Hypercapnic Group Research Articles

Mild hypercapnia versus normocapnia in resuscitated out-of-hospital cardiac arrest patients: a systematic review and meta-analysis

Abstract Introduction After out-of-hospital cardiac arrest (OHCA) resuscitation, current guidelines recommend normocapnia. However, mild hypercapnia may confer several physiological benefits that could enhance post-OHCA outcomes. purpose To assess the effects of moderate hypercapnia versus normocapnia on clinical outcomes after OHCA resuscitation. Methods A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) and observational studies were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through August 15th, 2023. Dichotomous outcomes were pooled using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI). Results We included five studies with a total of 42,076 patients. There was no difference between both groups in all-cause mortality (RR: 1.15, 95% CI [0.89 to 1.49], p=0.29), good neurological recovery (RR: 0.95, 95% CI [0.81 to 1.12], p = 0.56), mechanical ventilation duration (MD: 1.00, 95% CI [-5.41 to7.41], p= 0.76), ICU length of stay (MD: 0.01, 95% CI [-0.28 to 0.30], p= 0.96), neuron-specific enolase level (MD: -20.92, 95% CI [-69.53 to 27.69], p= 0.40), and the incidence of any serious adverse events (RR: 1.55, 95% CI [0.06 to 42.92], p= 0.80). However, length of hospitalization was lower in the mild hypercapnia group (MD: 0.99, 95% CI [-1.85 to -0.14], p= 0.02). Conclusion Mild hypercapnia did not decrease all-cause mortality or improve neurological recovery after OHCA resuscitation compared to normocapnia. However, mild hypercapnia significantly reduced the length of hospital stay.Main outcome

Sonographic evaluation of intracranial hemodynamics and pressure after out-of-hospital cardiac arrest: An exploratory sub-study of the TAME trial

ObjectiveTargeted mild hypercapnia is a potential neuroprotective therapy after cardiac arrest. In this exploratory observational study, we aimed to explore the effects of targeted mild hypercapnia on cerebral microvascular resistance assessed by middle cerebral artery pulsatility index (MCA PI) and intracranial pressure estimated by optic nerve sheath diameter (ONSD) in resuscitated out-of-hospital cardiac arrest (OHCA) patients. Design, setting, participants and interventionsComatose adults resuscitated from OHCA were randomly allocated to targeted mild hypercapnia (PaCO2 50–55 mmHg) or targeted normocapnia (PaCO2 35–45 mmHg) for 24 h in the TAME trial. Main outcome measuresUsing transcranial Doppler and transorbital ultrasound, we obtained MCA PI and ONSD at 4, 24, and 48 h after randomization. Ultrasound parameters were compared between groups using a linear mixed effects model. ResultsTwelve consecutive patients were included, with seven patients in the mild hypercapnia group. MCA PI decreased from 4 to 24 h (p = 0.019) and was lower over the first 24 h in patients allocated to targeted mild hypercapnia compared with targeted normocapnia (p = 0.047). ONSD did not differ between groups or over time. ConclusionCerebral microvascular resistance assessed by MCA PI decreased over 24 h and was lower in OHCA patients treated with targeted mild hypercapnia compared with targeted normocapnia. Targeted mild hypercapnia did not exert substantial effect on intracranial pressure as estimated by ONSD.

Association of Pediatric Postcardiac Arrest Ventilation and Oxygenation with Survival Outcomes.

