PaCO2 is nonlinearly associated with NIV failure in patients with hypoxemic respiratory failure.

OBJECTIVE: To explore the association between PaCO2 and noninvasive ventilation (NIV) failure in patients with hypoxemic respiratory failure. METHODS: A retrospective study was performed in a respiratory ICU of a teaching hospital. Patients admitted to ICU between 2011 and 2019 were screened. We enrolled the patients with hypoxemic respiratory failure. However, patients who used NIV due to acute-on-chronic respiratory failure or heart failure were excluded. Data before the use of NIV were collected. Requirement of intubation was defined as NIV failure. RESULTS: A total of 1029 patients were enrolled in final analysis. The rate of NIV failure was 45% (461/1029). A nonlinear relationship between PaCO2 and NIV failure was found by restricted cubic splines (p = 0.03). The inflection point was 32 mmHg. The rate of NIV failure was 42% (224/535) in patients with PaCO2 >32 mmHg. However, it increased to 48% (237/494) in those with PaCO2 ≤ 32 mmHg. The crude and adjusted hazard ratio (HR) for NIV failure was 1.36 (95%CI:1.13-1.64) and 1.23(1.01-1.49), respectively, if the patients with PaCO2 >32 mmHg were set as reference. In patients with PaCO2 ≤ 32 mmHg, one unit increment of PaCO2 was associated with 5% reduction of NIV failure. However, it did not associate with NIV failure in patients with PaCO2 >32 mmHg. CONCLUSIONS: PaCO2 and NIV failure was nonlinear relationship. The inflection point was 32 mmHg. Below the inflection point, lower PaCO2 was associated with higher NIV failure. However, it did not associate with NIV failure above this point.

Prognostic value of arterial carbon dioxide tension during cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients receiving extracorporeal resuscitation.

BACKGROUND: Current guidelines on extracorporeal cardiopulmonary resuscitation (ECPR) recommend careful patient selection, but precise criteria are lacking. Arterial carbon dioxide tension (PaCO2) has prognostic value in out-of-hospital cardiac arrest (OHCA) patients but has been less studied in patients receiving ECPR. We studied the relationship between PaCO2 during cardiopulmonary resuscitation (CPR) and neurological outcomes of OHCA patients receiving ECPR and tested whether PaCO2 could help ECPR selection. METHODS: This single-centre retrospective study enrolled 152 OHCA patients who received ECPR between January 2012 and December 2020. Favorable neurological outcome (FO) at discharge was the primary outcome. We used multivariable logistic regression to determine the independent variables for FO and generalised additive model (GAM) to determine the relationship between PaCO2 and FO. Subgroup analyses were performed to test discriminative ability of PaCO2 in subgroups of OHCA patients. RESULTS: Multivariable logistic regression showed that PaCO2 was independently associated with FO after adjusting for other favorable resuscitation characteristics (Odds ratio [OR] 0.23, 95% Confidence Interval [CI] 0.08-0.66, p-value = 0.006). GAM showed a near-linear reverse relationship between PaCO2 and FO. PaCO2 < 70 mmHg was the cutoff point for predicting FO. PaCO2 also had prognostic value in patients with less favorable characteristics, including non-shockable rhythm (OR, 3.78) or low flow time > 60 min (OR, 4.66). CONCLUSION: PaCO2 before ECMO implementation had prognostic value for neurological outcomes in OHCA patients. Patients with PaCO2 < 70 mmHg had higher possibility of FO, even in those with non-shockable rhythm or longer low-flow duration. PaCO2 could serve as an ECPR selection criterion.

The level of partial pressure of carbon dioxide affects respiratory effort in COVID-19 patients undergoing pressure support ventilation with extracorporeal membrane oxygenation.

