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

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

Acid Base Disorders in Cirrhosis.

Metabolic and respiratory acid-base disorders are common in individuals with liver disease and cirrhosis. The most common disorder is respiratory alkalosis, which may be related to dyspnea or respiratory stimulation. Primary metabolic disorders are less common. Although the liver plays a role in metabolism of amino acids and generation of acid from dietary sources, it does not play a role in the regulation of pH. Instead, metabolic disorders may arise from alterations in normal metabolism or from medications, particularly diuretics and osmotic laxatives, used in the treatment of these complex patients. Understanding the mechanistic underpinnings of these disorders can aid in the management of individuals with liver disease in the hospital and in outpatient settings.

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.

Spectrum of Disorders associated with Tetany.

INTRODUCTION: Awareness regarding the etiological spectrum of tetany is poor among physicians. Because of poor awareness, tetany is underdiagnosed and undertreated. MATERIALS AND METHODS: Databases like PubMed, PubMed Central, Scopus, and Google Scholar are searched to identify peer-reviewed articles on tetany. Case reports, case series, and original articles are analyzed to identify different causes of tetany prevalent in the community. Different causes found are analyzed and tabulated, and finally, a flowchart is made on the approach for diagnosing different underlying pathologies of tetany. RESULTS: Both metabolic and respiratory alkalosis are important causes of tetany because of reduced ionized calcium levels. Gitelman syndrome (GS) is associated with metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria, and frequently causes normocalcemic tetany. Recurrent vomiting and primary hyperaldosteronism also cause tetany due to metabolic alkalosis. Hyperventilation syndrome (HVS) leads to respiratory alkalosis and is a frequent cause of tetany. Hyperventilation-induced tetany is also seen after spinal anesthesia and in respiratory disorders like asthma. Vitamin D deficiency (VDD), primary hypoparathyroidism, and pseudohypoparathyroidism (PHP) (1a, 1b, and 2) cause hypocalcemic tetany. Hypomagnesemia causes hypocalcemia and tetany due to peripheral parathyroid hormone resistance and impaired parathyroid hormone secretion. Drugs causing tetany include bisphosphonates, denosumab, cisplatin, antiepileptics, aminoglycosides, diuretics, etc. Tetany is also seen in acute pancreatitis, dengue, falciparum malaria, hyperemesis gravidarum, tumor lysis syndrome (TLS), massive blood transfusion, etc. Conclusion: The spectrum of disorders associated with tetany is diverse. Awareness of different causes will help early and proper diagnosis of tetany.

Rocuronium action can be affected by hyperventilation: a case report and computational simulation.

The neuromuscular blocking potency of rocuronium varies with respiratory pH changes, increasing at lower pH and decreasing at higher pH; thus, hyperventilation-induced respiratory alkalosis is expected to decrease the potency of rocuronium. We report a case of anesthetic management of modified electroconvulsive therapy (m-ECT) for a patient monitored with electromyography-based neuromuscular monitoring during two patterns of ventilation to elucidate their relationship and propose the possible mechanisms underlying the effects by computational simulations. Case presentation: The patient was a 25-year-old man with schizophrenia. In m-ECT, hyperventilation may be used to produce longer seizures. We compared the neuromuscular monitoring data recorded during hyperventilation and during normal ventilation while receiving the same dose of rocuronium. Despite receiving the same dose of rocuronium, the time required for the first twitch to decrease to 80% of the control value was delayed in hyperventilation compared to normal ventilation. Conclusions: This case report and computational simulation suggest that respiratory alkalosis might delay the action of rocuronium. It is necessary to consider the delayed action of rocuronium when hyperventilation is performed.

Critical Hypophosphatemia in a Special Operations Combat Dive Candidate: A Case Report.

In contrast to shallow water (hypoxic) blackout and swimming-induced pulmonary edema (SIPE), acute electrolyte disturbance secondary to acute respiratory alkalosis is not considered a common Combat Swimmer injury but has the potential to be life-threatening. We present the case of a 28-year-old Special Operations Dive Candidate who presented to the Emergency Department after a near-drowning incident with altered mental status, generalized weakness, respiratory distress, and tetany. He was found to have severe symptomatic hypophosphatemia (1.00mg/dL) and mild hypocalcemia secondary to intentional hyperventilation between subsurface "cross-overs," causing subsequent acute respiratory alkalosis. This is a unique presentation of a common electrolyte abnormality in a highly specialized population that is self-limiting when caused by acute respiratory alkalosis but poses a significant danger to Combat Swimmers if rescue personnel are not able to respond quickly.

