use of low tidal volumes may reduce volutrauma and lead to improved pulmonary outcomes. Permissive hypercapnia may also protect against hypocapnia-induced brain hypoperfusion and subsequent periventricular leukomalacia. However, extreme hypercapnia may be associated with an increased risk of intracranial hemorrhage. It may therefore be important to avoid large fluctuations in PaCO2 values. Recent randomized clinical trials in preterm infants have demonstrated that mild permissive hypercapnia is safe, but clinical benefits are modest. The optimal PaCO2 goal in clinical practice has not been determined, and the available evidence does not currently support a general recommendation for permissive hypercapnia in preterm infants.

Purpose: Systemic alkalinization is recommended for resuscitation from local anesthetic-induced cardiotoxicity. It has been suggested that inducing hypocapnic alkalosis, prior to exposure to toxic concentrations of local anesthetics, may minimize cardiotoxicity. However, it remains unclear whether inducing severe hypocapnic alkalosis after administration of local anesthetics will minimize the duration of bradycardia. We used isolated rat hearts to investigate the effects of hypocapnic alkalosis on heart rate (HR) recovery from bupivacaine or levobupivacaine-induced bradycardia., Methods: We measured the time required for the HR in 24 isolated rat hearts, respectively, to attain 90% of the baseline HR (recovery time) following bradycardia induced by 1 microg x mL(-1) and 10 microg x mL(-1) concentrations of either bupivacaine or levobupivacaine. Normal pH perfusate (bupivacaine or levobupivacaine with normal pH washout groups) or severe hypocapnic alkalosis perfusate (bupivacaine or levobupivacaine with hypocapnic alkalosis washout groups) were reperfused after exposure to the local anesthetics., Results: Severe hypocapnic alkalosis prolonged the recovery time from 273 +/- 122 sec, at the 1 microg x mL(-1) bupivacaine concentration with normal pH washout, to 1203 +/- 540 sec, in the bupivacaine with hypocapnic alkalosis washout (p = 0.029). Severe hypocapnic alkalosis also prolonged the recovery time from 1153 +/- 644 sec, at a 10 microg x mL(-1) bupivacaine concentration in the normal pH washout group, to 2065 +/- 617 sec, in the bupivacaine with hypocapnic alkalosis washout group (p = 0.032). With levobupivacaine 10 microg x mL(-1) in the normal pH washout group, HR recovery time increased from 863 +/- 186 sec to 1565 +/- 567 sec, compared to the hypocapnic alkalosis washout group (p = 0.045)., Conclusions: Severe hypocapnic alkalosis prolonged the recovery time from bupivacaine or levobupivacaine-induced bradycardia in isolated rat hearts. When bradycardia occurs after intravascular bupivacaine or levobupivacaine administration, maintenance of normocapnia may minimize the duration of bradycardia.

Objective: To analyse the influence of breathing activity on cerebrovascular dynamics during presyncope., Design: Retrospective study., Setting: University hospital., Patients: 38 subjects developing neurocardiogenic syncope (syncope group), and 61 age-matched control subjects with negative tilt., Interventions: Middle cerebral artery mean blood flow velocity (MCFV), continuous non-invasive blood pressure (BP), end-tidal CO(2) (CO(2)-et) and minute ventilation were measured before and during 45' 60 degrees tilting., Main Outcome Measures: Respiratory and cerebrovascular variability, cerebrovascular resistance (CVR)-absolute and corrected for CO(2)-et at 40 mm Hg (CVR-40)-and dynamic cerebrovascular regulation (CVR-dyn: transfer function phase analysis between MCFV and BP), obtained during supine rest (baseline), first 5 minutes of tilt (early tilt), early- and late presyncope (first and second half, respectively, of 4 minutes preceding syncope in syncope group, and equivalent time in controls)., Results: Tilting induced a mean (SE) CVR decrease in controls (baseline 1.20 (0.04); late presyncope 1.12 (0.06) mm Hg x s/cm, p<0.05) but not in the syncope group (baseline 1.09 (0.04); late presyncope 1.09 (0.06) mm Hg x s/cm, p = NS). However, CVR-40 showed similar reduction in both groups (controls: from 1.15 (0.04) to 0.96 (0.04) mm Hg x s/cm; syncope group: from 1.01 (0.04) to 0.83 (0.04) mm Hg x s/cm, p = NS). CVR-dyn of the two groups was also similar (p = NS). Respiratory variability increased in the syncope group, from early tilt to late presyncope (p<0.05 or better), preceding hyperventilation and being significantly correlated with an increase in MCFV and BP variability (p<0.01)., Conclusions: During presyncope, the development of respiratory instability and hypocapnia impairs MCFV, thus facilitating the onset of syncope despite preserved cerebrovascular regulation.

