Pregnant and postpartum women have a higher risk for developing severe Covid-19 and other clinical and obstetric complications. This study aims to evaluate the frequency of metabolic acidosis with elevated anion gap and describe a case series of euglycemic ketoacidosis (EKA) in pregnant and postpartum women with severe confirmed or suspected Covid-19.

Observational retrospective study carried in a reference intensive care unit from May 2020 to June 2022. Cases were confirmed with positive RT-PCR or rapid antigen test. Cases with compatible clinical and radiologic findings were also included. Ketoacidosis was defined as the presence of metabolic acidosis with high anion gap (bicarbonate < 15 mEq/L and AG > 10 mEq/L) and ketonuria (2+ or more in urine test). Statistical analyses were made with R software.

Of 101 admissions, 61 (60.4%) presented metabolic acidosis with high anion gap. The median age was 29 years, and most were in the third trimester. Evolution to invasive mechanical ventilation (54.0%) and obstetric complications (78.0%) were frequent. The prevalence of metabolic acidosis with high anion gap and absence of hyperlactatemia was of 43.6% (44/101). Six (5.94%) women met the criteria for EKA. Despite severity, there were no deaths.

The prevalence of metabolic acidosis and EKA in pregnant and postpartum women with severe Covid-19 was high. This condition should be routinely, so it can be promptly treated.

Neuroblastomas represent a diverse group of neuroblastic tumors characterized by variability in their clinical progression and degree of differentiation. In rare cases, patients with neuroblastoma may present with paraneoplastic syndromes, such as watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome), linked to the secretion of vasoactive intestinal peptide (VIP). We report a case of a 14-month-old girl presented with a three-week history of watery diarrhea and signs of dehydration with no other symptoms. The patient's medical history was unremarkable, and no medication use was reported. Venous blood gas analysis revealed a normal anion gap metabolic acidosis with severe hypokalemia. The patient was referred to our hospital 48 hours post-admission due to persistent hypokalemic metabolic acidosis, unresponsive to intravenous fluid therapy. The primary causes of normal anion gap metabolic acidosis in young children are gastrointestinal bicarbonate loss due to diarrhea and renal bicarbonate loss. Semi-quantitative urine organic acid analysis, reported 48 hours after admission, revealed increased vanillylmandelic acid (VMA) (89 mmol/mol creatinine) and homovanillic acid (HVA) (21 mmol/mol creatinine), raising the suspicion of a neuroblastoma. Subsequent analysis of an acidified urine sample confirmed a more than threefold increase in VMA, HVA, normetanephrine, norepinephrine, and 3-methoxytyramine concentrations. In addition, VIP was markedly elevated (1994 ng/L) in a blood sample. The diagnosis of neuroblastoma was confirmed through imaging and histological examination. This case illustrates that chronic diarrhea with metabolic dysregulation (e.g. hypokalemia) can be the first and only symptom in patients with VIP-secreting neuroblastoma which can result in delayed diagnosis of neuroblastoma.

In clinical medicine, hyponatremia is highly prevalent and frequently misdiagnosed, leading to substantial mismanagement and iatrogenic morbidity. Its differential diagnosis includes numerous diseases with diverse etiologies, making accurate assessment challenging. Despite extensive literature and guidelines on hyponatremia, most patients do not receive adequate evaluation due to the limitations of diagnostic algorithms, which rely on low-value clinical signs and are unable to identify concurrent conditions. In this review, we examine the range of laboratory tests available for hyponatremia assessment. Understanding renal mechanisms of solute and water exchange (e.g., fractional excretion) is essential for selecting appropriate tests and interpreting their diagnostic value. Additionally, detailed electrolyte and acid-base assessments remain critical for establishing a definitive diagnosis. We comprehensively discuss the selection of laboratory tests for specific differential diagnoses of hyponatremia. Importantly, in cases of acute hyponatremia, rapid correction should take precedence over a complete diagnostic workup. Ultimately, a thorough understanding of laboratory evaluation is crucial for accurately diagnosing hyponatremia. This paper critically reviews the available literature and explores relevant diseases in the context of associated laboratory parameters.

Virtually every protein in our bodies binds protons, resulting in a specific electrical charge. If the surrounding proton concentration changes, such as in acidosis or alkalosis, the charge of the protein can change, as well, which in turn can affect protein folding and thus function. Therefore, disturbances of acid-base homeostasis can have serious clinical consequences, and for this reason, the blood pH is usually strictly controlled with the kidneys playing a major part in the long-term maintenance of acid-base homeostasis. Here we review alterations in blood pH that can occur as a side effect of medical treatments, with this first part discussing those resulting in acidosis.

Background/Objectives: Critically ill patients can often present acid-base alterations. The aim of this study was to evaluate the prevalence and the time-course of acid-base alterations on intensive care unit (ICU) admission and on day one by the traditional standard base excess (SBE)-based and the Stewart methods in mechanically ventilated patients. Methods: A prospective observational study enrolling mechanically ventilated patients in the ICU was conducted. Arterial blood gas analysis, blood and urine samples were obtained on ICU admission and on day one. Plasmatic and urinary acid-base variables were compared among acidemic, alkalemic and patients with normal pH. The agreement between the SBE-based and Stewart methods was assessed at ICU admission and on day one. Results: One hundred and seventy-two patients were enrolled. On ICU admission, 55 (32%), 29 (17%) and 88 (51%) patients had acidemia, alkalemia and a normal pH, respectively. On day one, 12 (7%), 48 (28%) and 112 (65%) patients had acidemia, alkalemia and a normal pH with lower values of paCO2 and albumin. According to the SBE and Stewart approaches, the occurrence of metabolic acidosis was similar (24% vs. 35%), as well as the rate of metabolic alkalosis (16% vs. 23%) on ICU admission; on day one, the occurrence of metabolic acidosis was different (12% vs. 35%), as well as the rate of metabolic alkalosis (35% vs. 14%). The agreement between methods was estimated to be low both on ICU admission and on day one. Conclusions: Up to 50 % of mechanically ventilated patients presented acid-base derangements, mainly due to acidemia on ICU admission and to alkalemia after 24 h, secondary to alterations in carbon dioxide and plasma albumin. The agreement between the traditional and Stewart approaches was poor. The Stewart approach could be more accurate in detecting the acid-base disturbances in critically ill patients characterized by changes of mechanical ventilation and fluid administration.

