Retrospective Cohort Study Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jun 25, 2024; 13(2): 92498
Published online Jun 25, 2024. doi: 10.5527/wjn.v13.i2.92498
Physico-chemical characterization of acid base disorders in patients with COVID-19: A cohort study
Sergio Pinto de Souza, Marcelo Barreto Lopes, Marcelo Augusto Duarte Silveira, Fernanda Oliveira Coelho, Department of Nephrology, Hospital São Rafael, Salvador, BA 41253190, Brazil
Sergio Pinto de Souza, Marcelo Barreto Lopes, Marcelo Augusto Duarte Silveira, Fernanda Oliveira Coelho, Department of Nephrology, D’Or Institute for Research and Education (IDOR), Salvador, BA 41253190, Brazil
Sergio Pinto de Souza, Faculty of Medicine, Escola Bahiana de Medicina e Saúde Pública-EBMSP, Salvador, BA 40290000, Brazil
Juliana R Caldas, Department of Intensive Care, D’Or Institute for Research and Education (IDOR), Salvador, BA 41253190, Brazil
Igor Oliveira Queiroz, Pedro Domingues Cury, Hospital São Rafael, D’Or Institute for Research and Education (IDOR), Salvador, BA 41253190, Brazil
Rogério da Hora Passos, Department of Intensive Care Unit, Hospital Israelita Albert Einstein, Sao Paulo, SP 05652900, Brazil
ORCID number: Sergio Pinto de Souza (0000-0003-2483-159X); Igor Oliveira Queiroz (0009-0003-9130-1713); Pedro Domingues Cury (0000-0002-5247-6348).
Author contributions: de Souza SP, Caldas JR, Passos RDH, Coelho FO, and Silveira MAD designed the research study; de Souza SP, Silveira MAD, Coelho FO, Queiroz IO, and Cury PD performed the research; de Souza SP, Caldas JR, and Lopes MB provided statistical planning and analysis; de Souza SP, Caldas JR, Queiroz IO, Cury PD, and Lopes MB analyzed the data; de Souza SP, Queiroz IO, Cury PD, and Passos RDH wrote the manuscript; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Review Board (CAAE 34428920.0.0000.0048).
Informed consent statement: A waiver of informed consent was granted by the Ethics Committee.
Conflict-of-interest statement: All the authors declare that they have no conflicts of interest related to the manuscript.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at sergio.pdesouza@hsr.com.br.
STROBE statement: The authors have read the STROBE statement-checklist of items, and the manuscript was prepared and revised according to the STROBE statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sergio Pinto de Souza, Doctor, Associate Professor, Attending Doctor, Department of Nephrology, Hospital São Rafael, Av. São Rafael 2152, Salvador, BA 41253190, Brazil. souzasp@gmail.com
Received: January 27, 2024
Revised: May 8, 2024
Accepted: May 22, 2024
Published online: June 25, 2024
Processing time: 149 Days and 10 Hours

Abstract
BACKGROUND

Acid-base imbalance has been poorly described in patients with coronavirus disease 2019 (COVID-19). Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution that may have been overlooked using traditional acid-base analysis techniques. In a cohort of critically ill COVID-19 patients, we looked for an association between metabolic acidosis surrogates and worse clinical outcomes, such as mortality, renal dialysis, and length of hospital stay.

AIM

To describe the acid-base disorders of critically ill COVID-19 patients using Stewart’s approach, associating its variables with poor outcomes.

METHODS

This study pertained to a retrospective cohort comprised of adult patients who experienced an intensive care unit stay exceeding 4 days and who were diagnosed with severe acute respiratory syndrome coronavirus 2 infection through a positive polymerase chain reaction analysis of a nasal swab and typical pulmonary involvement observed in chest computed tomography scan. Laboratory and clinical data were obtained from electronic records. Categorical variables were compared using Fisher’s exact test. Continuous data were presented as median and interquartile range. The Mann-Whitney U test was used for comparisons.

RESULTS

In total, 211 patients were analyzed. The mortality rate was 13.7%. Overall, 149 patients (70.6%) presented with alkalosis, 28 patients (13.3%) had acidosis, and the remaining 34 patients (16.2%) had a normal arterial pondus hydrogenii. Of those presenting with acidosis, most had a low apparent strong ion difference (SID) (20 patients, 9.5%). Within the group with alkalosis, 128 patients (61.0%) had respiratory origin. The non-survivors were older, had more comorbidities, and had higher Charlson’s and simplified acute physiology score 3. We did not find severe acid-base imbalance in this population. The analyzed Stewart’s variables (effective SID, apparent SID, and strong ion gap and the effect of albumin, lactate, phosphorus, and chloride) were not different between the groups.

CONCLUSION

Alkalemia is prevalent in COVID-19 patients. Although we did not find an association between acid-base variables and mortality, the use of Stewart’s methodology may provide insights into this severe disease.

Key Words: COVID-19, Physicochemical approach, Acid-base status, Critically ill patients, Acute respiratory syndrome

Core Tip: In this retrospective study, alkalemia was the most prevalent acid-base disturbance in critically ill coronavirus disease 2019 (COVID-19) patients. It was mainly of respiratory origin. The results suggested that there was no association between acid-base disturbances and mortality. However, the physicochemical approach appeared to furnish supplementary information concerning the etiological factors involved in assessing metabolic acid-base imbalances in critically ill patients with COVID-19. Nevertheless, ascertaining their correlation with mortality remains pending.



