Mechanisms and Consequences of Oxygen and Carbon Dioxide Sensing in Mammals.

Molecular oxygen (O2) and carbon dioxide (CO2) are the primary gaseous substrate and product of oxidative phosphorylation in respiring organisms, respectively. Variance in the levels of either of these gasses outside of the physiological range presents a serious threat to cell, tissue, and organism survival. Therefore, it is essential that endogenous levels are monitored and kept at appropriate concentrations to maintain a state of homeostasis. Higher organisms such as mammals have evolved mechanisms to sense O2 and CO2 both in the circulation and in individual cells and elicit appropriate corrective responses to promote adaptation to commonly encountered conditions such as hypoxia and hypercapnia. These can be acute and transient nontranscriptional responses, which typically occur at the level of whole animal physiology or more sustained transcriptional responses, which promote chronic adaptation. In this review, we discuss the mechanisms by which mammals sense changes in O2 and CO2 and elicit adaptive responses to maintain homeostasis. We also discuss crosstalk between these pathways and how they may represent targets for therapeutic intervention in a range of pathological states.

Carbogen-Induced Respiratory Acidosis Blocks Experimental Seizures by a Direct and Specific Inhibition of NaV1.2 Channels in the Axon Initial Segment of Pyramidal Neurons.

Brain pH is a critical factor for determining neuronal activity, with alkalosis increasing and acidosis reducing excitability. Acid shifts in brain pH through the breathing of carbogen (5% CO2/95% O2) reduces seizure susceptibility in animal models and patients. The molecular mechanisms underlying this seizure protection remain to be fully elucidated. Here, we demonstrate that male and female mice exposed to carbogen are fully protected from thermogenic-triggered seizures. Whole-cell patch-clamp recordings revealed that acid shifts in extracellular pH (pHo) significantly reduce action potential firing in CA1 pyramidal neurons but did not alter firing in hippocampal inhibitory interneurons. In real-time dynamic clamp experiments, acidification reduced simulated action potential firing generated in hybrid model neurons expressing the excitatory neuron predominant NaV1.2 channel. Conversely, acidification had no effect on action potential firing in hybrid model neurons expressing the interneuron predominant NaV1.1 channel. Furthermore, knockdown of Scn2a mRNA in vivo using antisense oligonucleotides reduced the protective effects of carbogen on seizure susceptibility. Both carbogen-mediated seizure protection and the reduction in CA1 pyramidal neuron action potential firing by low pHo were maintained in an Asic1a knock-out mouse ruling out this acid-sensing channel as the underlying molecular target. These data indicate that the acid-mediated reduction in excitatory neuron firing is mediated, at least in part, through the inhibition of NaV1.2 channels, whereas inhibitory neuron firing is unaffected. This reduction in pyramidal neuron excitability is the likely basis of seizure suppression caused by carbogen-mediated acidification.SIGNIFICANCE STATEMENT Brain pH has long been known to modulate neuronal excitability. Here, we confirm that brain acidification reduces seizure susceptibility in a mouse model of thermogenic seizures. Extracellular acidification reduced excitatory pyramidal neuron firing while having no effect on interneuron firing. Acidification also reduced dynamic clamp firing in cells expressing the NaV1.2 channel but not in cells expressing NaV1.1 channels. In vivo knockdown of Scn2a mRNA reduced seizure protection of acidification. In contrast, acid-mediated seizure protection was maintained in the Asic1a knock-out mouse. These data suggest NaV1.2 channel as an important target for acid-mediated seizure protection. Our results have implications on how natural variations in pH can modulate neuronal excitability and highlight potential antiseizure drug development strategies based on the NaV1.2 channel.

Acute sodium bicarbonate administration improves ventilatory efficiency in experimental respiratory acidosis: clinical implications.