Although, COVID-19 has resulted in over 7 million deaths globally, many questions still remain about the risk factors for disease severity and the effects of variants and vaccinations over the course of the pandemic. To address this gap, we conducted a retrospective analysis of electronic health records from COVID-19 patients over 2.5 years of the COVID-19 pandemic to identify associated clinical features.

We analyze a retrospective cohort of 21,312 acute-care patients over a 2.5 year period and define six clinical trajectory groups (TGs) associated with demographics, diagnoses, vitals, labs, imaging, consultations, and medications.

We show that the proportion of mild patients increased over time, particularly during Omicron waves. Additionally, while mild and fatal patients had differences in age, age did not distinguish patients with severe versus critical disease. Furthermore, we find that both male sex and Hispanic/Latino ethnicity are associated with more severe/critical TGs. More severe patients also have a higher rate of neuropsychiatric diagnoses and consultations, along with an immunological signature of high neutrophils and immature granulocytes, and low lymphocytes and monocytes. Interestingly, low albumin is one of the best lab predictors of COVID-19 severity in association with higher malnutrition in severe/critical patients, raising concern of nutritional insufficiency influencing COVID-19 outcomes. Despite this, only a small fraction of severe/critical patients had nutritional labs checked (e.g. Vitamin D, thiamine, B vitamins) or received vitamin supplementation.

Our findings expand on clinical risk factors in COVID-19, and highlight the interaction between severity, nutritional status, and neuropsychiatric complications in acute care patients to enable identification of patients at risk for severe disease.

The study focuses exclusively on the results of an arterial blood gas report, which reveal a phenomenal contradiction if one follows the physiological and physicochemical approaches as well as the standard base excess determination to interpret an acid-base disturbance. The aim of this article is not to fully describe a clinical case and make a differential diagnosis but to analyze the blood gas report data in detail and present the conclusions that result from the application of the different approaches that exist for the interpretation of acid-base disorders.

The results of an arterial blood gas report of a patient with severe lactic acidosis were cross-examined using the standard base excess method and the physiologic and physiochemical approaches. The causes of the contradiction are discussed with a commentary on the underlying pathophysiology.

The study revealed the presence of a normal anion gap (even after correction for albumin levels), a slightly increased strong ion gap and a moderately decreased standard base excess in a patient with severe lactic acidosis.

This real-life case provides an opportunity to give a brief overview of the current methods for investigating acid-base disturbances in a practical way, emphasizing both the common background and the conceptual differences and similarities.

Acidosis often occurs during clinical complications in newborns and can lead to changes in the mechanisms of arterial tone regulation. However, it is unknown how acidosis affects the activity of Ca2+-activated chloride channels (CaCC) in arteries during early ontogenesis. We hypothesized that their activity may increase during acidosis.

We studied isometric contractions of saphenous arteries isolated from adult and 10-13-day-old rats. Intracellular pH was measured using a fluorescent indicator BCECF-AM simultaneously with recording the contractile activity of the arterial preparation in isometric mode.

Metabolic acidosis with pH = 6.8 caused a significant decrease in the arterial contractile responses of adult and 10-13-day-old rats. The functional contribution of CaCC was absent in the adult rat arteries both at pH = 7.4 and pH = 6.8. However, in 10-13-day-old rat pups, the functional contribution of CaCC was higher at pH = 6.8 compared to pH = 7.4.

Acidosis augments the functional role of CaCC in arteries during early postnatal ontogenesis, but not in adulthood.

Despite availability of preventive vaccine and global control of the SARS-CoV-19 transmission, continuous emergence of new strains coupled with the increase spread of Mpox poses significant public health threats. Identification of simple factors for stratification and prognostics of hospitalized patients is crucial for management of these patients in limited resource settings. The aim of this study was to assess the biological profile of severe hospitalized COVID-19 patients in Cameroon and identify risk factors for mortality.

A prospective, cross-sectional, analytical study was conducted of a cohort of COVID-19 patients admitted and managed at the Adlucem hospital in Banka-Bafang, Haut-Nkam Department, West Cameroon Region, from 2021 to 2022. The clinical characteristics and biological parameters of patients with COVID-19 were evaluated.

Of the 259 cases of COVID-19 included in the study, 68 cases (26.3%) died. The majority of patients who died were over 70 years of age. Key factors predictive of mortality in these patients were leukocytosis (OR = 2.035; 95%CI: 1.161-3.567; p = 0.013), thrombocytosis (OR = 4.286; 95%CI: 1.152-15.950; p = 0.030), hypokalemia (OR = 2.400; 95%CI: 1.143-5.042; p = 0.021), hyponatremia (OR = 2.292; 95%CI: 1.185-4.431; p = 0.014) and hypochloremia (OR = 2.644; 95%CI: 1.188-5.882; p = 0.017).

Age, electrolyte imbalance and thrombocytosis were predictive of death in COVID-19 patients in this cohort. Thus, a biological work-up should be considered for risk stratification to ensure efficient management of COVID-19 patients on a case-by-case basis in resource limited settings like Cameroon.

Not applicable.

The prevalence of metabolic acidosis is high in patients with chronic kidney disease (CKD). For the diagnosis, a blood gas analysis is necessary, but not always available. The aim of the study was to evaluate the base excess (BE) of the sodium-chloride difference (BENa-Cl = Na+-Cl--34 mmol/l) as a screening parameter for hyperchloremic metabolic acidosis.