Rationale: Adult and pediatric studies provide conflicting data regarding whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia, and/or hypocapnia are associated with worse outcomes. Objectives: We sought to determine whether postarrest hypoxemia or postarrest hyperoxemia is associated with lower rates of survival to hospital discharge, compared with postarrest normoxemia, and whether postarrest hypocapnia or hypercapnia is associated with lower rates of survival, compared with postarrest normocapnia. Methods: An embedded prospective observational study during a multicenter interventional cardiopulmonary resuscitation trial was conducted from 2016 to 2021. Patients ⩽18 years old and with a corrected gestational age of ≥37 weeks who received chest compressions for cardiac arrest in one of the 18 intensive care units were included. Exposures during the first 24 hours postarrest were hypoxemia, hyperoxemia, or normoxemia-defined as lowest arterial oxygen tension/pressure (PaO2) <60 mm Hg, highest PaO2 ⩾200 mm Hg, or every PaO2 60-199 mm Hg, respectively-and hypocapnia, hypercapnia, or normocapnia, defined as lowest arterial carbon dioxide tension/pressure (PaCO2) <30 mm Hg, highest PaCO2 ⩾50 mm Hg, or every PaCO2 30-49 mm Hg, respectively. Associations of oxygenation and carbon dioxide group with survival to hospital discharge were assessed using Poisson regression with robust error estimates. Results: The hypoxemia group was less likely to survive to hospital discharge, compared with the normoxemia group (adjusted relative risk [aRR] = 0.71; 95% confidence interval [CI] = 0.58-0.87), whereas survival in the hyperoxemia group did not differ from that in the normoxemia group (aRR = 1.0; 95% CI = 0.87-1.15). The hypercapnia group was less likely to survive to hospital discharge, compared with the normocapnia group (aRR = 0.74; 95% CI = 0.64-0.84), whereas survival in the hypocapnia group did not differ from that in the normocapnia group (aRR = 0.91; 95% CI = 0.74-1.12). Conclusions: Postarrest hypoxemia and hypercapnia were each associated with lower rates of survival to hospital discharge.

Effects of therapeutic hypercapnia on the expression and function of γδT cells in transplanted lungs in rats.

To investigate the effect of therapeutic hypercapnia on the expression and function of gamma delta T (γδ T) cells during ischemia-reperfusion injury (IRI) after lung transplantation. We randomly divided male Wistar rats into three groups (n = 6 in each group), the control group (group N), the IRI group (group I), and the therapeutic hypercapnia group (group H). We then assessed pulmonary edema, neutrophil infiltration, wet-to-dry (W/D) weight ratio, and microscopic histopathology and separately measured the levels of γδT cell surface antigen (TCR) and Interleukin-17 (IL-17) using flow cytometry and enzyme-linked immunosorbent assays (ELISAs). The infiltration of neutrophils and the expression of TCR and IL-17 were significantly increased in the I group compared to the control, and the biopsy edema in group I was more severe. Arterial partial pressure of oxygen (PaO2) was decreased after reperfusion in group I compared with the control group. W/D weight ratio, neutrophil infiltration, and the expression of TCR and IL-17 decreased drastically in the H group compared to the I group. Our findings suggest that γδ T lymphocytes were directly involved in lung injury. In addition, therapeutic hypercapnia effectively reduced the expression of γδ T cells and IL-17, and this has the potential to become a treatment strategy for IRI and an intervention to improve lung function.

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

ObjectivePatients 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. MethodsWe 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. ResultsIntraoperative 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). ConclusionThese 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.

Cardiovascular changes induced by targeted mild hypercapnia after out of hospital cardiac arrest. A sub-study of the TAME cardiac arrest trial

AimHypercapnia may elicit detrimental haemodynamic effects in critically ill patients. We aimed to investigate the consequences of targeted mild hypercapnia versus targeted normocapnia on pulmonary vascular resistance and right ventricular function in patients resuscitated from out-of-hospital cardiac arrest (OHCA). MethodsPre-planned, single-centre, prospective, sub-study of the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial. Patients were randomised to mild hypercapnia (PaCO2 = 6.7–7.3 kPa) or normocapnia (PaCO2 = 4.7–6.0 kPa) for 24 hours. Haemodynamic assessment was performed with right heart catheterisation and serial blood-gas analyses every4th hour for 48 hours. ResultsWe studied 84 patients. Mean pH was 7.24 (95% CI 7.22–7.30) and 7.32 (95% CI 7.31–7.34) with hypercapnia and normocapnia, respectively (P-group < 0.001). Pulmonary vascular resistance index (PVRI), pulmonary artery pulsatility index, and right atrial pressure did not differ between groups (P-group > 0.05). Mean cardiac index was higher with mild hypercapnia (P-group < 0.001): 2.0 (95% CI 1.85–2.1) vs 1.6 (95% CI 1.52–1.76) L/min/m2. Systemic vascular resistance index was 2579 dyne-sec/cm-5/ m2 (95% CI 2356–2830) with hypercapnia, and 3249 dyne-sec/cm-5/ m2 (95% CI 2930–3368) with normocapnia (P-group < 0.001). Stroke volumes (P-group = 0.013) and mixed venous oxygen saturation (P-group < 0.001) were higher in the hypercapnic group. ConclusionIn resuscitated OHCA patients, targeting mild hypercapnia did not increase PVRI or worsen right ventricular function compared to normocapnia. Mild hypercapnia comparatively improved cardiac performance and mixed venous oxygen saturation.