BACKGROUND: Patients with COVID-19 undergoing pressure support ventilation (PSV) with extracorporeal membrane oxygenation (ECMO) commonly had high respiratory drive, which could cause self-inflicted lung injury. The aim of this study was to evaluate the influence of different levels of partial pressure of carbon dioxide(PaCO2) on respiratory effort in COVID-19 patients undergoing PSV with ECMO. METHODS: ECMO gas flow was downregulated from baseline (respiratory rate < 25 bpm, peak airway pressure < 25 cm H2O, tidal volume < 6 mL/kg, PaCO2 < 40 mmHg) until PaCO2 increased by 5 - 10 mmHg. The pressure muscle index (PMI) and airway pressure swing during occlusion (ΔPOCC) were used to monitor respiratory effort, and they were measured before and after enforcement of the regulations. RESULTS: Ten patients with COVID-19 who had undergone ECMO were enrolled in this prospective study. When the PaCO2 increased from 36 (36 - 37) to 42 (41-43) mmHg (p = 0.0020), there was a significant increase in ΔPOCC [from 5.6 (4.7-8.0) to 11.1 (8.5-13.1) cm H2O, p = 0.0020] and PMI [from 3.0 ± 1.4 to 6.5 ± 2.1 cm H2O, p < 0.0001]. Meanwhile, increased inspiratory effort determined by elevated PaCO2 levels led to enhancement of tidal volume from 4.1 ± 1.2 mL/kg to 5.3 ± 1.5 mL/kg (p = 0.0003) and respiratory rate from 13 ± 2 to 15 ± 2 bpm (p = 0.0266). In addition, the increase in PaCO2 was linearly correlated with changes in ΔPOCC and PMI (R2 = 0.7293, p = 0.0003 and R2 = 0.4105, p = 0.0460, respectively). CONCLUSIONS: In patients with COVID-19 undergoing PSV with ECMO, an increase of PaCO2 could increase the inspiratory effort.

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.

Differences in time-frequency characteristics between healthy controls and TBI patients during hypercapnia assessed via fNIRS.

Damage to the cerebrovascular network is a universal feature of traumatic brain injury (TBI). This damage is present during different phases of the injury and can be non-invasively assessed using functional near infrared spectroscopy (fNIRS). fNIRS signals are influenced by partial arterial carbon dioxide (PaCO2), neurogenic, Mayer waves, respiratory and cardiac oscillations, whose characteristics vary in time and frequency and may differ in the presence of TBI. Therefore, this study aims to investigate differences in time-frequency characteristics of these fNIRS signal components between healthy controls and TBI patients and characterize the changes in their characteristics across phases of the injury. Data from 11 healthy controls and 21 TBI patients were collected during the hypercapnic protocol. Results demonstrated significant differences in low-frequency oscillations between healthy controls and TBI patients, with the largest differences observed in Mayer wave band (0.06 to 0.15 Hz), followed by the PaCO2 band (0.012 to 0.02 Hz). The effects within these bands were opposite, with (i) Mayer wave activity being lower in TBI patients during acute phase of the injury (d = 0.37 [0.16, 0.57]) and decreasing further during subacute (d = 0.66 [0.44, 0.87]) and postacute (d = 0.75 [0.50, 0.99]) phases; (ii) PaCO2 activity being lower in TBI patients only during acute phase of the injury (d = 0.36 [0.15, 0.56]) and stabilizing to healthy levels by the subacute phase. These findings demonstrate that TBI patients have impairments in low frequency oscillations related to different mechanisms and that these impairments evolve differently over the course of injury.

Clinical usefulness of end-tidal CO2 measured using a portable capnometer in patients with respiratory disease.

INTRODUCTION: This study aimed to evaluate the correlation and agreement between end-tidal CO2 (EtCO2 ) measured with the novel portable capnometer (CapnoEye®) and partial pressure of arterial carbon dioxide (PaCO2 ) levels in patients with respiratory diseases and to compare the efficacy of EtCO2 and PvCO2 in predicting PaCO2 levels. METHODS: We analyzed the correlation and the agreement between EtCO2 and PaCO2 and between PvCO2 and PaCO2 using Pearson's moment correlation coefficient in patients with type 1 and type 2 respiratory failure and both groups overall. RESULTS: A total of 100 samples were included that comprised 67 men (67%). The mean age of the subjects was 77 ± 13 years. Chronic obstructive pulmonary disease (COPD) (43%) was the most common disease. There was a high correlation between EtCO2 and PaCO2 (r = 0.88; p < 0.0001). Sixty-six PvCO2 samples were obtained, and there was a high correlation between PvCO2 and PaCO2 (r = 0.81; p < 0.0001). Regarding type 2 respiratory failure, there was a high correlation between EtCO2 and PaCO2 (r = 0.81). The Bland-Altman analysis between PaCO2 and EtCO2 revealed a bias of 5.7 mmHg, with limits of agreement ranging from -5.1 mmHg to 16.5 mmHg. In contrast, the analysis between PaCO2 and PvCO2 revealed a bias of -6.8 mmHg, and the limits of agreement ranged from -22.13 mmHg to 8.53 mmHg. CONCLUSION: EtCO2 measured by CapnoEye® was significantly correlated to PaCO2 levels in patients with respiratory diseases. Moreover, CapnoEye® may be more useful for predicting hypercapnia conditions in which respiratory diseases are compared with measure PvCO2 .

Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report.

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as 'probable' on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.

Systematic review and meta-analysis: value of venous blood gas in the diagnosis of acute exacerbation of chronic obstructive pulmonary disease in Emergency Department.

BACKGROUND: at present, arterial blood gas (ABG) analysis is widely used in the diagnosis and treatment evaluation of acute exacerbation of chronic obstructive pulmonary disease (COPD) in emergency department, but it has the risk of thrombosis and bleeding. In recent years, venous blood gas (VBG) analysis has become more and more popular, but its clinical diagnostic value in emergency patients with acute exacerbation of COPD remains unclear. METHODS: relevant clinical studies on the diagnosis of acute exacerbation of COPD by blood gas analysis were searched in Medline, Excerpta Medica Database (EMBASE), Elton B. Stephens. Company (EBSCO), OVID, China Biomedical Database, and Wanfang Database from the establishment of the database to January 2010 to September 2021, Meta-analysis was performed on the data with RevMan5.3. The differences of blood gas analysis indicators potential of hydrogen (pH), partial pressure of carbon dioxide (PaCO2), and hydro-carbonate (HCO3) were compared between the arterial blood gas group and the venous blood gas group. Heterogeneity of results was assessed with Chi2 test and I2 in RevMan5.3. RESULTS: a total of 7 articles with 1,257 subjects were included in this study. Newcastle-Ottawa scale (NOS) scores were higher than six points. In relation to the ABG analysis and VBG analysis, there was no significant difference in the potential of hydrogen (pH) [mean difference (MD) =-0.00, 95% confidence interval (CI) =0.05-0.04, Z=0.19, P=0.85]; however, there were significant differences in the partial pressure of carbon dioxide (PaCO2) (MD =5.32, 95% CI =3.32-7.33, Z=5.20, P<0.00001) and hydro-carbonate (HCO3) (MD =1.05, 95% CI =0.27-1.83, Z=2.63, P=0.009). CONCLUSIONS: there were differences between ABG and VBG in the diagnosis of patients with acute exacerbation of COPD in the emergency department. Due to the small number of included literatures, further verification is needed.

End-Tidal to Arterial Pco2 Ratio as Guide to Weaning from Venovenous Extracorporeal Membrane Oxygenation.

Rationale: Weaning from venovenous extracorporeal membrane oxygenation (VV-ECMO) is based on oxygenation and not on carbon dioxide elimination. Objectives: To predict readiness to wean from VV-ECMO. Methods: In this multicenter study of mechanically ventilated adults with severe acute respiratory distress syndrome receiving VV-ECMO, we investigated a variable based on CO2 elimination. The study included a prospective interventional study of a physiological cohort (n = 26) and a retrospective clinical cohort (n = 638). Measurements and Main Results: Weaning failure in the clinical and physiological cohorts were 37% and 42%, respectively. The main cause of failure in the physiological cohort was high inspiratory effort or respiratory rate. All patients exhaled similar amounts of CO2, but in patients who failed the weaning trial, [Formula: see text]e was higher to maintain the PaCO2 unchanged. The effort to eliminate one unit-volume of CO2, was double in patients who failed (68.9 [42.4-123] vs. 39 [20.1-57] cm H2O/[L/min]; P = 0.007), owing to the higher physiological Vd (68 [58.73] % vs. 54 [41.64] %; P = 0.012). End-tidal partial carbon dioxide pressure (PetCO2)/PaCO2 ratio was a clinical variable strongly associated with weaning outcome at baseline, with area under the receiver operating characteristic curve of 0.87 (95% confidence interval [CI], 0.71-1). Similarly, the PetCO2/PaCO2 ratio was associated with weaning outcome in the clinical cohort both before the weaning trial (odds ratio, 4.14; 95% CI, 1.32-12.2; P = 0.015) and at a sweep gas flow of zero (odds ratio, 13.1; 95% CI, 4-44.4; P < 0.001). Conclusions: The primary reason for weaning failure from VV-ECMO is high effort to eliminate CO2. A higher PetCO2/PaCO2 ratio was associated with greater likelihood of weaning from VV-ECMO.

Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD.

OBJECTIVE: To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). METHODS: Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. RESULTS: (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. CONCLUSION: Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.

Optimal Targets of the First 24-h Partial Pressure of Carbon Dioxide in Patients with Cerebral Injury: Data from the MIMIC-III and IV Database.

BACKGROUND: It is generally believed that hypercapnia and hypocapnia will cause secondary injury to patients with craniocerebral diseases, but a small number of studies have shown that they may have potential benefits. We assessed the impact of partial pressure of arterial carbon dioxide (PaCO2) on in-hospital mortality of patients with craniocerebral diseases. The hypothesis of this research was that there is a nonlinear correlation between PaCO2 and in-hospital mortality in patients with craniocerebral diseases and that mortality rate is the lowest when PaCO2 is in a normal range. METHODS: We identified patients with craniocerebral diseases from Medical Information Mart for Intensive Care third and fourth edition databases. Cox regression analysis and restricted cubic splines were used to examine the association between PaCO2 and in-hospital mortality. RESULTS: Nine thousand six hundred and sixty patients were identified. A U-shaped association was found between the first 24-h PaCO2 and in-hospital mortality in all participants. The nadir for in-hospital mortality risk was estimated to be at 39.5 mm Hg (p for nonlinearity < 0.001). In the subsequent subgroup analysis, similar results were found in patients with traumatic brain injury, metabolic or toxic encephalopathy, subarachnoid hemorrhage, cerebral infarction, and other encephalopathies. Besides, the mortality risk reached a nadir at PaCO2 in the range of 35-45 mm Hg. The restricted cubic splines showed a U-shaped association between the first 24-h PaCO2 and in-hospital mortality in patients with other intracerebral hemorrhage and cerebral tumor. Nonetheless, nonlinearity tests were not statistically significant. In addition, Cox regression analysis showed that PaCO2 ranging 35-45 mm Hg had the lowest death risk in most patients. For patients with hypoxic-ischemic encephalopathy and intracranial infections, the first 24-h PaCO2 and in-hospital mortality did not seem to be correlated. CONCLUSIONS: Both hypercapnia and hypocapnia are harmful to most patients with craniocerebral diseases. Keeping the first 24-h PaCO2 in the normal range (35-45 mm Hg) is associated with lower death risk.

Validation of transcutaneous carbon dioxide monitoring using an artificial lung during adult pulsatile cardiopulmonary bypass.

Measurements of transcutaneous carbon dioxide (tcCO2) have been used in multiple venues, such as during procedures utilizing jet ventilation, hyperbaric oxygen therapy, as well as both the adult and neo-natal ICUs. However, tcCO2 measurements have not been validated under conditions which utilize an artificial lung, such cardiopulmonary bypass (CPB). The purpose of this study was to (1) validate the use of tcCO2 using an artificial lung during CPB and (2) identify a location for the sensor that would optimize estimation of PaCO2 when compared to the gold standard of blood gas analysis.tcCO2 measurements (N = 185) were collected every 30 min during 54 pulsatile CPB procedures. The agreement/differences between the tcCO2 and the PaCO2 were compared by three sensor locations. Compared to the earlobe or the forehead, the submandibular PtcCO2 values agreed best with the PaCO2 and with a median difference of -.03 mmHg (IQR = 5.4, p < 0.001). The small median difference and acceptable IQR support the validity of the tcCO2 measurement. The multiple linear regression model for predicting the agreement between the submandibular tcCO2 and PaCO2 included the SvO2, the oxygenator gas to blood flow ratio, and the native perfusion index (R2 = 0.699, df = 1, 60; F = 19.1, p < 0.001).Our experience in utilizing tcCO2 during CPB has demonstrated accuracy in estimating PaCO2 when compared to the gold standard arterial blood gas analysis, even during CO2 flooding of the surgical field.

Lung Function and Symptoms in Post-COVID-19 Patients: A Single-Center Experience.