We retrospectively performed acid-base analyses of 168 non-dialysed patients with CKD according to the physiologic and to the Stewart's approach. We performed linear regression analysis, Bland-Altman plot and receiver operating characteristics (ROC) analysis of BENa-Cl and BE to evaluate the accuracy of BENa-Cl predicting the BE. We further investigated possible confounding factors.

The corrected R2 for the correlation of BENa-Cl and BE was 0.60 (p < 0.001). The Bland-Altman plot showed a good overall agreement. The bias was negligible, but the 95%-limits of agreement showed a wide interval (10.4 mmol/l). For BE ≤ 2 mmol/l, the ROC analysis yielded an AUC of 0.89 and moderate sensitivity (0.75) and specificity (0.86) for the optimal BENa-Cl threshold (≤ 2 mmol/l). Subgroup analysis showed similar results. The main factor for the imprecision of BENa-Cl predicting the BE across all stages of CKD is the variability of the serum anion gap (SAG).

The BENa-Cl is not an adequate parameter for screening of hyperchloremic acidosis because of the high variability of the SAG. Only, if the BENa-Cl is ≤ 5 mmol/l, a hyperchloremic acidosis should be suspected. Therefore, a complete blood gas analysis is necessary for the correct diagnosis of acid-base disorders in patients with chronic kidney disease.

COVID-19 reduces lung functionality causing a decrease of blood oxygen levels (hypoxemia) often related to a decreased cellular oxygenation (hypoxia). Besides lung injury, other factors are implicated in the regulation of oxygen availability such as pH, partial arterial carbon dioxide tension (PaCO2), temperature, and erythrocytic 2,3-bisphosphoglycerate (2,3-BPG) levels, all factors affecting hemoglobin saturation curve. However, few data are currently available regarding the 2,3-BPG modulation in SARS-CoV-2 affected patients at the hospital admission.

Sixty-eight COVID-19 patients were enrolled at hospital admission. The lung involvement was quantified using chest-Computer Tomography (CT) analysed with automatic software (CALIPER). Haemoglobin concentrations, glycemia, and routine analysis were evaluated in the whole blood, while partial arterial oxygen tension (PaO2), PaCO2, pH, and HCO3- were assessed by arterial blood gas analysis. 2,3-BPG levels were assessed by specific immunoenzymatic assays in RBCs.

A higher percentage of interstitial lung disease (ILD) and vascular pulmonary-related structure (VRS) volume on chest-CT quantified with CALIPER had been found in COVID-19 patients with a worse disease outcome (R = 0.4342; and R = 0.3641, respectively). Furthermore, patients with lower PaO2 showed an imbalanced acid-base equilibrium (pH, p = 0.0208; PaCO2, p = 0.0496) and a higher 2,3-BPG levels (p = 0.0221). The 2,3-BPG levels were also lower in patients with metabolic alkalosis (p = 0.0012 vs. no alkalosis; and p = 0.0383 vs. respiratory alkalosis).

Overall, the data reveal a different pattern of activation of blood oxygenation compensatory mechanisms reflecting a different course of the COVID-19 disease specifically focusing on 2,3-BPG modulation.

Many dogmas influence daily clinical practice, and critical care medicine is no exception. We previously highlighted the weak, questionable, and often contrary evidence base underpinning four established medical managements-loop diuretics for acute heart failure, routine use of heparin thromboprophylaxis, rate of sodium correction for hyponatremia, and 'every hour counts' for treating bacterial meningitis. We now provide four further examples in this "Dogma II" piece (a week's course of antibiotics, diabetic ketoacidosis algorithms, sodium bicarbonate to improve ventricular contractility during severe metabolic acidosis, and phosphate replacement for hypophosphatemia) where routine practice warrants re-appraisal.

Systemic stress, inflammation, and hydroelectrolytic and acid‒base abnormalities observed during diabetic ketoacidosis (DKA) can cause changes in the heart and even induce cardiovascular damage. We aimed to evaluate the structure and function of the heart during and after a DKA episode via echocardiography and biomarker assessment.

We performed a transthoracic echocardiogram (TTE) in subjects with an episode of DKA in the first 4-6 h of treatment. We evaluated left ventricular wall thickness, diameters and volumes, as well as systolic and diastolic function using tissue Doppler imaging, pulsed wave Doppler and left ventricular ejection fraction (LVEF). Left ventricular function was also assessed with global longitudinal strain (GLS). We obtained cardiac troponin levels in the first 24 h after admission. A second TTE was performed following the same protocol 6-12 h after the resolution of the DKA episode.

We included a total of 20 subjects. The mean age was 33 ± 13.6 years; 70% were female, and 70% had type 1 DM. 75% of the patients experienced severe episodes, and the rest experienced moderate episodes. Left ventricular isovolumetric contraction and ejection time were significantly shorter during DKA and prolonged after the resolution of the episodes (47.6 ± 9.9 vs. 62.2 ± 14.1, p = < 0.001) and (218.6 ± 37.9 vs. 265.06 ± 34.7). The isovolumetric relaxation time was also shorter during DKA, (41.72 ± 8.29 vs. 59.32 ± 17.98, p = < 0.001). Volumes and diameters of the left ventricle increased significantly after DKA resolution. We found no difference between LVEF or GLS during and after DKA resolution. 20% of the participants had troponin elevations, half of whom had moderate episodes and half of whom had severe episodes. 35% had LV dysfunction, 28.5% both in GLS and LVEF. 28.5% occurred after DKA resolution, with alterations in GLS.

Diabetic ketoacidosis induces changes in the structure and function of the heart, which are mostly transient, reflect the presence of a hyperdynamic state and resolve after the resolution of the episode. Some subjects present with evidence of myocardial injury with elevated cardiac troponin and left ventricular dysfunction.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can result in severe respiratory acidosis. Metabolic compensation is primarily achieved by renal retention of bicarbonate. The extent to which acute kidney injury (AKI) impairs the kidney's capacity to compensate for respiratory acidosis remains unclear.

This retrospective analysis covers clinical data between January 2009 and December 2021 for 498 ICU patients with AECOPD and need for respiratory support.