Routine hypercapnic challenge after cervical spinal hemisection affects the size of phrenic motoneurons

After an individual experiences a cervical cord injury, the cell body's adaptation to the smaller size of phrenic motoneurons occurs within several weeks. It is not known whether a routine hypercapnic load can alter this adaptation of phrenic motoneurons. We investigated this question by using rats with high cervical cord hemisection. The rats were divided into four groups: control, hypercapnia, sham, and sham hypercapnia. Within 72 h post-hemisection, the hypercapnia groups began a hypercapnic challenge (20 min/day, 4 times/week for 3 weeks) with 7% CO2 under awake conditions. After the 3-week challenge, the phrenic motoneurons in all of the rats were retrogradely labeled with horseradish peroxidase, and the motoneuron sizes in each group were compared. The average diameter, cross-sectional area, and somal surface area of stained phrenic motoneurons as analyzed by software were significantly smaller in only the control group compared to the other groups. The histogram distribution was unimodal, with larger between-group size differences for motoneurons in the horizontal plane than in the transverse plane. Our findings indicate that a routine hypercapnic challenge may increase the input to phrenic motoneurons and alter the propensity for motoneuron adaptations.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

BackgroundGuidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes.MethodsWe randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale–Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months.ResultsA total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P=0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups.ConclusionsIn patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.)

PaCO2 Levels at Admission Influence the Prognosis of Sepsis Patients: A Nonlinear Relationship

ABSTRACT Background: Sepsis is a life-threatening organ dysfunction caused by a maladjusted host response to infection (Sequential Organ Failure Assessment [SOFA] ≥ 2). PaCO2 is a blood gas that is commonly tested in hospitalized patients. Few studies have investigated how abnormal PaCO2 levels influence the prognosis of sepsis patients. Methods: A retrospective study was applied to data on sepsis patients extracted from the MIMIC-III public database and the results of their first PaCO2 examination after admission. The outcome measure was all-cause death within 90 days of follow-up. The patients were divided into five quintile groups, and the relationship between PaCO2 and all-cause death in sepsis patients was studied using restricted cubic splines (RCSs). Results: Our study included 4898 sepsis patients, the hypocapnia (PaCO2 &lt; 31 mmHg) and hypercapnia (PaCO2 ≥ 49 mmHg) groups were associated with the risk of death in sepsis patients using quintile grouping and the multivariate Cox model, with HRs of 1.12 (95% CI = 1.03–1.29) and 1.25 (95% CI = 1.10–1.41), respectively, when compared with the control group (37 ≤ PaCO2 &lt; 41 mmHg). The relationship between PaCO2 and all-cause death in sepsis patients was U-shaped. Conclusion: The presence of hypercapnia and hypocapnia at the time of hospital admission will have adverse effects on all-cause death in sepsis patients.