Administering sodium bicarbonate (NaHCO3) to patients with respiratory acidosis breathing spontaneously is contraindicated because it increases carbon dioxide load and depresses pulmonary ventilation. Nonetheless, several studies have reported salutary effects of NaHCO3 in patients with respiratory acidosis but the underlying mechanism remains uncertain. Considering that such reports have been ignored, we examined the ventilatory response of unanesthetized dogs with respiratory acidosis to hypertonic NaHCO3 infusion (1 N, 5 mmol/kg) and compared it with that of animals with normal acid-base status or one of the remaining acid-base disorders. Ventilatory response to NaHCO3 infusion was evaluated by examining the ensuing change in PaCO2 and the linear regression of the PaCO2 vs. pH relationship. Strikingly, PaCO2 failed to increase and the ΔPaCO2 vs. ΔpH slope was negative in respiratory acidosis, whereas PaCO2 increased consistently and the ΔPaCO2 vs. ΔpH slope was positive in the remaining study groups. These results cannot be explained by differences in buffering-induced decomposition of infused bicarbonate or baseline levels of blood pH, PaCO2, and pulmonary ventilation. We propose that NaHCO3 infusion improved the ventilatory efficiency of animals with respiratory acidosis, i.e., it decreased their ratio of total pulmonary ventilation to carbon dioxide excretion (VE/VCO2). Such exclusive effect of NaHCO3 infusion in animals with respiratory acidosis might emanate from baseline increased VD/VT (dead space/tidal volume) caused by bronchoconstriction and likely reduced pulmonary blood flow, defects that are reversed by alkali infusion. Our observations might explain the beneficial effects of NaHCO3 reported in patients with acute respiratory acidosis.

Aminopyridines Restore Ventilation and Reverse Respiratory Acidosis at Late Stages of Botulism in Mice.

Botulinum neurotoxin (BoNT) is a potent protein toxin that causes muscle paralysis and death by asphyxiation. Treatments for symptomatic botulism are intubation and supportive care until respiratory function recovers. Aminopyridines have recently emerged as potential treatments for botulism. The clinically approved drug 3,4-diaminopyridine (3,4-DAP) rapidly reverses toxic signs of botulism and has antidotal effects when continuously administered in rodent models of lethal botulism. Although the therapeutic effects of 3,4-DAP likely result from the reversal of diaphragm paralysis, the corresponding effects on respiratory physiology are not understood. Here, we combined unrestrained whole-body plethysmography (UWBP) with arterial blood gas measurements to study the effects of 3,4-DAP, and other aminopyridines, on ventilation and respiration at terminal stages of botulism in mice. Treatment with clinically relevant doses of 3,4-DAP restored ventilation in a dose-dependent manner, producing significant improvements in ventilatory parameters within 10 minutes. Concomitant with improved ventilation, 3,4-DAP treatment reversed botulism-induced respiratory acidosis, restoring blood levels of CO2, pH, and lactate to normal physiologic levels. Having established that 3,4-DAP-mediated improvements in ventilation were directly correlated with improved respiration, we used UWBP to quantitatively evaluate nine additional aminopyridines in BoNT/A-intoxicated mice. Multiple aminopyridines were identified with comparable or enhanced therapeutic efficacies compared with 3,4-DAP, including aminopyridines that selectively improved tidal volume versus respiratory rate and vice versa. In addition to contributing to a growing body of evidence supporting the use of aminopyridines to treat clinical botulism, these data lay the groundwork for the development of aminopyridine derivatives with improved pharmacological properties. SIGNIFICANCE STATEMENT: There is a critical need for fast-acting treatments to reverse respiratory paralysis in patients with botulism. This study used unrestrained, whole-body plethysmography and arterial blood gas analysis to show that aminopyridines rapidly restore ventilation and respiration and reverse respiratory acidosis when administered to mice at terminal stages of botulism. In addition to supporting the use of aminopyridines as first-line treatments for botulism symptoms, these data are expected to contribute to the development of new aminopyridine derivatives with improved pharmacological properties.

Short-term exposure to high pCO2 leads to decreased branchial cytochrome C oxidase activity in the presence of octopamine in a decapod.