OBJECTIVE: To address the lack of information about clinical sequelae of coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: Previously hospitalized COVID-19 patients who were attending the outpatient clinic for post-COVID-19 patients (ASST Ovest Milanese, Magenta, Italy) were included in this retrospective study. They underwent blood draw for complete blood count, C-reactive protein, ferritin, D-dimer, and arterial blood gas analysis and chest high-resolution computed tomography (HRCT) scan. The primary endpoint was the assessment of blood gas exchanges after 3 months. Other endpoints included the assessment of symptoms and chest HRCT scan abnormalities and changes in inflammatory biomarkers after 3 months from hospital admission. RESULTS: Eighty-eight patients (n = 65 men; 73.9%) were included. Admission arterial blood gas analysis showed hypoxia and hypocapnia and an arterial partial pressure of oxygen/fractional inspired oxygen ratio of 271.4 (interquartile range [IQR]: 238-304.7) mm Hg that greatly improved after 3 months (426.19 [IQR: 395.2-461.9] mm Hg, P<.001). Forty percent of patients were still hypocapnic after 3 months. Inflammatory biomarkers dramatically improved after 3 months from hospitalization. Fever, resting dyspnea, and cough were common at hospital admission and improved after 3 months, when dyspnea on exertion and arthralgias arose. On chest HRCT scan, more than half of individuals still presented with interstitial involvement after 3 months. Positive correlations between the interstitial pattern at 3 months and dyspnea on admission were found. C-reactive protein at admission was positively associated with the presence of interstitial involvement at follow-up. The persistence of cough was associated with presence of bronchiectasis and consolidation on follow-up chest HRCT scan. CONCLUSION: Whereas inflammatory biomarker levels normalized after 3 months, signs of lung damage persisted for a longer period. These findings support the need for implementing post-COVID-19 outpatient clinics to closely follow-up COVID-19 patients after hospitalization.

Artificial intelligence in clinical care amidst COVID-19 pandemic: A systematic review.

The worldwide health crisis caused by the SARS-Cov-2 virus has resulted in>3 million deaths so far. Improving early screening, diagnosis and prognosis of the disease are critical steps in assisting healthcare professionals to save lives during this pandemic. Since WHO declared the COVID-19 outbreak as a pandemic, several studies have been conducted using Artificial Intelligence techniques to optimize these steps on clinical settings in terms of quality, accuracy and most importantly time. The objective of this study is to conduct a systematic literature review on published and preprint reports of Artificial Intelligence models developed and validated for screening, diagnosis and prognosis of the coronavirus disease 2019. We included 101 studies, published from January 1st, 2020 to December 30th, 2020, that developed AI prediction models which can be applied in the clinical setting. We identified in total 14 models for screening, 38 diagnostic models for detecting COVID-19 and 50 prognostic models for predicting ICU need, ventilator need, mortality risk, severity assessment or hospital length stay. Moreover, 43 studies were based on medical imaging and 58 studies on the use of clinical parameters, laboratory results or demographic features. Several heterogeneous predictors derived from multimodal data were identified. Analysis of these multimodal data, captured from various sources, in terms of prominence for each category of the included studies, was performed. Finally, Risk of Bias (RoB) analysis was also conducted to examine the applicability of the included studies in the clinical setting and assist healthcare providers, guideline developers, and policymakers.

Baseline Arterial CO2 Pressure Regulates Acute Intermittent Hypoxia-Induced Phrenic Long-Term Facilitation in Rats.

Moderate acute intermittent hypoxia (mAIH) elicits a progressive increase in phrenic motor output lasting hours post-mAIH, a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). mAIH-induced pLTF is initiated by activation of spinally-projecting raphe serotonergic neurons during hypoxia and subsequent serotonin release near phrenic motor neurons. Since raphe serotonergic neurons are also sensitive to pH and CO2, the prevailing arterial CO2 pressure (PaCO2) may modulate their activity (and serotonin release) during hypoxic episodes. Thus, we hypothesized that changes in background PaCO2 directly influence the magnitude of mAIH-induced pLTF. mAIH-induced pLTF was evaluated in anesthetized, vagotomized, paralyzed and ventilated rats, with end-tidal CO2 (i.e., a PaCO2 surrogate) maintained at: (1) ≤39 mmHg (hypocapnia); (2) ∼41 mmHg (normocapnia); or (3) ≥48 mmHg (hypercapnia) throughout experimental protocols. Although baseline phrenic nerve activity tended to be lower in hypocapnia, short-term hypoxic phrenic response, i.e., burst amplitude (Δ = 5.1 ± 1.1 µV) and frequency responses (Δ = 21 ± 4 bpm), was greater than in normocapnic (Δ = 3.6 ± 0.6 µV and 8 ± 4, respectively) or hypercapnic rats (Δ = 2.0 ± 0.6 µV and -2 ± 2, respectively), followed by a progressive increase in phrenic burst amplitude (i.e., pLTF) for at least 60 min post mAIH. pLTF in the hypocapnic group (Δ = 4.9 ± 0.6 µV) was significantly greater than in normocapnic (Δ = 2.8 ± 0.7 µV) or hypercapnic rats (Δ = 1.7 ± 0.4 µV). In contrast, although hypercapnic rats also exhibited significant pLTF, it was attenuated versus hypocapnic rats. When pLTF was expressed as percent change from maximal chemoreflex stimulation, all pairwise comparisons were found to be statistically significant (p < 0.05). We conclude that elevated PaCO2 undermines mAIH-induced pLTF in anesthetized rats. These findings contrast with well-documented effects of PaCO2 on ventilatory LTF in awake humans.