A retrospective study of the role of hypercapnia in patients with acromegaly

BackgroundAcromegaly is a multisystemic disease characterized by an excessive release of growth hormone (GH) and insulin-like growth factor-1. Obstructive sleep apnea (OSA) is a common consequence of acromegaly, and hypercapnia is frequently observed in patients with acromegaly, OSA, and obesity. However, the effects of hypercapnia on acromegaly remain unknown. This study was designed to investigate whether there are differences in clinical symptoms, sleep variables, and biochemical remission after surgery for acromegaly in patients with OSA with or without hypercapnia.MethodsA retrospective analysis was conducted involving patients with acromegaly and OSA. The pharmacotherapy history for acromegaly before surgery, anthropometric measures, blood gas, sleep monitoring data, and biochemical assays of hypercapnic and eucapnic individuals were collected 1–2 weeks before surgery. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for failed postoperative biochemical remission.ResultsIn this study, 94 patients with OSA and acromegaly were included. Among them, 25 (26.6%) had hypercapnia. The hypercapnic group had higher body mass index (92% vs. 62.3%; p = 0.005) and poorer nocturnal hypoxemia index. No serological differences were found between the two groups. According to the post-surgery GH level, 52 patients (55.3%) reached biochemical remission. Univariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.02–6.55), instead of hypercapnia (OR, 0.61; 95% CI, 0.24–1.58), was associated with lower remission rates. Patients who received pharmacotherapy for acromegaly before surgery (OR, 0.21; 95% CI, 0.06–0.79) and had higher thyroid-stimulating hormone levels (OR, 0.53; 95% CI, 0.32–0.88) were more likely to have biochemical remission after surgery. Multivariate analysis further showed that only diabetes mellitus (OR, 3.29; 95% CI, 1.15–9.46) and preoperative pharmacotherapy (OR, 0.21; 95% CI, 0.06–0.83) remained significant. Hypercapnia, hormone levels, and sleep indicators had no effect on biochemical remission after surgery.ConclusionsSingle-center evidence shows that hypercapnia alone may not be a risk factor for lower biochemical remission rates. Correcting hypercapnia does not appear to be required before surgery. More evidence is needed to further support this conclusion.

Thiol/Disulfide Homeostasis and Ischemia-Modified Albumin Levels in 61 Patients with Hypercapnia: A Case-Control Study.

BACKGROUND Hypercapnia is abnormally high arterial partial pressure of carbon dioxide (CO₂). CO₂ can affect redox signaling mechanisms, leading to production of oxidative derivatives. Thiol is formed by attaching a sulfhydryl group to a carbon atom. Under oxidative stress, it forms covalent bonds called thiol disulphide bonds. Serum albumin is modified to ischemia-modified albumin (IMA) by exposure to free radicals. This case-control study aimed to evaluate thiol/disulphide homeostasis and IMA levels in 61 patients with hypercapnia. MATERIAL AND METHODS We studied 61 patients with hypercapnia and 61 normocapnic volunteers in the control group, between May 2018 and January 2019; 56 of these patients were diagnosed with chronic obstructive pulmonary disease and 5 of them were diagnosed with obstructive sleep apnea syndrome. Arterial blood samples analyzed by using the Ellman reagent for thiol/disulphide data. A colorometric assay was used for detection of IMA levels. RESULTS Native thiol and total thiol values in the hypercapnic group were significantly lower than in the control group (P=0.024, P=0.006 respectively), as IMA values were significantly higher (P<0.001). There was no statistically significant difference between the hypercapnic and control groups in terms of disulphide, disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol values (P>0.05). CONCLUSIONS In hypercapnic patients, there are changes in thiol/disulphide homeostasis and IMA levels. All significant differences in this study support that changes in thiol disulphide homeostasis and IMA in hypercapnic patients are indicators of oxidative stress.