In a recent mechanistic study, octopamine was shown to promote proton transport over the branchial epithelium in green crabs, Carcinus maenas. Here, we follow up on this finding by investigating the involvement of octopamine in an environmental and physiological context that challenges acid-base homeostasis, the response to short-term high pCO2 exposure (400 Pa) in a brackish water environment. We show that hyperregulating green crabs experienced a respiratory acidosis as early as 6 h of exposure to hypercapnia, with a rise in hemolymph pCO2 accompanied by a simultaneous drop of hemolymph pH. The slightly delayed increase in hemolymph HCO3- observed after 24 h helped to restore hemolymph pH to initial values by 48 h. Circulating levels of the biogenic amine octopamine were significantly higher in short-term high pCO2 exposed crabs compared to control crabs after 48 h. Whole animal metabolic rates, intracellular levels of octopamine and cAMP, as well as branchial mitochondrial enzyme activities for complex I + III and citrate synthase were unchanged in posterior gill #7 after 48 h of hypercapnia. However, application of octopamine in gill respirometry experiments suppressed branchial metabolic rate in posterior gills of short-term high pCO2 exposed animals. Furthermore, branchial enzyme activity of cytochrome C oxidase decreased in high pCO2 exposed crabs after 48 h. Our results indicate that hyperregulating green crabs are capable of quickly counteracting a hypercapnia-induced respiratory acidosis. The role of octopamine in the acclimation of green crabs to short-term hypercapnia seems to entail the alteration of branchial metabolic pathways, possibly targeting mitochondrial cytochrome C in the gill. Our findings help advancing our current limited understanding of endocrine components in hypercapnia acclimation. SUMMARY STATEMENT: Acid-base compensation upon short-term high pCO2 exposure in hyperregulating green crabs started after 6 h and was accomplished by 48 h with the involvement of the biogenic amine octopamine, accumulation of hemolymph HCO3-, and regulation of mitochondrial complex IV (cytochrome C oxidase).

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.

Respiratory acidosis induced ST-segment elevation.

Acidosis has been reported to cause ST-segment elevation. We presented a woman with a history of rectal adenocarcinoma experienced cardiac arrest during the contrast-enhanced computed tomography examination. When spontaneous circulation returned, arterial blood gas revealed she had severe respiratory acidosis, and bedside electrocardiogram showed ST-segment elevation in anterior precordial leads. Emergent coronary angiography was normal. Echocardiography revealed no abnormality of cardiac cavity size, segmental wall motion, or pericardial echo. Carcinoma metastasis in the peritoneal cavity and lungs was detected on the contrast-enhanced computed tomography scan while the heart was not involved. The ST-segment regressed and the respiratory acidosis was corrected after she received mechanical ventilation which strongly suggested the association between acidosis and the electrocardiogram changes.

The role of the ADVanced Organ Support (ADVOS) system in critically ill patients with multiple organ failure.

BACKGROUND: Multi-organ failure characterized by acute kidney injury, liver dysfunction, and respiratory failure is a complex condition associated with high mortality, for which multiple individual support devices may be simultaneously required. This review aims to appraise the current evidence for the ADVanced Organ Support (ADVOS) system, a novel device integrating liver, lung, and kidney support with blood detoxification. METHODS: We performed a literature review of the PubMed database to identify human and animal studies evaluating the ADVOS system. RESULTS: In porcine models of acute liver injury and small clinical studies in humans, ADVOS significantly enhanced the elimination of water-soluble and protein-bound toxins and metabolites, including creatinine, ammonia, blood urea nitrogen, and lactate. Cardiovascular parameters (mean arterial pressure, cerebral perfusion pressure, and cardiac index) and renal function were improved. ADVOS clears carbon dioxide (CO2 ) effectively with rapid correction of pH abnormalities, achieving normalization of CO2 , and bicarbonate levels. In patients with COVID-19 infection, ADVOS enables rapid correction of acid-base disturbance and respiratory acidosis. ADVOS therapy reduces mortality in multi-organ failure and has been shown to be safe with minimal adverse events. CONCLUSIONS: From the small observational studies analyzed, ADVOS demonstrates excellent detoxification of water-soluble and protein-bound substances. In particular, ADVOS permits the correction of metabolic and respiratory acidosis through the fluid-based direct removal of acid and CO2 . ADVOS is associated with significant improvements in hemodynamic and biochemical parameters, a trend toward improved survival in multi-organ failure, and is well-tolerated. Larger randomized trials are now necessary to further validate these encouraging results.

It is unlikely that oxygen supplementation in COPD patients with chronic respiratory failure reduce cardiac troponin level.