Urine anion gap can differentiate respiratory alkalosis from metabolic acidosis in the absence of blood gas results.

INTRODUCTION: Low plasma bicarbonate concentration due to chronic respiratory alkalosis may be misdiagnosed as metabolic acidosis and mistreated with administration of alkali therapy, particularly when arterial blood gas is not available. METHODS: We measured urine anion gap [urine (Na+ + K+ ) - (Cl- )], as a surrogate of renal ammonium excretion in 15 patients presenting with hyperventilation and low serum bicarbonate concentration to distinguish chronic respiratory alkalosis (CRA) from metabolic acidosis (MA) when blood gas was unavailable. RESULTS: Hyperventilation and low serum bicarbonate concentrations were associated with urine pH above 5.5 and positive urine anion gap in all, suggesting CRA. The diagnosis was later confirmed by obtaining capillary blood gas, which showed a decrease in PCO2 and high normal pH values. CONCLUSION: The use of urine anion gap can help to differentiate between chronic respiratory alkalosis and metabolic acidosis, especially when arterial blood gas is not obtained.

Extreme alkalaemia with mixed alkalosis due to suspected acute-on-chronic respiratory alkalosis.

Herein we present a case of severe alkalaemia (pH 7.81) due to suspected acute-on-chronic respiratory alkalosis in a patient with chronic anxiety and metabolic alkalosis secondary to emesis. The patient was managed in the intensive care unit with significant improvement and discharged in stable condition. The case report emphasises considering a broad differential of aetiologies that can cause acid-base status derangements and identifying the appropriate therapeutic approach.

[Severe respiratory alkalosis due to psychogenic hyperventilation. Report of one case]. / Alcalosis respiratoria grave, la transformación de un cuadro funcional en orgánico. Caso clínico.

Severe respiratory alkalosis is a life-threatening condition, as it induces hypo- calcaemia and extreme adrenergic sensitivity leading to cerebral and myocardial vasoconstriction. We report a 37-year-old woman with previous consultations for a conversion disorder. While she was infected with SARS-CoV-2 (without pulmonary involvement), she consulted in the emergency room due to panic attacks. On admission, she developed a new conversion crisis with progressive clinical deterioration, hyperventilation, and severe respiratory alkalosis (pH 7.68, Bicarbonate 11.8 mEq/L and PaCO2 10 mmHg). Clinically, she was in a coma, with respiratory and heart rates 55 and 180 per min, a blood pressure of 140/90 mmHg, impaired perfusion (generalized lividity, distal coldness, and severe skin mottling) and tetany. She also had electrocardiographic changes and high troponin levels suggestive of ischemia, and hyperlactatemia. She was managed in the hospital with intravenous benzodiazepines. The clinical and laboratory manifestations resolved quickly, without the need for invasive measures and without systemic repercussions.

Acid-base disorders: A primer for clinicians.

An understanding of acid-base physiology is necessary for clinicians to recognize and correct problems that may negatively affect provision of nutrition support and drug therapy. An overview of acid-base physiology, the different acid-base disorders encountered in practice, a stepwise approach to evaluate arterial blood gases, and other key diagnostic tools helpful in formulating a safe and effective medical and nutrition plan are covered in this acid-base primer. Case scenarios are also provided for the application of principles and the development of clinical skills.

Global REACH 2018: Characterizing Acid-Base Balance Over 21 Days at 4,300 m in Lowlanders.