Interstitial lung opacities in patients with severe COVID-19 pneumonia by bedside high-resolution ultrasound in association to CO2 retention.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress syndrome (ARDS). OBJECTIVE: This single centre cross-section study aimed to grade the severity of pneumonia by bed-side lung ultrasound (LUS). METHODS: A scoring system discriminates 5 levels of lung opacities: A-lines (0 points),≥3 B-line (1 point), coalescent B-lines (2 points), marked pleural disruptions (3 points), consolidations (4 points). LUS (convex 1-5 MHz probe) was performed at 6 defined regions for each hemithorax either in supine or prone position. A lung aeration score (LAS, maximum 4 points) was allocated for each patient by calculating the arithmetic mean of the examined lung areas. Score levels were correlated with ventilation parameters and laboratory markers. RESULTS: LAS of 20 patients with ARDS reached from 2.58 to 3.83 and was highest in the lateral right lobe (Mean 3.67). Ferritin levels (Mean 1885µg/l; r = 0.467; p = 0.051) showed moderate correlation in spearman roh calculation. PaCO2 level (Mean 46.75 mmHg; r = 0.632; p = 0.005) correlated significantly with LAS, while duration of ventilation, Horovitz index, CRP, LDH and IL-6 did not. CONCUSIONS: The proposed LAS describes severity of lung opacities in COVID-19 patients and correlates with CO2 retention in patients with ARDS.

Effects of hypercapnia in sepsis: A scoping review of clinical and pre-clinical data.

BACKGROUND: Perform a scoping review of (1) pre-clinical studies testing the physiological effects of higher PaCO2 levels in the setting of sepsis models and (2) clinical investigations testing the effects of hypercapnia on clinical outcomes in mechanically ventilated patients with sepsis. METHODS: We performed a search of CENTRAL, PUBMED, CINAHL, and EMBASE. Study inclusion criteria for pre-clinical studies were: (1) bacterial sepsis model (2) measurement of PaCO2 , and (3) comparison of outcome measure between different PaCO2 levels. Inclusion criteria for clinical studies were: (1) diagnosis of sepsis, (2) receiving invasive mechanical ventilation, (3) measurement of PaCO2 , and (4) comparison of outcomes between different PaCO2 levels. We performed a qualitative analysis to collate and summarize the physiological and clinical effects of hypercapnia according to the recommended methodology from the Cochrane Handbook. RESULTS: Fifteen pre-clinical and nine clinical studies were included. Among pre-clinical studies, the individual studies found higher PaCO2 augments tissue blood flow and oxygenation, and attenuates inflammation and lung injury; however, all pre-clinical studies were found to have some degree of risk of bias. Six of the nine clinical studies were deemed to be good quality. Among clinical studies hypercapnia was associated with increased cerebral perfusion and oxygenation; however, there were conflicting results testing the association between hypercapnia and mortality. CONCLUSION: While individual pre-clinical studies identified potential mechanisms by which changes in PaCO2 levels could affect pathophysiology in sepsis, there is a paucity of clinical data as to the optimal PaCO2 range, demonstrating a need for future research. REGISTRATION: PROSPERO number CRD42018086703.

Temporal Evolution of the PcvCO2-PaCO2/CaO2-CcvO2 Ratio vs Serum Lactate during Resuscitation in Septic Shock.