The purpose of this study was to compare the change in thickness of transversus abdominis (TrA) and internal oblique (IO) muscles, during resting supine respiration, in individuals with lumbopelvic pain (LP) to those who in addition to LP, demonstrate signs of concurrent hypocapnia (LP&HYPO). B-mode ultrasound images were obtained at the height of inspiration, and at the end of expiration, over three subsequent breaths during a single session. The average percent change in thickness of TrA during resting respiration in the LP&HYPO group (20.8+/-7.6%) was found to be statistically greater (P<0.001) than that of the LP only group (1.3+/-5.8%), while the difference between the groups for the percent change in thickness of IO (LP&HYPO 9.2+/-8.1%, LP 2.0+/-7.2%) did not differ (P=0.073). These findings suggest that respiratory modulation of TrA thickness, as measured by ultrasound imaging, greater than 20%, detected in a resting supine position, may be associated with an episode of hypocapnia, and if present warrants further investigation.

Hypocapnia/alkalosis is a consequence of several lung and metabolic pathologies. The aim of this study was to determine whether the increase of fluid filtration rate (FFR) that occurs during Hypocapnia/alkalosis circumstances is determined by hypocapnia, alkalosis or both. 7 groups were formed (N=36) using isolated rabbit lungs. Group 1: Control (PCO2 6%, pH: 7.35-7.45); Group 2 (n=6): Hypocapnia/Alkalosis (CO2 1%, pH: 7.9); Group 3 (n=6): Hypocapnia/Normo-pH (CO2 1% pH 7.35-7.45), Group 4 (n=6) Normocapnia/Alcalosis (CO2 6%, pH: 7.9). Fenoterol, papaverine and hydrocortisone were added to Groups 5, 6 and 7 (n=4) respectively, all under Normocapnia/Alkalosis. FFR and Pulmonary Arterial Pressure (Pap) were considerably higher in group 2 than in control (FFR: 1.92g/min +/- 0.6 vs 0.0 g/min +/- 0.006). A strong influence exerted by pH was observed when Group 3 and group 4 were compared (FFR: 0.02 g/min +/- 0.009 vs 2.3 g/min +/- 0.9) and (Pap: 13.5 cmH2O +/- 1.4 vs 90 cmH2O +/- 15). A reduced effect was observed in groups 5 and 6 (papaverine and hydrocorisone) and a totally abolished effect was observed in group 7 (fenoterol) (FFR: 0.001 +/- 0.0003 mL/min and Pap: 14 +/- 0.8 cmH2O). Pulmonary edema induced by Hypocapnia/alkalosis is a consequence of alkalosis and not of hypocapnia. This effect could be due to inflammatory damage in the lung parenchyma and alkalosis-mediated vasoconstriction.

Central sleep apnea (CSA) is characterized by a lack of drive to inspire for at least 10 sec. In the CSA-syndrome accompanying arousals and desaturations of the arterial blood cause sleep disturbances and sympathetic nerve activations which lead to excessive daytime sleepiness and increase the risk for cardiovascular morbidity. There are six manifestations of CSA: a rare primary or idiopathic form, often in hypocapnic patients with an increased hypercapnic ventilatory drive; Cheyne-Stokes respiration, characterised by periodic CSA and a crescendo/decrescendo breathing pattern, often in patients with severe cardiac or neurological diseases; high altitude-induced periodic breathing (above 4000 m), CSA due to medical or neurological conditions; CSA due to drug or substance use; and primary sleep apnea of infancy. Besides the consequent treatment of the underlying medical conditions therapeutic options include the use of drugs, e. g. acetacolamide or oxygen, as well as non-invasive ventilation, e. g. continuous positive airway pressure (CPAP) or adaptive servo-ventilation.

Objective: To examine the effects of acute maternal hypocapnia and hypercapnia on electronic fetal heart rate (FHR) patterns in late gestation., Methods: Thirty-five women with healthy singleton pregnancies performed a modified carbon dioxide (CO2) rebreathing procedure between 34 and 38 weeks of pregnancy. Prior to rebreathing, subjects hyperventilated for five minutes to reduce end-tidal CO2 tensions (PETco2) below 23 Torr (hypocapnia). During rebreathing, PETco2 progressively increased from hypocapnia to hypercapnia (PETco2 = 40-60 Torr) at a constant hyperoxic end-tidal O2 tension of 150 Torr. FHR responses were classified using standardized guidelines over four periods: 20 minutes before rebreathing (pretest), during hypocapnia and hypercapnia, and 20 minutes after rebreathing (post-test)., Results: Mean baseline FHR measures (SD) over the four test periods were 138(8), 144(10), 132(11), and 137(9) beats per minute (bpm). All pairwise comparisons were statistically significant except the pretest versus post-test comparison (P < 0.05, Tukey-Kramer multiple comparisons test). A single tachycardia episode of 170 bpm was recorded in the post-test period. In 20 subjects FHR variability changed from moderate in the pretest period to minimal during hypocapnia and/or hypercapnia. All but two returned to moderate FHR variability in the post-test period. One other fetus with minimal post-test variability had moderate values in the three preceding test periods., Conclusion: Electronic FHR parameters remained within normal limits for third-trimester fetuses with the exception of one fetus that experienced tachycardia. Acute maternal hypocapnia and hypercapnia over the range studied had no adverse effects on fetal well-being. These results support the safety of the modified CO2 rebreathing procedure for research in healthy, low-risk pregnancy.