Daytime Hypercapnia Impairs Working Memory in Young and Middle-Aged Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Obstructive sleep apnea hypopnea syndrome (OSAHS) can lead to cognitive impairment, though few studies have so far examined hypercapnia as its causal mechanism, due to the invasive nature of conventional arterial CO2 measurement. The study aims to investigate the effects of daytime hypercapnia on working memory in young and middle-aged patients with OSAHS. This prospective study screened 218 patients and eventually recruited 131 patients (aged 25-60 years) with polysomnography (PSG)-diagnosed OSAHS. Using a cut-off of 45mmHg daytime transcutaneous partial pressure of carbon dioxide (PtcCO2), 86 patients were assigned into the normocapnic group and 45 patients into the hypercapnic group. Working memory was evaluated using the Digit Span Backward Test (DSB) and the Cambridge Neuropsychological Test Automated Battery. Compared with the normocapnic group, the hypercapnic group performed worse in verbal, visual, and spatial working memory tasks. PtcCO2≥45mmHg was an independent predictor for lower DSB scores (OR=4.057), lower accuracy in the immediate Pattern Recognition Memory (OR=2.600), delayed Pattern Recognition Memory (OR=2.766) and Spatial Recognition Memory (OR=2.722) tasks, lower Spatial Span scores (OR=4.795), and more between errors in the Spatial Working Memory task (OR=2.734 and 2.558, respectively). Notably, PSG indicators of hypoxia and sleep fragmentation did not predict task performance. Hypercapnia may be plays an important role in working memory impairment in patients with OSAHS, perhaps more so than hypoxia and sleep fragmentation. Routine CO2 monitoring in these patients could prove of utility in clinical practices.

Beneficial Impact of Hypercapnic Conditions During Early Incubation on Broiler Hatchability. Embryo Mortality and Postnatal Performance

We assessed the extent to which CO2 levels altered different hatching and chick parameters. In Experiments 1 and 2, a total of 16,184 eggs from Cobb 500 breeders were incubated in single stage incubators under three different conditions: (a) standard ventilated incubator (CON, Exp.1 and 2); (b) increasing CO2 levels during the first 10 days of incubation until 0.7% (V7000, Exp. 1) and (c) until 0.8% (V8000, Exp. 2). High levels of CO2 improved hatchability, possibly due to lower embryo mortality from ED18 to ED21. Internal and external pipping in experiment V8000 started later than in CON; nevertheless, the hatch still occurred before in V8000 as a result of the shorter durations of external pipping and hatch. In Experiment 3, a total of 12,138 eggs from Cobb 500 were incubated in single stage incubators under three different conditions: (a) standard ventilated incubator (CON); (b) increasing CO2 levels until 1.0% with ventilation (V10000); and (c) increasing CO2 levels until 1.0% without ventilation (NV10000). Hypercapnic conditions led to better hatchability and lower embryo mortality from ED18 to ED21. Internal pipping started earlier in NV10000, but only V10000 differed from CON in terms of the average time for hatch. Hypercapnic groups also showed shorter durations of external pipping and hatch when compared to CON. Post-hatch analysis revealed no differences among incubation conditions in terms of body weight gain, feed conversion ratio, mortality by sudden death syndrome, and production factor. Nevertheless, V10000 showed a lower mortality by ascites and a better viability when compared to CON, while NV10000 presented a higher mortality by other causes. Altogether, our findings indicate that in addition to not being detrimental to embryo survival, high CO2 levels reduce embryonic mortality at 18-21 days of incubation and increase hatchability.

DIFFERENCES IN OUTCOMES OF COPD EXACERBATIONS WITH DEGREE OF HYPERCAPNIA: AN OBSERVATIONAL PERSPECTIVE

DIFFERENCES IN OUTCOMES OF COPD EXACERBATIONS WITH DEGREE OF HYPERCAPNIA: AN OBSERVATIONAL PERSPECTIVE

Is hypocapnia a risk factor for non-invasive ventilation failure in cardiogenic acute pulmonary edema?

The impact of hypocapnia in the prognosis of cardiogenic acute pulmonary edema (CAPE) has not been sufficiently studied. The aim of this study was to analyse whether hypocapnia is a risk factor for non-invasive ventilation (NIV) failure and hospital mortality, in CAPE patients CAPE. Retrospective observational study of all patients with CAPE treated with NIV. Patients were classified in three groups according to PaCO2 level (hypocapnic, eucapnic and hypercapnic). NIV failure was defined as the need for endotracheal intubation and/or death. 1138 patients were analysed, 390 (34.3%) of which had hypocapnia, 186 (16.3%) had normocapnia and 562 (49.4%) had hypercapnia. NIV failure was more frequent in hypocapnic (60 patients, 15.4%) than in eucapnic (16 pacientes, 8.6%) and hypercapnic group (562 pacientes, 10.7%), with statistical significance (p = 0.027), as well as hospital mortality, 73 (18.7%), 19(10.2%) and 83 (14.8%) respectively (p = 0.026). The predicted factors for NIV failure were the presence of do-not-intubate order, complications related to NIV, a lower left ventricular ejection fraction, higher SAPS II and SOFA score and a higher HACOR score at one hour of NIV initiation. Hypocapnia in patients with CAPE is associated with NIV failure and a greater in-hospital mortality.