BACKGROUND: Cardiac troponin T (cTnT) is a biomarker of myocardial injury frequently elevated in COPD patients, potentially because of hypoxemia. This non-randomised observational study investigates whether long-term oxygen treatment (LTOT) reduces the cTnT level. METHODS: We compared cTnT between COPD patients who were candidates for LTOT (n = 20) with two reference groups. Patients from both reference groups were matched with the index group using propensity score.Reference groups consists of institutional pulmonary rehabilitation patients (short-term group) (n = 105 after matching n = 11) and outpatients at a pulmonary rehabilitation clinic (long-term group)(n = 62 after matching n = 10). Comparison was done within 24 h after LTOT initiation in first reference group and within 6 months after inclusion in the second group. RESULTS: The geometric mean of (standard deviation in parentheses) cTnT decreased from 17.8 (2.3) ng/L (between 8 and 9 a.m.) to 15.4 (2.5) ng/L between 1 and 2 p.m. in the LTOT group, and from 18.4 (4.8) ng/L to15.4 (2.5) ng/L in group (1) The corresponding long-term results were 17.0 (2.9) ng/L at inclusion (between 10 and 12 a.m.) to 18.4 (2.4) ng/L after 3 months in the LTOT-group, and from 14.0 (2.4) ng/L to 15.4 (2.5) ng/L after 6 months in group (2) None of the differences in cTnT during the follow-up between the LTOT-group and their matched references were significant. CONCLUSION: Initiation of LTOT was not associated with an early or sustained reduction in cTnT after treatment with oxygen supplementation.

The prevalence of non-invasive ventilation and long-term oxygen treatment in Helsinki University Hospital area, Finland.

BACKGROUND: Chronic respiratory failure (CRF) can be treated at home with non-invasive ventilation (NIV) and/or long-term oxygen (LTOT). The prevalence of these treatments is largely unknown. We aimed to clarify the prevalence and indications of the treatments, and the three-year mortality of the treated patients in the Helsinki University Hospital (HUH) area in Finland. METHODS: In this retrospective study we analyzed the prevalence of adult CRF patients treated with NIV and/or LTOT on 1.1.2018 and followed these patients until 1.1.2021. Data collected included the underlying diagnosis, patient characteristics, information on treatment initiation and from the last follow-up visit, and mortality during the three-year follow-up. Patients with home invasive mechanical ventilation or sleep apnea were excluded. RESULTS: On 1.1.2018, we had a total of 815 patients treated with NIV and/or LTOT in the Helsinki University Hospital (HUH) area, with a population of 1.4 million. The prevalence of NIV was 35.4 per 100,000, of LTOT 24.6 per 100,000 and of the treatments combined 60.0 per 100,000. Almost half, 44.5%, were treated with NIV, 41.0% with LTOT, and 14.4% underwent both. The most common diagnostic groups were chronic obstructive pulmonary disease (COPD) (33.3%) and obesity-hypoventilation syndrome (OHS) (26.6%). The three-year mortality in all patients was 45.2%. In the COPD and OHS groups the mortality was 61.3% and 21.2%. In NIV treated patients, the treatment durations varied from COPD patients 5.3 years to restrictive chest wall disease patients 11.4 years. The age-adjusted Charlson co-morbidity index (ACCI) median for all patients was 3.0. CONCLUSIONS: NIV and LTOT are common treatments in CRF. The prevalence in HUH area was comparable to other western countries. As the ACCI index shows, the treated patients were fragile, with multiple co-morbidities, and their mortality was high. Treatment duration and survival vary greatly depending on the underlying diagnosis.

Outcomes of Minority COVID-19 patients managed with ECMO: A single-center experience.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly burdened the global healthcare system since December 2019. Minority populations are found to have a higher incidence of hospitalization and higher mortality when compared to Caucasians. Extracorporeal membrane oxygenation (ECMO) is reserved for COVID-19 patients who develop respiratory failure refractory to conventional management. To our knowledge, no data has been reported on outcome differences between Minority COVID-19 patients and Caucasian COVID-19 patients managed with ECMO. We aimed to investigate the outcome differences between these two groups. METHODS: Our retrospective cohort study had 23 adults (aged 18 and older) diagnosed with COVID-19 by polymerase chain reaction. All patients developed acute respiratory distress syndrome (ARDS), refractory to conventional treatment, and were managed on ECMO support. The primary outcome of interest was mortality; the secondary outcome was the rate of ECMO-related complications. RESULTS: The overall mortality rate of our study was higher (70%) than other reports of the COVID-19 population on ECMO. Caucasians in our study had more severe respiratory acidosis with carbon dioxide retention and appeared to have a higher mortality rate of 85.7% compared to Minorities (62.5%). No differences in complication rates between these two groups were identified. CONCLUSIONS: Our cohort revealed a high overall mortality rate of COVID-19 patients on ECMO support. The Caucasian group was observed to have higher mortality than the Minority group. The high overall mortality was likely attributed to the Caucasian group, which had more severe respiratory acidosis before ECMO initiation, a known predictor of poor prognosis in ARDS patients. Our cohort's ethnic composition may also partially explain the high mortality rate since COVID-19 Minorities are reported to have worse outcomes than Caucasians. Larger and randomized studies are needed to investigate further the mortality and complication differences between Minority and Caucasian patients diagnosed with COVID-19 and managed by ECMO.