278 patients (55.8%) presented with or developed AKI. Patients with AKI exhibited higher 30-day-mortality rates (14.5% vs. 4.5% p = 0.001), longer duration of mechanical ventilation (median 90 h vs. 14 h; p = 0.001) and more severe hypercapnic acidosis (pH 7.23 vs. 7.28; pCO2 68.5 mmHg vs. 61.8 mmHg). Patients with higher AKI stages exhibited lower HCO3-/pCO2 ratios and did not reach expected HCO3- levels. In a mixed model analysis with random intercept per patient we analyzed the association of pCO2 (independent) and HCO3- (dependent variable). Lower estimates for averaged change in HCO3- were observed in patients with more severe AKI.

AKI leads to poor outcomes and compromises metabolic compensation of respiratory acidosis in ICU patients with AECOPD. While buffering agents may aid compensation for severe AKI, their use should be approached with caution.

Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) is utilized to minimize hemodilution. However, removing high volumes leads to tissue hypoperfusion by activating the anaerobic glycolysis pathways. This study aimed to determine the association between weight-indexed CUF volumes and lactate in patients who underwent coronary artery bypass grafting (CABG).

In this single-center retrospective study, 641 CABG patients, who were referred to Al-Zahra Hospital (Shiraz, Iran) and underwent CPB, during 2019-2021, were recruited. Peri-operative parameters were extracted from the patient's records. The patients with non-elective status, pre-existing liver and renal diseases, ejection fraction<35%, and repeated sternotomy were excluded from the study. An increase in post-operative lactate level≥4 mmol/L after 6 hours was defined as hyperlactatemia (HL). To predict HL, univariable and multiple logistic regression modeling, while controlling confounding factors, were employed.

The patients' mean age was 58.8±11.1 years, and 39.2% were women. The incidence of HL was 14.5% (93 patients). There was a significant association between weight-indexed CUF volume and HL. The volume removed in the HL patients was almost doubled (43.37±11.32 vs. 21.41±8.15 mL/Kg, P<0.001), and the higher the weight-indexed CUF volume, the more likely to develop an HL at a rate of 1.38 (Odds ratio=1.38 [1.27-1.49], 95% CI, P<0.001). Furthermore, the multiple logistic regression model showed that HL was associated with the lowest mean arterial pressure (MAP) during CPB.

A higher volume of ultrafiltration was associated with increased post-operative serum lactate levels.

Continuous renal replacement therapy (CRRT) is the most frequently used modality of renal replacement therapy (RRT) in critical care patients with acute kidney injury (AKI). Adequate CRRT delivery can be challenging, due to problems with circuit patency. To improve circuit patency, we developed a new CRRT protocol using continuous veno-venous hemodiafiltration (CVVHDF) with 3.0 mmol/l regional citrate anticoagulation (CVVHDF/RCA3.0) as our first choice RRT modality.

Retrospective comparison of efficacy and safety of a CVVHDF/RCA3.0 protocol with our former continuous veno-venous hemofiltration protocol with 2.2 regional citrate anticoagulation (CVVH/RCA2.2) in adult critically ill patients with AKI requiring CRRT between 25 April 2020 and 24 October 2021.

In total, 56 patients (257 circuits) and 66 patients (290 circuits) were included in the CVVH/RCA2.2 and CVVHDF/RCA3.0 groups, respectively. Median circuit survival was significantly higher in patients treated with CVVHDF/RCA3.0 (39.6 (IQR 19.5-67.3) hours) compared to patients treated with CVVH/RCA2.2 (22.9 (IQR 11.3-48.6) hours) (P < .001). Higher body weight and higher convective flow were associated with a lower circuit survival. Metabolic control was similar, except for metabolic alkalosis that occurred less frequently during CVVHDF/RCA3.0 (19% of patients) compared to CVVH/RCA2.2 (46% of patients) (P = .006).

CRRT circuit survival was longer with CVVHDF/RCA3.0 compared to CVVH/RCA2.2. CRRT circuit survival was negatively associated with higher body weight and higher convective flow.

Cerebrovascular autoregulation (CA) capacity can be impaired in the aftermath of acute brain injuries. Altered physiological states, such as hypo- and hypercapnia, affect CA. Although these effects have been demonstrated in several animal experiments, the exact effect of PaCO₂ on the plateau of cerebral blood flow (CBF) across the spectrum of arterial blood pressures has not been fully disclosed.

The aim was to explore pial vasodynamics in response to changing PaCO₂ in a porcine cranial window model, as preparation for an experimental setup in which the CBF plateau position is investigated under different PaCO₂ conditions.

Five piglets were brought under anesthesia, intubated, ventilated and instrumented with a cranial window through which pial arteriolar diameters could be microscopically observed. By changing ventilation to either hyper- or hypoventilation we were able to investigate a range of PaCO2 from 25 till 90 mmHg.

Altering the respiratory rate to manipulate PaCO₂ by ventilation appeared to be feasible and reliable.

We found that ETCO₂ reliably represents PaCO₂ in our model. Pial arteriolar diameter changes followed the direction of PaCO₂ changes, but the effect of PaCO₂ on the diameters was not linear. Only in the hypercapnia setting did we observe a clear and consistent vasodilation of the pial arterioles.

Few studies have investigated the relationship between the anion gap, including the corrected anion gap, and patient mortality in intensive care units (ICUs) without restricting the analysis to specific diseases or medical specialties. Our primary objective was to investigate the association between the anion gap and ICU mortality using multiple open-access databases.

We identified 4229 subjects from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, whose entries were from between 2008 and 2019. For each patient, the anion gap and corrected anion gap were calculated, and the study sample was divided into tertile groups (T) according to these levels. The association between the anion gap and in-hospital mortality was assessed using hazard ratios (HRs) and 95% confidence intervals (CIs) derived from a multivariable-adjusted Cox proportional hazards model. Besides MIMIC-IV, we also incorporated study samples from two other databases (MIMIC-III and electronic ICU) to calculate summary HRs using a random-effects meta-analysis.