Steele, Andrew R., Philip N. Ainslie, Rachel Stone, Kaitlyn Tymko, Courtney Tymko, Connor A. Howe, David MacLeod, James D. Anholm, Christopher Gasho, and Michael M. Tymko. Global REACH 2018: characterizing acid-base balance over 21 days at 4,300 m in lowlanders. High Alt Med Biol. 23:185-191, 2022. Introduction: High altitude exposure results in hyperventilatory-induced respiratory alkalosis, followed by metabolic compensation to return arterial blood pH (pHa) toward sea level values. However, previous work has limited sample sizes, short-term exposure, and pharmacological confounders (e.g., acetazolamide). The purpose of this investigation was to characterize acid-base balance after rapid ascent to high altitude (i.e., 4,300 m) in lowlanders. We hypothesized that despite rapid bicarbonate ([HCO3-]) excretion during early acclimatization, partial respiratory alkalosis would still be apparent as reflected in elevations in pHa compared with sea level after 21 days of acclimatization to 4,300 m. Methods: In 16 (3 female) healthy volunteers not taking any medications, radial artery blood samples were collected and analyzed at sea level (150 m; Lima, Peru), and on days 1, 3, 7, 14, and 21 after rapid automobile (∼8 hours) ascent to high altitude (4,300 m; Cerro de Pasco, Peru). Results and Discussion: Although reductions in [HCO3-] occurred by day 3 (p < 0.01), they remained stable thereafter and were insufficient to fully normalize pHa back to sea level values over the subsequent 21 days (p < 0.01). These data indicate that only partial compensation for respiratory alkalosis persists throughout 21 days at 4,300 m.

Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats.

Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate absence seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics in the WAG/Rij rat, an established rodent model of absence epilepsy, we demonstrate that absence seizures are highly sensitive to arterial carbon dioxide, suggesting that seizure-generating circuits are sensitive to pH. Moreover, hyperventilation consistently activated neurons within the intralaminar nuclei of the thalamus, a structure implicated in seizure generation. We show that intralaminar thalamus also contains pH-sensitive neurons. Collectively, these observations suggest that hyperventilation activates pH-sensitive neurons of the intralaminar nuclei to provoke absence seizures.

Hyperventilation and Respiratory Alkalosis After Olanzapine for Insomnia: A Case Report.

Olanzapine is increasingly used as a sleep aid in hospitalized patients. Although thought to have less extrapyramidal effects, known side effects include oversedation, arrythmias, and hypotension. We present the unusual case of hyperventilation with respiratory alkalosis after the administration of olanzapine for insomnia in an elderly postoperative patient. This led to a second admission to the intensive care unit with invasive interventions including mechanical ventilation and vasopressor support. Caution must be exercised in prescribing antipsychotics for off-label use, especially in a population whose baseline characteristics can affect the pharmacokinetics of second-generation antipsychotics.

Bidirectional ventricular tachycardia induced by respiratory alkalosis mediated hypokalemia in a patient with acute ischemic heart failure.

Bidirectional ventricular tachycardia (BVT) is a rare arrhythmia that is generally observed in patients with catecholaminergic ventricular tachycardia or digoxin overdose. Herein, we present a case of BVT and electrical storm (ES) in an acute ischemic heart failure patient that is typically induced by hypokalemia. The patient was in invasive mechanical ventilator (MV) support and hypokalemia was related to acute respiratory alkalosis and that caused refractory hypokalemia despite intravenous (IV) potassium replacement. We also discuss our approach to solve refractory hypokalemia caused by respiratory alkalosis.

Stewart analysis unmasks acidifying and alkalizing effects of ionic shifts during acute severe respiratory alkalosis.

PURPOSE: Although both the Henderson-Hasselbalch method and the Stewart approach can be used to analyze acid-base disturbances and metabolic and respiratory compensation mechanisms, the latter may be superior in detecting subtle metabolic changes. MATERIALS AND METHODS: We analyzed acid-base disturbances using both approaches in six healthy male volunteers practicing extreme voluntary hyperventilation. Arterial blood gas parameters were obtained during a breathing exercise consisting of approximately 30 cycles of powerful hyperventilation followed by breath retention for approximately 2 min. RESULTS: Hyperventilation increased pH from 7.39 ± 0.01 at baseline to 7.74 ± 0.06, PaCO2 decreased from 34.1 ± 1.1 to 12.6 ± 0.7 mmHg, PaO2 increased from 116 ± 4.6 to 156 ± 4.3 mmHg. Baseline apparent strong ion difference was 42.3 ± 0.5 mEq/L, which decreased to 37.1 ± 0.7 mEq/L following hyperventilation. The strong ion gap significantly decreased following hyperventilation, with baseline levels of 10.0 ± 0.9 dropping to 6.4 ± 1.1 mEq/L. CONCLUSIONS: Henderson-Hasselbalch analysis indicated a profound and purely respiratory alkalosis with no metabolic compensation following extreme hyperventilation. The Stewart approach revealed metabolic compensation occurring within minutes. These results challenge the long-held axiom that metabolic compensation of acute respiratory acid-base changes is a slow process.