6-Year-Old Male Drowning Complicated by Cardiac Arrest and Ensuing Metabolic and Respiratory Acidosis: Should Presence of Pulses Lead Clinicians to Pursue Prolonged Cardiopulmonary Resuscitation?

BACKGROUND: Drowning is one of the leading causes of death in the pediatric population. Patients arriving to the emergency department (ED) with submersion injuries are often asymptomatic and well-appearing, but can sometimes present critically ill and require prolonged resuscitation. The question of how long to continue resuscitation of a pediatric patient with a submersion injury is a difficult question to answer. CASE REPORT: We present a case of 6-year-old boy was found by his friends submerged in sea water for 10-15 min. The patient was rescued by lifeguards and evaluated by emergency medical personnel, who found him breathing spontaneously but unresponsive. En route to hospital, the patient became apneic, cardiopulmonary resuscitation (CPR) was started, and the patient was intubated. The patient arrived to the ED in cardiopulmonary arrest, CPR was continued and epinephrine was administered. Return of spontaneous circulation was achieved after 42 min in the ED. Initial laboratory test results showed severe acidosis and chest x-ray study showed diffuse interstitial edema. Ventilator settings were adjusted in accordance with lung protective ventilation strategies and the acidosis began to improve. Over the next several days, the patient was weaned to noninvasive ventilation modalities and eventually made a complete neurologic recovery and continued to be a straight-A student. Why Should an Emergency Physician Be Aware of This?We make the case that, in select drowning patients, duration of CPR longer than 30 min can potentially result in favorable neurologic outcomes. Prolonged CPR should be especially strongly considered in patients with a pulse at any point during evaluation. With the combination of prolonged CPR and judicious use of lung protective mechanical ventilation strategies, we were able to successfully treat the patient in our case.

Agreement between arterial and central venous blood pH and its contributing variables in anaesthetized dogs with respiratory acidosis.

OBJECTIVE: To determine the accuracy of variables that influence blood pH, obtained from central venous (jugular vein) blood samples compared with arterial (dorsal pedal artery) samples in anaesthetized dogs with respiratory acidosis. STUDY DESIGN: Prospective, comparative, observational study. ANIMALS: A group of 15 adult male dogs of various breeds weighing 17 (11-42) kg [median (range)]. METHODS: Dogs were premedicated with buprenorphine (0.03 mg kg-1) and medetomidine (0.01 mg kg-1) administered intramuscularly by separate injections, anaesthetized with propofol intravenously to effect and maintained with isoflurane in 50% air-oxygen. Arterial and central venous catheters were placed. After 15 minutes of spontaneous breathing, arterial and central venous blood samples were obtained and analysed within 5 minutes, using a bench-top gas analyser. Differences between arterial and central venous pH and measured variables were assessed using Wilcoxon rank sum test and effect size (r: matched-pairs rank-biserial correlation) was calculated for each comparison. The agreement (bias and limits of agreement: LoAs) between arterial and central venous pH and measured variables were assessed using Bland-Altman; p < 0.05. Data are reported as median and 95% confidence interval. RESULTS: Arterial blood pH was 7.23 (7.19-7.25), and it was significantly greater than central venous samples 7.21 (7.18-7.22; r = 0.41). Agreement between arterial and venous pH was acceptable with a bias of 0.01 (0.002-0.02) and narrow LoAs. PCO2 [arterial 54 (53-58) mmHg, 7.2 (7.1-7.7) kPa; venous 57 (54-62) mmHg, 7.6 (7.2-8.3) kPa], bicarbonate ion concentration and base excess did not differ between samples; however, agreement between arterial and venous PCO2 was not acceptable with a bias of -2 (-5 to 0) mmHg and wide LoAs. CONCLUSIONS AND CLINICAL RELEVANCE: Blood pH measured from central venous (jugular vein) blood is an acceptable clinical alternative to arterial blood (dorsal pedal artery) in normovolaemic anaesthetized dogs with respiratory acidosis.