Within MIMIC-IV, 1015 patients (24%) died during an average follow-up period of 15.5 days. The fully adjusted HRs and 95% CIs for T2 and T3, relative to T1, were 1.31 (95% CI 1.08-1.58) and 1.54 (95% CI 1.24-1.90), respectively. When grouped by corrected anion gap, the results remained statistically significant. In the meta-analysis, the summary HRs and 95% CIs for T2 and T3 were 1.24 (95% CI 1.08-1.43) and 1.55 (95% CI 1.33-1.82), respectively.

Both the anion gap and corrected anion gap were associated with in-hospital mortality regardless of specific diseases or medical specialties.

The objective of this review is to discuss acid-base physiology, describe the essential steps for interpreting an arterial blood gas and relevant laboratory tests, and review the 4 distinct types of acid-base disorders.

A comprehensive literature search and resultant bibliography review of PubMed from inception through March 7, 2023.

Relevant English-language articles were extracted and evaluated.

Critically ill patients are prone to significant acid-base disorders that can adversely affect clinical outcomes. Assessing these acid-base abnormalities can be complex because of dynamic aberrations in plasma proteins, electrolytes, extracellular volume, concomitant therapies, and use of mechanical ventilation. This article provides a systematic approach to acid-base abnormalities which is necessary to facilitate prompt identification of acid-base disturbances and prevent untoward morbidity and mortality.

Many acid-base disorders result from medication therapy or are treated with medications. Pharmacists are uniquely poised as the medication experts on the multidisciplinary team to assist with acid-base assessments in the context of pharmacotherapy.

The use of a systematic approach to address acid-base disorders can be performed by all pharmacists to improve pharmacotherapy and optimize patient outcomes.

New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections.

We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with Pseudomonas aeruginosa by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression.

In a rabbit model of non-ventilated pneumonia, endobronchial challenge with live P. aeruginosa strain 6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO2 <60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (P<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved Cmax/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had Cmax/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects.

The rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated P. aeruginosa pneumonia.

Background Heparin anticoagulation (HA) is commonly employed for membrane therapeutic plasma exchange (mTPE). However, for patients with increased bleeding risk, there were controversial opinions on the use of HA versus regional citrate anticoagulation (RCA) for mTPE. Our present study aimed to evaluate the efficacy and safety of HA vs. RCA for mTPE in patients with increased bleeding risk.Methods Patients with increased bleeding risk who underwent mTPE between 2014 and 2021 in our center were screened. Observations of anticoagulation efficacy and safety were used as the study endpoints.Results A total of 108 patients with 368 mTPE sessions were included. Of the included patients, 38 and 70 received HA and RCA mTPE, respectively. There was no significant difference in the clotting of extracorporeal circuits between the HA and RCA groups (4.1% vs. 4.4%, p = 0.605). More bleeding episodes were observed in the HA group compared to the RCA group (16.4% vs. 4.4% mTPE sessions, p < 0.001). The frequency of postoperative transfusion within 24 h (11% vs. 3.4%, p = 0.007) was significantly different in the HA and RCA group. Anticoagulation strategy (HA vs. RCA; OR 5.659, 95%CI 2.266-14.129; p < 0.001), and mean arterial pressure (prior treatment, OR 1.052, 95%CI 1.019-1.086; p = 0.002) were independent risk factors of bleeding episodes. At the end of mTPE treatment, the incidence of metabolic alkalosis (16.7% vs. 54.1%, p = 0.027) and hypocalcemia (41.7% vs. 89.2%, p = 0.001) was significantly different in the HA (n = 5, 12 sessions) and RCA (n = 22, 74 sessions) groups, respectively.Conclusion RCA is as effective as HA for mTPE. However, for patients with increased bleeding risk, RCA is associated with a lower risk of bleeding, compared with HA. With careful monitoring and timely adjustment, RCA most likely is a safe and effective anticoagulation option for mTPE in patients with increased bleeding risk.

This study aims to assess the impact of different subtypes of extreme acidosis on the mortality of critically ill patients.

This retrospective cohort study included critically ill patients who were admitted to the intensive care unit (ICU) with a pH level <7. Clinical data and blood gas analyses were collected from electronic medical records. The primary outcome was in-hospital mortality. The use of vasopressors, mechanical ventilation (MV), and renal replacement therapy (RRT), the duration of MV and RRT, and the length of ICU and hospital stay were secondary outcomes. The simplified Stewart approach to acid-base disorders was used to analyze the causes of acidosis.

A total of 231 patients with 371 arterial blood gas analyses with pH < 7 were admitted from January 2012 to December 2021 and 222 were included in the study. Out of the 222 patients analyzed, respiratory acidosis was the primary disorder in 11.3% of patients (n = 25), metabolic acidosis in 33.8% (n = 75), and mixed acidosis in 55% (n = 122). Overall mortality was 42.8% (n = 95). No significant difference was observed in mortality among patients with respiratory, metabolic, or mixed acidosis (28%, 42.7%, and 45.9%, respectively; p = 0.26). The primary disorder affected the use of vasopressors and MV, the duration of MV, and the length of ICU and hospital stay. Patients with extreme acidosis due to unmeasured anions with lactate levels of 4 mmol/L or higher had higher mortality compared with patients with lactate levels <4 mmol/L (55.6% and 27.7%, respectively; p = 0.007).

Among critically ill patients with extreme acidosis, the primary disorder is not associated with mortality, but it is associated with the use of vasopressors and MV, the duration of MV, and the length of ICU and hospital stay. Additionally, hyperlactatemia is a predictor of poor prognosis in patients with extreme acidosis.

