Clinical practice and effect of carbon dioxide on outcomes in mechanically ventilated acute brain-injured patients: a secondary analysis of the ENIO study.

PURPOSE: The use of arterial partial pressure of carbon dioxide (PaCO2) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We aimed to describe targets for PaCO2 in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO2 values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO2 with in-hospital mortality. METHODS: We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO2 was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO2 > 35 and to 45 mmHg; mild hypocapnia as 32-35 mmHg; severe hypocapnia as 26-31 mmHg, forced hypocapnia as < 26 mmHg, and hypercapnia as > 45 mmHg. RESULTS: 1476 patients (65.9% male, mean age 52 ± 18 years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO2 had a U-shape relationship with in-hospital mortality with only severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus p value = 0.0009). Important differences were observed across different subgroups of ABI patients. CONCLUSIONS: Normocapnia and mild hypocapnia are common in ABI patients and do not affect patients' outcome. Extreme derangements of PaCO2 values were significantly associated with increased in-hospital mortality.

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats.

BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

The Effects of Hypocapnia and Hypercapnia on Intraoperative Bleeding, Surgical Field Quality, and Surgeon Satisfaction Level in Septorhinoplasty: A Prospective Randomized Clinical Study.

BACKGROUND: Septorhinoplasty (SRP) is one of the most commonly performed procedures in the world for functional and aesthetic purposes. The present study was aimed to compare the effects of hypocapnia and hypercapnia regarding the total amount of intraoperative bleeding, surgical field quality, and surgeon satisfaction level. METHODS: In this randomized prospective clinical study, eighty patients with American Society of Anesthesiologists I-II and were 18-45 years old scheduled for septorhinoplasty were randomly allocated to group hypocapnia [end-tidal carbon dioxide (EtCO2) 30 ± 2 mmHg] and group hypercapnia (EtCO2 40 ± 2 mmHg). We evaluated the total amount of intraoperative bleeding, the surgical field quality, surgeon satisfaction level, hemodynamics and peri- and postoperative adverse events. RESULTS: Group hypocapnia significantly reduced the total amount of intraoperative bleeding (p < 0.001). The surgical field quality and surgeon satisfaction level in group hypocapnia were significantly better than group hypercapnia (p < 0.001). EtCO2 levels of group hypocapnia were significantly lower than group hypercapnia at all time points (p < 0.001 for all time points). There were no significant differences between the groups in terms of heart rate and mean arterial pressure at all time points. There were no significant differences between the groups in terms of adverse events CONCLUSIONS: The results of this double-blind randomized clinical trial showed that reducing the amount of intraoperative bleeding for patients with hypocapnia undergoing SRP through known methods (e.g., reverse Trendelenburg head-up position, positive end-expiratory pressure limiting, controlled hypotension, and use of topical vasoconstrictors, corticosteroids, and tranexamic acid) would improve the quality of the surgical field and raise the surgeon satisfaction level. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intraoperative partial pressure of arterial carbon dioxide levels and adverse outcomes in patients undergoing lung transplantation.

OBJECTIVE: Patients undergoing lung transplantation (LTx) often experience abnormal hypercapnia or hypocapnia. This study aimed to investigate the association between intraoperative PaCO2 and postoperative adverse outcomes in patients undergoing LTx. METHODS: We retrospectively reviewed the medical records of 151 patients undergoing LTx. Patients' demographics, perioperative clinical factors, and pre- and intraoperative PaCO2 data after reperfusion were collected and analyzed. Based on the PaCO2 levels, patients were classified into three groups: hypocapnia (≤35 mmHg), normocapnia (35.1-55 mmHg), and hypercapnia (>55 mmHg). Univariate and multivariable logistic regressions were used to identify independent risk factors for postoperative composite adverse events and in-hospital mortality. RESULTS: Intraoperative hypercapnia occurred in 69 (45.7%) patients, and hypocapnia in 17 (11.2%). Patients with intraoperative PaCO2 of 35.1-45 mmHg showed a lower incidence of composite adverse events (53.3%) and mortality (6.2%) (P < 0.001). There was no significant difference in composite adverse events and mortality among preoperative PaCO2 groups (P > 0.05). Compared with intraoperative PaCO2 at 35.1-45 mmHg, the risk of composite adverse events in hypercapnia group increased: the adjusted OR was 3.07 (95% confidence interval [CI]: 1.36-6.94; P = 0.007). The risk of death was significantly higher in hypocapnia group than normocapnia group, the adjusted OR was 7.69 (95% CI: 1.68-35.24; P = 0.009). Over ascending ranges of PaCO2, PaCO2 at 55.1-65 mmHg had the strongest association with composite adverse events, the adjusted OR was 6.40 (95% CI: 1.18-34.65; P = 0.031). CONCLUSION: These results demonstrate that intraoperative hypercapnia independently predicts postoperative adverse outcomes in patients undergoing LTx. Intraoperative hypocapnia shows predictive value for postoperative in-hospital mortality in LTx.

Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

Cerebral uptake of microvesicles occurs in normocapnic but not hypocapnic passive hyperthermia in young healthy male adults.

Passive hyperthermia causes cerebral hypoperfusion primarily from heat-induced respiratory alkalosis. However, despite the cerebral hypoperfusion, it is possible that the mild alkalosis might help to attenuate cerebral inflammation. In this study, the cerebral exchange of extracellular vesicles (microvesicles), which are known to elicit pro-inflammatory responses when released in conditions of stress, were examined in hyperthermia with and without respiratory alkalosis. Ten healthy male adults were heated passively, using a warm water-perfused suit, up to core temperature + 2°C. Blood samples were taken from the radial artery and internal jugular bulb. Microvesicle concentrations were determined in platelet-poor plasma via cells expressing CD62E (activated endothelial cells), CD31+ /CD42b- (apoptotic endothelial cells), CD14 (monocytes) and CD45 (pan-leucocytes). Cerebral blood flow was measured via duplex ultrasound of the internal carotid and vertebral arteries to determine cerebral exchange kinetics. From baseline to poikilocapnic (alkalotic) hyperthermia, there was no change in microvesicle concentration from any cell origin measured (P-values all >0.05). However, when blood CO2 tension was normalized to baseline levels in hyperthermia, there was a marked increase in cerebral uptake of microvesicles expressing CD62E (P = 0.028), CD31+ /CD42b- (P = 0.003) and CD14 (P = 0.031) compared with baseline, corresponding to large increases in arterial but not jugular venous concentrations. In a subset of seven participants who underwent hypercapnia and hypocapnia in the absence of heating, there was no change in microvesicle concentrations or cerebral exchange, suggesting that hyperthermia potentiated the CO2 /pH-mediated cerebral uptake of microvesicles. These data provide insight into a potential beneficial role of respiratory alkalosis in heat stress. KEY POINTS: The hyperthermia-induced hyperventilatory response is observed in most humans, despite causing potentially harmful reductions in cerebral blood flow. We tested the hypothesis that the respiratory-induced alkalosis is associated with lower circulating microvesicle concentrations, specifically in the brain, despite the reductions in blood flow. At core temperature + 2°C with respiratory alkalosis, microvesicles derived from endothelial cells, monocytes and leucocytes were at concentrations similar to baseline in the arterial and cerebral venous circulation, with no changes in cross-brain microvesicle kinetics. However, when core temperature was increased by 2°C with CO2 /pH normalized to resting levels, there was a marked cerebral uptake of microvesicles derived from endothelial cells and monocytes. The CO2 /pH-mediated alteration in cerebral microvesicle uptake occurred only in hyperthermia. These new findings suggest that the heat-induced hyperventilatory response might serve a beneficial role by preventing potentially inflammatory microvesicle uptake in the brain.

The effect of oscillatory hemodynamics on the cardiovascular responses to simulated hemorrhage during isocapnia.