Arterial Blood Gas and Rotational Thromboelastometry Parameters in Healthy Rescuers Incidentally Exposed to Nitroglycerin, Nitrogen Compounds, and Combustion Products.

INTRODUCTION: Acute exposure to nitrogen compounds combined with a massive inhalation of air pollutants can influence respiratory and cardiovascular symptoms and coagulation abnormalities in accidentally exposed healthy adults during cave detonation operations. METHODS: Italian alpine and cave rescuers widened a cave in the Abisso Luca Kralj in Trieste, Italy. Volunteers inside the cave were accidentally exposed to the fumes from an uncontrolled detonation of blasting gelatin microcharges. We performed a retrospective cohort study on the clinical data, arterial blood gas analysis, and rotational thromboelastometry parameters from the rescuers involved in the accident. RESULTS: Ninety-three healthy rescuers were involved in the uncontrolled detonation: 47 volunteers handled a mixture of nitrogen compounds (blaster group), and 46 volunteers did not (nonblaster group). After the accident, statistically significant differences (P<0.05) in arterial blood gas values were observed between the groups, with a pattern of mild respiratory acidosis with hypercapnia in the nonblaster group and severe mixed acid-base disorder with hypoxia and hypercapnia in the blaster group. Mild hyperfibrinolysis was observed in 44 volunteers in the blaster group, as were associated bleeding symptoms in 34 volunteers; no significant coagulation modifications were recorded in the nonblaster group. CONCLUSIONS: Respiratory acidosis with hypoxia, hypercapnia, a compensatory metabolic response, and mild hyperfibrinolysis were probably related to the combined effect of nitrogen compounds and the inhaled toxic products of detonation. Therefore, each element exerts a determinant effect on promoting the biological toxicity of the others.

Acute and long-term management of severe bronchiectasis with high flow nasal therapy: A case report.

Bronchiectasis (BE) is a long-term, chronic lung condition featured by widened and scarred airways. These can alter the physiological mucociliary clearance, making it difficult to clear mucus and microorganisms, leading to frequent exacerbations. High flow nasal therapy (HFNT) is a noninvasive respiratory support that delivers heated and humidified gas eventually enriched with oxygen, through a nasal cannula.  Humidification is crucial for adequate airways mucociliary clearance, improving ciliary function and consequently reducing airways inflammation and recurrent infections. HFNT has been mostly used in patients with acute hypoxemic respiratory failure and in selected patients with chronic respiratory failure due to COPD. Still, evidence about its use in acute and long-term home setting in patients with clinically relevant BE are lacking. We report a case of severe widespread BE, already on top medical therapy and pulmonary rehabilitation, still suffering from difficult mucus expectoration and recurrent exacerbations, who has been additionally treated with HFNT, both in hospital and domiciliary, reporting significant improvements on relevant clinical and patient-centered outcomes. Thus, HFNT may confer additional benefits as an add-on treatment of patients with severe BE and respiratory failure.

Sodium bicarbonate therapy for acute respiratory acidosis.

PURPOSE OF REVIEW: Respiratory acidosis is commonly present in patients with respiratory failure. The usual treatment of hypercapnia is to increase ventilation. During the recent surge of COVID-19, respiratory acidosis unresponsive to increased mechanical ventilatory support was common. Increasing mechanical ventilation comes at the expense of barotrauma and hemodynamic compromise from increasing positive end-expiratory pressures or minute ventilation. Treating acute respiratory acidemia with sodium bicarbonate remains controversial. RECENT FINDINGS: There are no randomized controlled trials of administration of sodium bicarbonate for respiratory acidemia. A recent review concluded that alkali therapy for mixed respiratory and metabolic acidosis might be useful but was based on the conflicting and not conclusive literature regarding metabolic acidosis. This strategy should not be extrapolated to treatment of respiratory acidemia. Low tidal volume ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has beneficial effects associated with permissive hypercapnia. Whether the putative benefits will be negated by administration of alkali is not known. Hypercapnic acidosis is well tolerated, with few adverse effects as long as tissue perfusion and oxygenation are maintained. SUMMARY: There is a lack of clinical evidence that administration of sodium bicarbonate for respiratory acidosis has a net benefit; in fact, there are potential risks associated with it.