We report an infant case of transient distal renal tubular acidosis and Fanconi syndrome caused by rotavirus gastroenteritis. A 10-month-old boy was admitted to the hospital because of frequent vomiting, lack of vitality, and dehydration. He was diagnosed with rotavirus gastroenteritis on account of his positive stool rotavirus antigen test. Although he presented with acidemia and severe mixed metabolic acidosis, he also had a urine pH of 6.0, indicating impaired urinary acidification. Therefore, he was diagnosed with distal renal tubular acidosis. On the third day of hospitalization, a relatively low %tubular reabsorption of phosphate level with hypophosphatemia, increased fractional excretion of uric acid with hypouricemia, and high urinary β2-microglobulin levels were observed. Moreover, he was diagnosed with Fanconi syndrome on account of multiple proximal tubular dysfunctions. After remission of rotavirus gastroenteritis, the signs of renal tubular dysfunction improved. This was a case of rotavirus gastroenteritis-caused transient distal renal tubular acidosis and Fanconi syndrome. Severe metabolic acidosis resulted from anion-gap metabolic acidosis due to acute kidney injury by rotavirus gastroenteritis and normal anion-gap acidosis due to renal tubular acidosis. When renal tubular acidosis is associated with a disease that causes anion-gap metabolic acidosis, mixed metabolic acidosis occurs and becomes exacerbated. Furthermore, it is important to consider the complications of renal tubular acidosis in the case of severe metabolic acidosis.

Metabolic acid-base disturbances are frequently encountered in the emergency department, and many of these patients are critically ill. In the evaluation of patients with these maladies, it is important for the emergency clinician to determine the cause, which can usually be elicited from a thorough history and physical examination. There are several mnemonics that can be used to form an appropriate list of potential causes. Most of the time, the management of these patients requires no specific treatment of the acid-base status but, rather, requires treatment of the underlying disorder that is causing the acid-base disturbance.

Metformin intoxication causes lactic acidosis by inhibiting Krebs' cycle and oxidative phosphorylation. Continuous renal replacement therapy (CRRT) is recommended for metformin removal in critically ill patients. According to current guidelines, regional citrate anticoagulation (RCA) is the first-line strategy. However, since metformin also inhibits citrate metabolism, a risk of citrate accumulation could be hypothesized. In the present study, we monitored the potential citrate accumulation in metformin-associated lactic acidosis (MALA) patients treated with CRRT and RCA using the physical-chemical approach to acid-base interpretation.

We collected a case series of 3 patients with MALA. Patients were treated with continuous venovenous hemofiltration (CVVH), and RCA was performed with diluted citrate solution. Citrate accumulation was monitored through two methods: the ratio between total and ionized plasma calcium concentrations (T/I calcium ratio) above 2.5 and the strong ion gap (SIG) to identify an increased concentration of unmeasured anions. Lastly, a mathematical model was developed to estimate the expected citrate accumulation during CVVH and RCA.

All 3 patients showed a resolution of MALA after the treatment with CVVH. The T/I calcium ratio was consistently below 2.5, and SIG decreased, reaching values lower than 6 mEq/L after 48 h of CVVH treatment. According to the mathematical model, the estimated SIG without citrate metabolism should have been around 21 mEq/L due to citrate accumulation.

In our clinical management, no signs of citrate accumulation were recorded in MALA patients during treatment with CVVH and RCA. Our data support the safe use of diluted citrate to perform RCA during metformin intoxication.

The effectiveness of standard treatment for diabetic ketoacidosis (DKA) in "euglycemic DKA" (EuDKA, blood glucose (BG) ≤ 250 mg/dL) was evaluated with respect to the time to correction of BG ≤ 200 mg/dL, anion gap (AG)≤12 mmol/L, and serum bicarbonate [HCO3] ≥18 mmol/L.

Data were retrieved from an electronic health record (EPIC) for "diabetic ketoacidosis." Patients were categorized by initial BG as EuDKA, middle range DKA (MrDKA, >250 < 600 mg/dL) and hyperosmolar DKA (HyperDKA ≥600 mg/dL).

There were 56 patients (27men, 29women; age 45.8 ± 15.6 (SD) years. The initial 8-h insulin infusion rate (0.05 ± 0.02, 0.09 ± 0.03, 0.14 ± 0.05units/kg/h, p < 0.001) and the time to correction of BG (3.4 ± 1.9, 6.1 ± 2.9 and 9.6 ± 3.9 h, p < 0.001), differed for EuDKA, MrDKA and HyperDKA. There were no differences in the time to correction of AG or [HCO3]. The earlier time to correction of BG in EuDKA resulted in paradoxical longer lag times for correction of [HCO3] (p = 0.003) and AG (p = 0.048). Changes in BG, AG and [HCO3] correlated with insulin infusion rates of 0.08-0.1units/kg/h whereas in EuDKA the insulin infusion rate was 0.05 ± 0.02 units/kg/h.

In EuDKA, correlation analyses suggest that higher glucose and insulin infusion rates than what would be projected for the level of blood glucose are required to reverse ketoacidosis. Prospective trials are required to optimize the levels of glucose and insulin infusions in EuDKA.

Bloch, Konrad E., Talant M. Sooronbaev, Silvia Ulrich, Mona Lichtblau, and Michael Furian. Clinician's corner: counseling patients with chronic obstructive pulmonary disease traveling to high altitude. High Alt Med Biol. 24:158-166, 2023.-Mountain travel is increasingly popular also among patients with chronic obstructive pulmonary disease (COPD), a highly prevalent condition often associated with cardiovascular and systemic manifestations. Recent studies have shown that nonhypercapnic and only mildly hypoxemic lowlanders with moderate to severe airflow obstruction owing to COPD experience dyspnea, exercise limitation, and sleep disturbances when traveling up to 3,100 m. Altitude-related adverse health effects (ARAHE) in patients with COPD include severe hypoxemia, which may be asymptomatic but expose patients to the risk of excessive systemic and pulmonary hypertension, cardiac arrhythmia, and even myocardial or cerebral ischemia. In addition, hypobaric hypoxia may impair postural control, psycho-motor, and cognitive performance in patients with COPD during altitude sojourns. Randomized, placebo-controlled trials have shown that preventive treatment with oxygen at night or with acetazolamide reduces the risk of ARAHE in patients with COPD while preventive dexamethasone treatment improves oxygenation and altitude-induced excessive sleep apnea, and lowers systemic and pulmonary artery pressure. This clinical review provides suggestions for pretravel assessment and preparations and measures during travel that may reduce the risk of ARAHE and contribute to pleasant mountain journeys of patients with COPD.