During cerebral hypoperfusion induced by lower body negative pressure (LBNP), cerebral tissue oxygenation is protected with oscillatory arterial pressure and cerebral blood flow at low frequencies (0.1 Hz and 0.05 Hz), despite no protection of cerebral blood flow or oxygen delivery. However, hypocapnia induced by LBNP contributes to cerebral blood flow reductions, and may mask potential protective effects of hemodynamic oscillations on cerebral blood flow. We hypothesized that under isocapnic conditions, forced oscillations of arterial pressure and blood flow at 0.1 Hz and 0.05 Hz would attenuate reductions in extra- and intracranial blood flow during simulated hemorrhage using LBNP. Eleven human participants underwent three LBNP profiles: a nonoscillatory condition (0 Hz) and two oscillatory conditions (0.1 Hz and 0.05 Hz). End-tidal (et) CO2 and etO2 were clamped at baseline values using dynamic end-tidal forcing. Cerebral tissue oxygenation (ScO2), internal carotid artery (ICA) blood flow, and middle cerebral artery velocity (MCAv) were measured. With clamped etCO2, neither ICA blood flow (ANOVA P = 0.93) nor MCAv (ANOVA P = 0.36) decreased with LBNP, and these responses did not differ between the three profiles (ICA blood flow: 0 Hz: 2.2 ± 5.4%, 0.1 Hz: -0.4 ± 6.6%, 0.05 Hz: 0.2 ± 4.8%; P = 0.56; MCAv: 0 Hz: -2.3 ± 7.8%, 0.1 Hz: -1.3 ± 6.1%, 0.05 Hz: -3.1 ± 5.0%; P = 0.87). Similarly, ScO2 did not decrease with LBNP (ANOVA P = 0.21) nor differ between the three profiles (0 Hz: -2.6 ± 3.3%, 0.1 Hz: -1.6 ± 1.5%, 0.05 Hz: -0.2 ± 2.8%; P = 0.13). Contrary to our hypothesis, cerebral blood flow and tissue oxygenation were protected during LBNP with isocapnia, regardless of whether hemodynamic oscillations were induced.NEW & NOTEWORTHY We examined the role of forcing oscillations in arterial pressure and blood flow at 0.1 Hz and 0.05 Hz on extra- and intracranial blood flow and cerebral tissue oxygenation during simulated hemorrhage (using lower body negative pressure, LBNP) under isocapnic conditions. Contrary to our hypothesis, both cerebral blood flow and cerebral tissue oxygenation were completely protected during simulated hemorrhage with isocapnia, regardless of whether oscillations in arterial pressure and cerebral blood flow were induced. These findings highlight the protective effect of preventing hypocapnia on cerebral blood flow under simulated hemorrhage conditions.

Relationship between disturbances of CO2 homeostasis and force output characteristics during isometric knee extension.

To determine whether disturbances of CO2 homeostasis alter force output characteristics of lower limb muscles, participants performed four isometric knee extension trials (MVC30 %, 10 s each with 20-s rest intervals) in three CO2 conditions (normocapnia [NORM], hypercapnia [HYPER], and hypocapnia [HYPO]). Respiratory frequency and tidal volume were matched between CO2 conditions. In each MVC30 %, the participants exerted a constant force (30 % of maximum voluntary contraction [MVC]). The force coefficient of variation (Fcv) during each MVC30 % and MVC before and after the four MVC30 % trials were measured. For the means of the four trials, Fcv was significantly lower in HYPER than in HYPO. However, within HYPER, a significant positive correlation was found between the increase in end-tidal CO2 partial pressure and the increase in Fcv. MVCs in NORM and HYPO decreased significantly over the four trials, while no such reduction was observed in HYPER. These results suggest that perturbed CO2 homeostasis influences the force output characteristics independently of breathing pattern variables.

Involvement of α- and ß-Adrenergic Receptors in Skeletal Muscle Blood Flow Changes During Hyper-/Hypocapnia in Anesthetized Rabbits.

OBJECTIVE: This study investigated the involvement of α1- and ß2-adrenergic receptors in skeletal muscle blood flow changes during variations in ETCO2. METHODS: Forty Japanese White rabbits anesthetized with isoflurane were randomly allocated to 1 of 5 groups: phentolamine, metaproterenol, phenylephrine, butoxamine, and atropine. Heart rate (HR), systolic blood pressure (SBP), common carotid artery blood flow (CCBF), masseter muscle tissue blood flow (MBF), and quadriceps muscle tissue blood flow (QBF) were recorded and analyzed at 3 periods: (1) baseline, (2) during hypercapnia (phentolamine and metaproterenol groups) or hypocapnia (phenylephrine, butoxamine, and atropine groups), and (3) during or after receiving vasoactive agents. RESULTS: MBF and QBF decreased during hypercapnia. The decrease in MBF was smaller than that in QBF. SBP and CCBF increased, while HR decreased. Both MBF and QBF recovered to their baseline levels after phentolamine administration. MBF became greater than its baseline level, while QBF did not fully recover after metaproterenol administration. MBF and QBF increased during hypocapnia. The increase rate in MBF was larger than that in QBF. HR, SBP, and CCBF did not change. Both MBF and QBF decreased to ∼90% to 95% of their baseline levels after phenylephrine or butoxamine administration. Atropine showed no effects on MBF and QBF. CONCLUSION: These results suggest the skeletal muscle blood flow changes observed during hypercapnia and hypocapnia may mainly involve α1-adrenergic but not ß2-adrenergic receptor activity.

Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023.

The respiratory system plays an integral part in maintaining acid-base homeostasis. Normal ventilation participates in the maintenance of an open buffer system, allowing for excretion of CO2 produced from the interaction of nonvolatile acids and bicarbonate. Quantitatively of much greater importance is the excretion of CO2 derived from volatile acids produced from the complete oxidation of fat and carbohydrate. A primary increase in CO2 tension of body fluids is the cause of respiratory acidosis and develops most commonly from one or more of the following: (1) disorders affecting gas exchange across the pulmonary capillary, (2) disorders of the chest wall and the respiratory muscles, and/or (3) inhibition of the medullary respiratory center. Respiratory alkalosis or primary hypocapnia is most commonly caused by disorders that increase alveolar ventilation and is defined by an arterial partial pressure of CO2 <35 mm Hg with subsequent alkalization of body fluids. Both disorders can lead to life-threatening complications, making it of paramount importance for the clinician to have a thorough understanding of the cause and treatment of these acid-base disturbances.

Anticipatory central command on standing decreases cerebral blood velocity causing hypocapnia in hyperpneic postural tachycardia syndrome.

Fifty percent of patients with postural tachycardia syndrome (POTS) are hypocapnic during orthostasis related to initial orthostatic hypotension (iOH). We determined whether iOH drives hypocapnia in POTS by low BP or decreased cerebral blood velocity (CBv). We studied three groups; healthy volunteers (n = 32, 18 ± 3 yr) were compared with POTS, grouped by presence [POTS-low end-tidal CO2 (↓ETCO2), n = 26, 19 ± 2 yr] or absence [POTS-normal upright end-tidal carbon dioxide (nlCO2), n = 28, 19 ± 3 yr] of standing hypocapnia defined by end-tidal CO2 (ETCO2) ≤ 30 mmHg at steady-state, measuring middle cerebral artery CBv, heart rate (HR), and beat-to-beat blood pressure (BP). After 30 min supine, subjects stood for 5 min. Quantities were measured prestanding, at minimum CBv, minimum BP, peak HR, CBv recovery, BP recovery, minimum HR, steady-state, and 5 min. Baroreflex gain was estimated by α index. iOH occurred with similar frequency and minimum BP in POTS-↓ETCO2 and POTS-nlCO2. Minimum CBv was reduced significantly (P < 0.05) in POTS-↓ETCO2 (48 ± 3 cm/s) preceding hypocapnia compared with POTS-nlCO2 (61 ± 3 cm/s) or Control (60 ± 2 cm/s). The anticipatory increased BP was significantly larger (P < 0.05) in POTS (8 ± 1 mmHg vs. 2 ± 1) and began ∼8 s prestanding. HR increased in all subjects, CBv increased significantly (P < 0.05) in both POTS-nlCO2 (76 ± 2 to 85 ± 2 cm/s) and Control (75 ± 2 to 80 ± 2 cm/s) consistent with central command. CBv decreased in POTS-↓ETCO2 (76 ± 3 to 64 ± 3 cm/s) correlating with decreased baroreflex gain. Cerebral conductance [meanCBv/mean arterial blood pressure (MAP)] was reduced in POTS-↓ETCO2 throughout. Data support the hypothesis that excessively reduced CBv during iOH may intermittently reduce carotid body blood flow, sensitizing that organ and producing postural hyperventilation in POTS-↓ETCO2. Excessive fall in CBv occurs in part during prestanding central command and is a facet of defective parasympathetic regulation in POTS.NEW & NOTEWORTHY Dyspnea is frequent in postural tachycardia syndrome (POTS) and is associated with upright hyperpnea and hypocapnia that drives sinus tachycardia. It is initiated by an exaggerated reduction in cerebral conductance and decreased cerebral blood flow (CBF) that precedes the act of standing. This is a form of autonomically mediated "central command." Cerebral blood flow is further reduced by initial orthostatic hypotension common in POTS. Hypocapnia is maintained during the standing response and might account for persistent postural tachycardia.

Hypocapnia is an independent predictor of in-hospital mortality in acute heart failure.

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 (PaCO2 ) 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). PaCO2 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 PaCO2 tertiles and multivariate Cox regression analysis showed that the lowest PaCO2 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.

Lingering Altitude Effects During Piloting and Navigation in a Synthetic Cockpit.