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.

Effect of induced acute metabolic alkalosis on the V̇E/V̇CO2 response to exercise in healthy adults.

We tested the hypothesis that increasing the respiratory control systems' arterial PCO2 equilibrium point via induced acute metabolic alkalosis by ingestion of sodium bicarbonate (NaHCO3, 0.3 g/kg) would decrease the ventilatory equivalent for CO2 (V̇E/V̇CO2) at its lowest point ("nadir") during constant-load cycle exercise testing performed at 80 % of peak power output in 18 healthy young adults. Compared to the sodium chloride (4 g) control condition, ingestion of NaHCO3: increased arterialized venous pH, HCO3- and PCO2 at rest by 0.05 ± 0.01 units (mean ± SE), 6.4 ± 0.4 mEq/L and 4.3 ± 0.7 mmHg, respectively (all p < 0.0001); and decreased the V̇E/V̇CO2 nadir during exercise by 9.4 % (p < 0.0001) secondary to a 4.7 ± 1.8 L/min decrease in V̇E (p = 0.019). In conclusion, induced acute metabolic alkalosis by ingestion of NaHCO3 decreased the V̇E/V̇CO2 response to strenuous exercise in healthy adults.

Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

Comparative analysis between available challenge tests in the hyperventilation syndrome.

BACKGROUND: The hyperventilation syndrome (HVS) is characterized by somatic/ psychological symptoms due to sustained hypocapnia and respiratory alkalosis without any organic disease. OBJECTIVE: The purpose of this study was to compare ventilatory parameters and symptoms reproducibility during the hyperventilation provocation test (HVPT) and cardiopulmonary exercise test (CPET) as diagnostic tools in patients with HVS, and to identify the most frequent etiologies of the HVS by a systematic assessment. METHODS: After exclusion of organic causes, 59 patients with HVS according to Nijmegen's questionnaire (NQ) score ≥23 with associated hypocapnia (PaCO2/PETCO2<35 mm Hg) were studied. RESULTS: The most frequent comorbidities of HVS were anxiety and asthma (respectively 95% and 73% of patients). All patients described ≥3 symptoms of NQ during the HVPT vs 14% of patients during the CPET (p<0.01). For similar maximal ventilation (61 L/min during HVPT vs 60 L/min during CPET), the median level of PETCO2 decreased from 30 mmHg at baseline to 15 mmHg during hyperventilation and increased from 31 mmHg at baseline to 34 mmHg at peak exercise (all p<0.01). No significant difference for the ventilatory parameters was found between patients with HVS (n = 16) and patients with HVS + asthma (n = 43). CONCLUSIONS: In term of symptoms reproducibility, HVPT is a better diagnostic tool than CPET for HVS. An important proportion of patients with HVS has an atypical asthma previously misdiagnosed. The exercise-induced hyperventilation did not induce abnormal reduction in PETCO2, suggesting that the exercise could be a therapeutic tool in HVS.

COVID-19 myocarditis and postinfection Bell's palsy.

Here we present the case of a 37-year-old previously healthy man who developed fever, headache and a unilateral, painful neck swelling while working offshore. He had no known contact with anyone with COVID-19; however, due to the ongoing pandemic, a nasopharyngeal swab was performed, which was positive for the virus. After transfer to hospital for assessment his condition rapidly deteriorated, requiring admission to intensive care for COVID-19 myocarditis. One week after discharge he re-presented with unilateral facial nerve palsy. Our case highlights an atypical presentation of COVID-19 and the multifaceted clinical course of this still poorly understood disease.