Intermittent Exposure of Hypercapnia Suppresses Allograft Rejection via Induction of Treg Differentiation and Inhibition of Neutrophil Accumulation.

Background: In the management of major burn wounds, allogeneic skin transplantation is a critical procedure to improve wound repair. Our previous works found that intermittent exposure to carbon dioxide leads to permissive hypercapnia (HCA) and prolongs skin allograft survival. However, the modulatory effects of HCA exposure on the immune system are not well understood. Objectives: Our purpose was to investigate how intermittent exposure to HCA can effectively reduce the immune reaction to allogeneic skin graft rejection. Methods: A fully major histocompatibility complex-incompatible skin transplant from BALB/c to C57BL/6 mice model was utilized. Immune cells from splenic and draining lymph nodes were analyzed by flow cytometry. Serum proinflammatory cytokines were analyzed by ELISA. Results: Serum levels of IFN-γ, IL-2, IL-6, and TNF-α were significantly decreased in the HCA group. Additionally, the percentage of CD8+ cells in draining lymph nodes was significantly lower in HCA than in the control group. Moreover, the generation rate of FoxP3+ regulatory T cells (Tregs) from spleen naïve CD4+ T cells was increased by intermittent exposure to carbon dioxide. The infiltrated neutrophils were also eliminated by HCA. Taken together, we concluded that intermittent hypercapnia exposure could effectively suppress skin rejection by stimulating Treg cell generation and suppressing immune reactions.

The effects of high-flow nasal cannula oxygen therapy in dyspnea patients with and without hypercapnia in the emergency department: a retrospective, propensity score-matched cohort study

We aimed to study the difference in treatment outcomes and prognoses in patients with or without hypercapnia who visited the emergency department for dyspnea and received high-flow nasal cannula (HFNC) therapy. This was a retrospective observational study. Patients who received HFNC therapy were divided into hypercapnic and non-hypercapnic. The intubation rates were compared for the primary outcome. For the secondary outcomes, intensive care unit (ICU) admission, length of hospital stay, length of ICU stay, and mortality were compared. Moreover, changes in arterial blood gas results were reported in terms of group, time, and group-by-time interaction. A total of 517 patients were enrolled, of whom 126 were included in the hypercapnic group. After propensity score matching, 94 patients were selected. The intubation rate was not significantly different between the two groups (p = 0.23). No differences were found in ICU admission, length of hospital stay, length of ICU stay, and mortality. The changes in arterial blood gas results pre- and post-HFNC therapy showed a difference in the group-by-time interaction for partial pressure of carbon dioxide (p = 0.038). We found that there was no difference in treatment outcomes and prognoses in patients with or without hypercapnia who visited the emergency department for dyspnea and received HFNC therapy.

Comparison of the Effects of Normocapnia and Mild Hypercapnia on the Optic Nerve Sheath Diameter and Regional Cerebral Oxygen Saturation in Patients Undergoing Gynecological Laparoscopy with Total Intravenous Anesthesia.