INTRODUCTION: A study was performed to evaluate a cockpit flight simulation suite for measuring moderate altitude effects in a limited subject group. Objectives were to determine whether the apparatus can detect subtle deterioration, record physiological processes throughout hypobaric exposure, and assess recovery.METHODS: Eight subjects trained to perform precision instrument control (PICT) flight and unusual attitude recovery (UAR) and completed chamber flights dedicated to the PICT and UAR, respectively. Each flight comprised five epochs, including ground level pressure (GLP), ascent through altitude plateaus at 10,000, 14,000, and 17,500 ft (3050, 4270, and 5338 m), then postexposure recovery. PICT performance was assessed using control error (FSE) and time-out-of-bounds (TOOB) when pilots exited the flight corridor. UARs were assessed using response times needed to initiate correction and to achieve wings-level attitude. Physiological indices included Spo2, heart rate (HR), end tidal O2 and CO2 pressures, and respiration metrics.RESULTS: Seven subjects completed both flights. PICT performance deteriorated at altitude: FSE increased 33% at 17,513 ft and 21% in Recovery vs. GLP. Mean TOOB increased from 11 s at GLP to 60 s in Recovery. UAR effects were less clear, with some evidence of accelerated responses during and after ascent.CONCLUSIONS: The test paradigm was shown to be effective; piloting impairment was detected during and after exposure. Physiological channels recorded a combination of hypoxia, elevated ventilation, and hypocapnia during ascent, followed by respiratory slowing in recovery. Findings indicate precision piloting and respiration are subject to changes during moderate altitude exposure and may remain altered after Spo2 recovers, and changes may be linked to hypocapnia.Beer J, Morse B, Dart T, Adler S, Sherman P. Lingering altitude effects during piloting and navigation in a synthetic cockpit. Aerosp Med Hum Perform. 2023; 94(3):135-141.

Hypocarbia is associated with adverse outcomes in hypoxic ischaemic encephalopathy (HIE).

AIM: Hypocarbia in the early postnatal period might exacerbate brain injury in babies with hypoxic ischaemic encephalopathy following birth asphyxia. This mini-review summarised studies on pCO2 values that were monitored periodically in term newborns with moderate/severe hypoxic-ischaemic encephalopathy and correlated with short or long-term outcomes. METHODS: We searched the databases MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), web of science and the Cochrane Library and identified nine studies. RESULTS: Among the nine included studies, therapeutic hypothermia was administered in seven studies. In most studies, blood pCO2 levels were measured from birth till 72 h of life or till the endpoint of therapeutic hypothermia. Eight studies showed that any hypocarbia (moderate or severe, or cumulative) was associated with an increased risk of adverse outcomes in the form of brain injury in MRI, death or neurodevelopmental disability. CONCLUSION: Hypocarbia could lead to adverse short-term and long-term outcomes despite therapeutic hypothermia in neonates with HIE. Hence, it is vital to monitor pCO2 levels closely in these infants and consider strategies to maintain pCO2 levels in the normal range.

Hypocapnia attenuates local skin thermal perception to innocuous warm and cool stimuli in normothermic resting humans.

When one is exposed to a stressful situation in their daily life, a common response is hyperventilation. Although the physiological significance of stress-induced hyperventilation remains uncertain, this response may blunt perception of the stress-inducing stimulus. This study examined the effects of voluntary hyperventilation and resultant hypocapnia on the local skin thermal detection threshold in normothermic resting humans. Local skin thermal detection thresholds were measured in 15 young adults (three females) under three breathing conditions: 1) spontaneous breathing (Control trial), 2) voluntary hypocapnic hyperventilation (HH trial), and 3) voluntary normocapnic hyperventilation (NH trial). Local skin thermal detection thresholds were measured using thermostimulators containing a Peltier element that were attached to the forearm and forehead. The temperature of the probe was initially equilibrated to the skin temperature, then gradually increased or decreased at a constant rate (±0.1 °C/s) until the participants felt warmth or coolness. The difference between the initial skin temperature and the local skin temperature at which the participant noticed warmth/coolness was assessed as an index of the local skin warm/cool detection threshold. Local detection of warm and cool stimuli did not differ between the Control and NH trials, but it was blunted in the HH trial as compared with the Control and NH trials, except for detection of warm stimuli on the forearm. These findings suggest that hyperventilation-induced hypocapnia, not hyperventilation per se, attenuates local skin thermal perception, though changes in responses to warm stimuli may not be clearly perceived at some skin areas (e.g., forearm).