Severe coronavirus disease 2019 (COVID-19) infection can lead to extensive lung infiltrate, a significant increase in the respiratory rate, and respiratory failure, which can affect the acid-base balance. No research in the Middle East has previously examined acid-base imbalance in COVID-19 patients. The present study aimed to describe the acid-base imbalance in hospitalized COVID-19 patients, determine its causes, and assess its impact on mortality in a Jordanian hospital. The study divided patients into 11 groups based on arterial blood gas data. Patients in normal group were defined as having a pH of 7.35-7.45, PaCO2 of 35-45 mmHg, and HCO3- of 21-27 mEq/L. Other patients were divided into 10 additional groups: mixed acidosis and alkalosis, respiratory and metabolic acidosis with or without compensation, and respiratory and metabolic alkalosis with or without compensation. This is the first study to categorize patients in this way. The results showed that acid-base imbalance was a significant risk factor for mortality (P<0.0001). Mixed acidosis nearly quadruples the risk of death when compared with those with normal levels (OR = 3.61, P=0.05). Furthermore, the risk of death was twice as high (OR = 2) for metabolic acidosis with respiratory compensation (P=0.002), respiratory alkalosis with metabolic compensation (P=0.002), or respiratory acidosis with no compensation (P=0.002). In conclusion, acid-base abnormalities, particularly mixed metabolic and respiratory acidosis, were associated with increased mortality in hospitalized COVID-19 patients. Clinicians should be aware of the significance of these abnormalities and address their underlying causes.

Diabetic ketoacidosis (DKA) is commonly complicated by mixed acid-base disorders. Therefore, patients with DKA can present with pH > 7.3 or bicarbonate > 18 mmol/L, which falls outside the values defined by the current traditional DKA criteria (pH ≤ 7.3 or bicarbonate ≤ 18 mmol/L).

We aimed to study the spectrum of acid-base clinical presentations of DKA and the prevalence of diabetic ketoalkalosis.

This study included all adult patients at a single institution admitted in 2018-2020 with diabetes, positive beta-hydroxybutyric acid, and increased anion gap ≥ 16 mmol/L. Mixed acid-base disorders were analyzed to determine the spectrum of presentation of DKA.

There were 259 encounters identified under the inclusion criteria. Acid-base analysis was available in 227 cases. Traditional acidemic DKA (pH ≤ 7.3), DKA with mild acidemia (7.3 < pH ≤ 7.4), and diabetic ketoalkalosis (pH > 7.4) account for 48.9% (111/227), 27.8% (63/227), and 23.3% (53/227) of cases, respectively. Of the 53 cases with diabetic ketoalkalosis, increased anion gap metabolic acidosis was present in all, and concurrent metabolic alkalosis, respiratory alkalosis, and respiratory acidosis were present in 47.2% (25/53), 81.1% (43/53), and 11.3% (6/53) encounters, respectively. In addition, 34.0% (18/53) of those with diabetic ketoalkalosis were found to have severe ketoacidosis, defined by beta-hydroxybutyric acid ≥ 3 mmol/L.

DKA can present as traditional acidemic DKA, DKA with mild acidemia, and diabetic ketoalkalosis. Diabetic ketoalkalosis is a common yet easily overlooked alkalemic variant of DKA associated with mixed acid-base disorders, and a high proportion of these presentations have severe ketoacidosis and thus, require the same treatment as traditional DKA.

Intraoperative fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy plays an important role in postoperative morbidity. Studies have found an association between overload fluid therapy and increased postoperative complications, advising restrictive intraoperative fluid therapy. Our objective in this study was to compare the morbidity associated with restrictive versus non-restrictive intraoperative fluid therapy.

Retrospective analysis of a database collected prospectively in the Anesthesiology Service of Virgen del Roc.ío Hospital, from December 2016 to April 2019. One hundred and six patients who underwent complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were divided into two cohorts according to Fluid Therapy received 1. Restrictive.ß..±.ß9.ßmL.kg-1.h-1 (34 patients), 2. Non-restrictive .ß.ß....ß9.ßmL.kg-1.h-1 (72 patients). Percentage of major complications (Clavien-Dindo grade III...IV) and length hospital stay were the main outcomes variables.

Of the 106 enrolled patients, 68.9% were women; 46.2% had ovarian cancer, 35.84% colorectal cancer, and 7.5% peritoneal cancer. The average fluid administration rate was 11.ß...ß3.58.ßmL.kg-1.h-1. The restrictive group suffered a significantly higher percentage of Clavien-Dindo grade III...IV complications (35.29%) compared with the non-restrictive group (15.27%) (p.ß=.ß0.02). The relative risk associated with restrictive therapy was 1.968 (95% confidence interval: 1.158...3.346). We also found a significant difference for hospital length of stay, 20.91 days in the restrictive group vs 16.19 days in the non-restrictive group (p.ß=.ß0.038).

Intraoperative fluid therapy restriction below 9.ßmL.kg-1.h-1 in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was associated with a higher percentage of major postoperative complications.