BACKGROUND: Lactate as a target for resuscitation in patients with septic shock has important limitations. The PcvCO2-PaCO2/CaO2-CcvO2 ratio may be used as an alternative for the same. The primary outcome of the study is to evaluate the correlation between serum lactate and PcvCO2-PaCO2/CaO2-CcvO2 ratio measured at various time points to a maximum of 24 hours in patients with septic shock [mean arterial pressure (MAP) <65 mm Hg]. The secondary outcomes were to study the (1) relationship between the PcvCO2-PaCO2/CaO2-CcvO2 ratio and lactate clearance at 6, 12, and 24 hours as compared to the initial serum lactate, (2) to ascertain whether the PcvCO2-PaCO2/CaO2-CcvO2 ratio and the arterial lactate levels in the first 24 hours are able to predict mortality at day 28 of enrollment, and (3) to determine whether the PcvCO2-PaCO2/ CaO2-CcvO2 ratio and arterial lactate are useful in discriminating survivors from nonsurvivors. MATERIALS AND METHODS: Thirty patients with sepsis-induced hypotension who were being actively resuscitated were enrolled. Paired arterial and central venous blood samples were obtained 0.5 hourly till stabilization of MAP and 6 hourly thereafter for the first 24 hours. Patients were followed up to day 28 of enrollment for mortality and organ system failure. RESULTS: A positive correlation was observed between arterial lactate and PcvCO2-PaCO2/CaO2-CcvO2 ratio at 0, 6, 12, and 18 hours (R = 0.413, p = 0.02; R = 0.567, p = 0.001; R = 0.408, p = 0.025; R = 0.521, p = 0.003, respectively). No correlation was seen between PcvCO2-PaCO2/CaO2-CcvO2 ratio and lactate clearance. The subgroup analysis showed that PcvCO2-PaCO2/CaO2-CcvO2 ratio >1.696 at 24 hours of resuscitation predicted 28-day mortality (sensitivity: 80%, specificity 69.2%, area under the receiver operating characteristic curve 0.82). CONCLUSION: The PcvCO2-PaCO2/CaO2-CcvO2 ratio and lactate are positively correlated during the first 24 hours of active resuscitation from sepsis-induced hypotension, and a threshold of 1.696 mm Hg/mL/dL at 24 hours significantly differentiates survivors from nonsurvivors (CTRI/2017/11/010342). HOW TO CITE THIS ARTICLE: Madabhushi S, Trikha A, Anand RK, Ramachandran R, Singh PM, Rewari V. Temporal Evolution of the PcvCO2-PaCO2/CaO2-CcvO2 Ratio vs Serum Lactate during Resuscitation in Septic Shock. Indian J Crit Care Med 2021; 25(12):1370-1376.

Carbon Dioxide Sensing-Biomedical Applications to Human Subjects.

Carbon dioxide (CO2) monitoring in human subjects is of crucial importance in medical practice. Transcutaneous monitors based on the Stow-Severinghaus electrode make a good alternative to the painful and risky arterial "blood gases" sampling. Yet, such monitors are not only expensive, but also bulky and continuously drifting, requiring frequent recalibrations by trained medical staff. Aiming at finding alternatives, the full panel of CO2 measurement techniques is thoroughly reviewed. The physicochemical working principle of each sensing technique is given, as well as some typical merit criteria, advantages, and drawbacks. An overview of the main CO2 monitoring methods and sites routinely used in clinical practice is also provided, revealing their constraints and specificities. The reviewed CO2 sensing techniques are then evaluated in view of the latter clinical constraints and transcutaneous sensing coupled to a dye-based fluorescence CO2 sensing seems to offer the best potential for the development of a future non-invasive clinical CO2 monitor.

Mesalazine-induced lung injury with severe respiratory failure successfully treated with steroids and non-invasive positive pressure ventilation.

Drug-induced lung injury (DLI) has become more common because of the increasing number of therapeutic agents in use. Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is one of the key drugs for the treatment of ulcerative colitis (UC). Although mesalazine-induced lung injury has been previously reported, few cases have included severe respiratory failure. In this report, we present a case of mesalazine-induced lung injury with severe respiratory failure, which was improved by discontinuation of mesalazine and introduction of corticosteroid therapy and ventilation support with non-invasive positive pressure ventilation (NPPV). We also review the previous literature on mesalazine-induced lung injury.