Dead in the air- The need to adapt to CoVID adaptations.

During the recent CoVID-19 pandemic, airway management recommendations have been provided to decrease aerosolization and risk of viral spread to healthcare providers. High efficiency particulate air (HEPA) viral filters and adaptors are one way to decrease the risk of aerosolization during intubation. When placed proximal to the ventilator circuit, these viral filters and adaptors can create a significant amount of dead space, which in our smallest patients can significantly impact effective ventilation. We report a case of hypoventilation in a pediatric patient due to lack of provider team appreciation or ventilator sensing of additional dead space due to HEPA viral filter and adaptor.

Salbutamol-induced lactic acidosis in status asthmaticus survivor.

BACKGROUND: Salbutamol-induced lactic acidosis is a rare presentation that could manifest in specific clinical context as acute asthmatic attack treatment. An increase of glycolysis pathway leading to pyruvate escalation is the mechanism of hyperlactatemia in ß2-adrenergic agonist drug. CASE PRESENTATION: A 40-year-old man who had poor-controlled asthma, presented with progressive dyspnea with coryza symptom for 6 days. He was intubated and admitted into medical intensive care unit due to deteriorated respiratory symptom. Severe asthmatic attack was diagnosed and approximate 1.5 canisters of salbutamol inhaler was administrated within 24 h of admission. Initial severe acidosis consisted of acute respiratory acidosis from ventilation-perfusion mismatch and acute metabolic acidosis resulting from bronchospasm and hypoxia-related lactic acidosis, respectively. The lactate level was normalized in 6 h after hypoxemia and ventilation correction. Given the lactate level re-elevated into a peak of 4.6 mmol/L without signs of tissue hypoxia nor other possible etiologies, the salbutamol toxicity was suspected and the inhaler was discontinued that contributed to rapid lactate clearance. The patient was safely discharged on the 6th day of admission. CONCLUSION: The re-elevation of serum lactate in status asthmaticus patient who had been administrated with the vast amount of ß2-adrenergic agonist should be considered for salbutamol-induced lactic acidosis and promptly discontinued especially when there were no common potentials.

Changes in acid-base status in oxygen toxicity at 230 kPa oxygen as a function of exposure time.

Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.

Role of esophageal manometry in polysomnography of patients with chronic respiratory failure.

Esophageal pressure (Pes) monitoring is performed during polysomnography (PSG) with a thin, water-filled catheter connected to a transducer. The resulting quantitative assessment of respiratory effort can aid in the accurate diagnosis of sleep-related breathing disorders. This was a prospective observational study using Pes in PSG for thirty patients with chronic respiratory failure (CRF) conducted in the Department of Pulmonary, Critical Care and Sleep Medicine at a tertiary care centre of North India. Sleep scoring was done by conventional method and using esophageal manometry and compared polysomnography normal without esophageal manometry recording (PSGN) and polysomnography with esophageal manometry scoring (PSGE). Apnea hypopnea index (AHI) index was similar in both groups. However, respiratory effort related arousals (RERAs) were diagnosed easily using Pes resulting in significant increase in respiratory disturbance index (RDI) and even reclassification in terms of severity of sleep apnea. Besides, Pes was also useful to distinguish obstructive from central hypopnea which cannot be distinguished by routine PSG which can help guide therapy particularly in chronic respiratory failure patients with hypoventilation. Such patients with hypoventilation often require bilevel positive airway pressure as ventilatory support. Central hypopneas and apneas with hypercapnia may require higher-pressure support, a backup rate or even advanced volume assured modes of ventilation. Thus, it can be concluded that Pes in PSG remains a safe and generally well-tolerated procedure. Use of Pes aids to detect RERA and thereby RDI; a better marker of sleep-related breathing disorder rather than AHI. It also helps in differentiating between obstructive and central hypopnea.