The carbon dioxide/bicarbonate (CO₂/HCO₃^-) molecular pair is ubiquitous in mammalian cells and tissues, mainly as a result of oxidative decarboxylation reactions that occur during intermediary metabolism. CO₂ is in rapid equilibrium with HCO₃^-via the hydration reaction catalyzed by carbonic anhydrases. Far from being an inert compound in redox biology, CO₂ enhances or redirects the reactivity of peroxides, modulating the velocity, extent, and type of one- and two-electron oxidation reactions mediated by hydrogen peroxide (H₂O₂) and peroxynitrite (ONOO^-/ONOOH). Herein, we review the biochemical mechanisms by which CO₂ engages in peroxide-dependent reactions, free radical production, redox signaling, and oxidative damage. First, we cover the metabolic formation of CO₂ and its connection to peroxide formation and decomposition. Next, the reaction mechanisms, kinetics, and processes by which the CO₂/peroxide interplay modulates mammalian cell redox biology are scrutinized in-depth. Importantly, CO₂ also regulates gene expression related to redox and nitric oxide metabolism and as such influences oxidative and inflammatory processes. Accumulated biochemical evidence in vitro, in cellula, and in vivo unambiguously show that the CO₂ and peroxide metabolic pathways are intertwined and together participate in key redox events in mammalian cells.

Elevated lactate levels are a sign of critical illness and may result from insufficient oxygen delivery. We investigated whether hypoxemia and/or systemic inflammation, results in increased lactate levels in healthy volunteers.

30 healthy volunteers were exposed to either 3.5 h of hypoxemia (FiO₂ ± 11.5%), normoxemic endotoxemia (FiO₂ 21%, administration of 2 ng/kg endotoxin), or hypoxemic endotoxemia (n = 10 per group). Blood lactate, hemoglobin, SpO₂, PaO_2, PaCO₂, pH, and hemodynamic parameters were serially measured.

Hypoxemic treatment resulted in lower SpO₂ (81.7 ± 2.6 and 81.4 ± 2.4% in the hypoxemia and hypoxemic endotoxemia groups, respectively) and hyperventilation with a PaCO₂ decrease of 0.8 ± 0.5 and 1.5 ± 0.6 kPa and an increase in pH. Arterial oxygen content (CaO₂) decreased by 20.5 ± 2.9 and 23.5 ± 4.4%, respectively. Lactate levels were slightly, but significantly higher in both hypoxemic groups compared with the normoxemic endotoxemia group over time (p < 0.0001 for both groups), but remained below 2.3 mmol/L in all subjects. Whereas PaO₂ and SpO₂ did not correlate with lactate levels, PaCO₂, pH and CaO₂ did.

Hypoxemia, in the absence or presence of inflammation does not result in relevant increases of lactate. The small increases in lactate observed are likely to be due to hyperventilation-related decreases in glycolysis.

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.

Acidosis decreases myocardial contractile and myofibrillar responsiveness by reducing the calcium sensitivity of contractile proteins, which could reduce the effectiveness of pimobendan. We aimed to assess the cardiovascular effects of pimobendan in dogs subjected to acute respiratory acidosis.

Randomized crossover study with a 2-week washout period.

University Laboratory.

Six healthy research Beagle dogs.

Anesthetized dogs were administered 2 doses of IV pimobendan during conditions of eucapnia (Paco2 35-40 mm Hg) and hypercapnia (Paco2 90-110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO2 to the anesthesia circuit. Heart rate (HR), systemic arterial blood pressure, cardiac output (CO), systemic and pulmonary vascular resistance (SVR and PVR, respectively), and pulmonary arterial pressure (PAP) were measured at baseline and 60 min after administering 0.125 mg/kg (low) and 0.25 mg/kg (high) pimobendan intravenously. Blood gas and biochemical analyses were performed at baseline and at the end of the experiment.

The median baseline blood pH was 7.41 (range: 7.33-7.45) and 7.03 (range: 6.98-7.09) under conditions of eucapnia and hypercapnia, respectively. The serum concentrations of epinephrine and norepinephrine and the HR, CO, and PAP were higher, and SVR was lower at baseline in hypercapnic dogs. Pimobendan dose-dependently increased CO in eucapnia (baseline: 3.6 ± 0.2 L/kg/m2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m2 , high: 5.8 ± 0.5 L/kg/m2 , P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m2 , low: 5.8 ± 0.5 L/kg/m2 , high: 6.2 ± 0.5 L/kg/m2 , P < 0.001), and increased HR and decreased SVR and PVR under both conditions (P < 0.001). In hypercapnia, the degree of increase or decrease of these cardiovascular measurements (except for PAP) by pimobendan was less than that in the eucapnic dogs.

Pimobendan maintains function as an inodilator in anesthetized dogs with induced respiratory acidosis.

Acute heart failure (AHF) may be associated with low-tissue perfusion and/or hypoxaemia leading to increased lactate levels and acid-base perturbations. Few data are available on the clinical significance of elevated lactate levels and primary acid-base disorders in the setting of AHF.

Arterial blood gas was obtained at admission in 4012 normotensive (systolic blood pressure ≥ 90 mmHg) patients with AHF. The association between lactate levels and acid-base status and in-hospital mortality was determined using multivariable logistic regression. Hyperlactataemia (>2 mmol/L) was present in 38.0% of patients and was strongly associated with markers of sympathetic activation, such as hyperglycaemia. Hyperlactataemia was present in 31.0%, 43.7%, and 42.0% of patients with normal pH, acidosis, and alkalosis, respectively. In-hospital mortality occurred in 16.4% and 11.1% of patients with and without hyperlactataemia [adjusted odds ratio (OR) 1.49; 95% confidence interval (CI) 1.22-1.82, P < 0.0001]. Compared with normal pH, the OR for in-hospital mortality was 2.48 (95% CI 1.95-3.16, P < 0.0001) in patients with acidosis and 1.77 (95% CI 1.32-2.26, P < 0.0001) in patients with alkalosis. The risk for in-hospital mortality was high with acidosis (18.1%) or alkalosis (10.4%) even with normal lactate. The most common primary acid-base disturbances included metabolic acidosis, respiratory acidosis, and metabolic alkalosis with respiratory acidosis having the highest risk for in-hospital mortality.

Hyperlactataemia was common in patients without hypotension and was associated with increased risk for in-hospital mortality. Hyperlactataemia is not associated with any specific acid-base disorder. Acute heart failure patients also present with diverse acid-base disorders portending increased in-hospital mortality.