Cerebral hemodynamics may be altered by hypercapnia during a lung-protective ventilation (LPV), CO2 pneumoperitoneum, and Trendelenburg position during general anesthesia. The purpose of this study was to compare the effects of normocapnia and mild hypercapnia on the optic nerve sheath diameter (ONSD), regional cerebral oxygen saturation (rSO2), and intraoperative respiratory mechanics in patients undergoing gynecological laparoscopy under total intravenous anesthesia (TIVA). Sixty patients (aged between 19 and 65 years) scheduled for laparoscopic gynecological surgery in the Trendelenburg position. Patients under propofol/remifentanil total intravenous anesthesia were randomly assigned to either the normocapnia group (target PaCO2 = 35 mmHg, n = 30) or the hypercapnia group (target PaCO2 = 50 mmHg, n = 30). The ONSD, rSO2, and respiratory and hemodynamic parameters were measured at 5 min after anesthetic induction (Tind) in the supine position, and at 10 min and 40 min after pneumoperitoneum (Tpp10 and Tpp40, respectively) in the Trendelenburg position. There was no significant intergroup difference in change over time in the ONSD (p = 0.318). The ONSD increased significantly at Tpp40 when compared to Tind in both normocapnia and hypercapnia groups (p = 0.02 and 0.002, respectively). There was a significant intergroup difference in changes over time in the rSO2 (p < 0.001). The rSO2 decreased significantly in the normocapnia group (p = 0.01), whereas it increased significantly in the hypercapnia group at Tpp40 compared with Tind (p = 0.002). Alveolar dead space was significantly higher in the normocapnia group than in the hypercapnia group at Tpp40 (p = 0.001). In conclusion, mild hypercapnia during the LPV might not aggravate the increase in the ONSD during CO2 pneumoperitoneum in the Trendelenburg position and could improve rSO2 compared to normocapnia in patients undergoing gynecological laparoscopy with TIVA.

Effects of daytime hypercapnia on logical memory and working memory in patients with obstructive sleep apnea hypopnea syndrome

Objective: To investigate the effects of daytime hypercapnia on logical memory and working memory in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: This prospective study recruited patients complaining of snoring and diagnosed with OSAHS at the Sleep Center of the Second Affiliated Hospital of Soochow University from January to November 2020. Patients were assessed clinically and scored for their memory function. All patients underwent daytime transcutaneous carbon dioxide (PtcCO2) test, and overnight polysomnography (PSG). Logical memory was scored using the Logical Memory Test (LMT), while working memory was evaluated by Digit Span Test (DST) and Cambridge Neuropsychological Test Automated Battery (CANTAB) which included Pattern Recognition Memory (PRM), Spatial Span (SSP), and Spatial Working Memory (SWM). Patients were divided into the normocapnic group and the hypercapnic group using the daytime PtcCO2 test. The clinical and PSG parameters and the memory test scores between the two groups were compared. Binary logistic stepwise regression was conducted to identify risk factors of memory impairment in OSAHS patients. Results: Among the 123 enrolled OSAHS patients, 79 were normocapnic and 44 were hypercapnic. There was no significant difference in the general clinical parameters between the two groups. The snoring history in years in the hypercapnic group was longer than that in the normocapnic group (P<0.05). Compared with the normocapnic group, the apnea-hyponea index (AHI), oxygen desaturation index (ODI) and percentage of total sleep time with oxygen saturation level<90% (TS90) of the hypercapnic group were higher (all P<0.05), while other PSG parameters exhibited no statistically significant differences. There was no statistically significant difference in the immediate logical memory and PRM immediate accuracy rate between the two groups, while the delayed logical memory, verbal and spatial working memory, and executive function were worse in the hypercapnic group, as shown by lower total LMT scores, lower DST, lower SSP scores (all P<0.05), and higher between errors and strategy scores (P<0.01) of SWM in the hypercapnic group. Binary logistic stepwise regression showed that PtcCO2 ≥45 mmHg (1 mmHg=0.133 kPa, OR=3.055, 95%CI 1.359-6.868, P=0.007) and higher body mass index (BMI) (OR=1.132, 95%CI 1.005-1.275, P=0.041) were risk factors for poor performance in Digit Span Backwards Test. Therefore, PtcCO2 ≥45 mmHg was an independent risk factors for poor performance in delayed LMT, SSP, and between errors and strategy scores in SWM (OR=3.109, 3.941, 3.238 and 2.785, respectively, all P<0.05). Conclusion: Hypercapnia had negative impacts on logical memory and working memory of OSAHS patients, especially on the delayed logical memory, verbal working memory and spatial working memory impairment.

Hypercapnia versus normocapnia for emergence from desflurane anaesthesia

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