INTRODUCTION

Acid-base disorders are commonly found in the intensive care unit (ICU)[1]. Maintaining blood homeostasis and pondus hydrogenii (pH) regulation is crucial for normal physiology and cellular metabolism and function. The significance of this regulation is demonstrated by various physiological abnormalities that occur when plasma pH is either too high or too low. The body tightly controls acid balance through the respiratory and renal systems, both of which are essential for maintaining acid-base equilibrium[2].

The identification of severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019 (COVID-19), occurred in December 2019[3]. The pulmonary manifestations of COVID-19 are typically characterized by bilateral ground-glass opacities, with or without consolidations. Extensive pneumonia can be a serious infectious disease, as it impairs the exchange of respiratory gases and alters minute ventilation. Consequently, respiratory-related acid-base imbalances are expected complications in COVID-19 patients[4]. Additionally, acute tubular injury is a common complication of the disease. The pathophysiology of COVID-19 acute tubular injury involves local and systemic inflammatory and immune responses, endothelial injury, activation of coagulation pathways, and the renin-angiotensin system. There is also debate surrounding the possibility of direct viral infection with renal tropism. Therefore, renal involvement in COVID-19 may play a significant role in the development of acid-base disturbances[5].

The incidence and effects of acid-base disorders in COVID-19 patients have not been well studied thus far. Since these disorders serve as markers for underlying pathological conditions that can have severe consequences on multiple organs, it is crucial to accurately describe and assess acid-base disorders[6]. Small differences in correcting for anion gap, variations in analytical methods, and different approaches to diagnosing acid-base imbalances can result in significantly different interpretations and treatment strategies for the same disorder. By utilizing a quantitative acid-base approach, clinicians may be able to account for minor changes in ion distribution that may have been overlooked using traditional acid-base analysis techniques[7].

Given that renal and pulmonary changes are commonly observed in COVID-19 patients, we hypothesized that these changes significantly affect acid-base status but may go unnoticed due to counteracting effects. Thus, the primary objective of this study was to analyze acid-base balance using the physicochemical method of Stewart. The secondary objective was to identify any potential association with outcomes such as dialysis need, vasopressor use, duration of hospital stay, and mortality.

MATERIALS AND METHODS
Population

This was a retrospective study conducted in a tertiary 600-bed hospital in Salvador, northeastern Brazil from March 2020 to December 2020. All adult patients who were more than 18 years of age at their first admission to the ICU at our hospital were screened for eligibility. The inclusion criteria were an ICU stay of more than 4 days, blood gas collection on the same day of ICU admission, a COVID-19 diagnosis by a positive test from a nasal swab, and a typical pulmonary involvement observed in the chest computed tomography scan. We excluded patients with chronic kidney disease stages 4 and 5, patients with acute kidney injury on dialysis, pregnant women, and patients with a kidney transplant. The swab was collected on the ICU admission day, and the viral RNA was detected by quantitative real-time-polymerase chain reaction (qRT-PCR) to confirm severe acute respiratory syndrome coronavirus 2 infection.

All patients were followed until discharge, death, or hospital transference. The study was conducted according to the principles of the Declaration of Helsinki and was approved by the Ethics Committee for Analysis of Research Projects of the Hospital São Rafael, Salvador, Brazil. A waiver of informed consent was granted by the Ethics Committee.

Data extraction and analysis

We obtained demographic (age, sex, simplified acute physiology score 3, sequential organ failure assessment, and Charlson’s comorbidity index scores, hospital mortality), laboratory, radiological, treatment, and clinical outcome data from electronic medical records. Acute kidney injury was diagnosed by the kidney disease: Improving Global Outcomes criteria[8].

At ICU admission, an arterial blood sample was analyzed using a Siemens RAPID Point 500 blood gas analyzer (Siemens Health Care, Erlangen, Germany) to investigate acid-base disorders using both Henderson-Hasselbach and Stewart’s methodologies. From these data, the base deficit, anion gap, apparent strong ion difference (SIDa) and effective SID (SIDe) respectively, and strong ion gap (SIG) were calculated as described previously[9]: (1) Anion gap = (Na+ + K+) - (Cl- + HCO3-); (2) SIDa = (Na+ + K+ + Ca2+ + Mg2+) - (Cl- + lactate-); (3) SIDe = 2.46 × 10-8 × partial pressure of carbon dioxide (PCO2)/10-pH + Albumin × (0.123 x pH - 0.631) + PO42- × (0.39 × pH - 0.469), and (4) SIG = SIDa – SIDe.

According to the physicochemical approach (Stewart’s), we classified acidosis, alkalosis, and no pH disorder based on the partial PCO2 and the electrolyte composition of blood as follows[10]: (1) A pH of less than 7.38 was categorized as acidosis, a pH of more than 7.42 was categorized as alkalosis, and a pH between 7.38 and 7.42, with PCO2 between 38 mmHg-42 mmHg and SIDa between 38 mEq/L-42 mEq/L, was categorized as no disorder; (2) Respiratory acidosis: PH < 7.38, PCO2 > 42 mmHg, and SIDa between 38 mEq/L-42 mEq/L; (3) Metabolic acidosis secondary to SIDa: PH < 7.38, PCO2 between 38 mmHg-42 mmHg, and SIDa < 38 mEq/L; (4) Other metabolic acidosis: PH < 7.38, PCO2 between 38 mmHg-42 mmHg, and SIDa between 38 mEq/L-42 mEq/L; (5) Respiratory alkalosis: PH > 7.42, PCO2 < 38 mmHg, and SIDa 38 mEq/L-42 mEq/L; (6) Metabolic alkalosis secondary to SIDa: PH > 7.42, PCO2 between 38 mmHg-42 mmHg, and SIDa > 42 mEq/L; (7) Other metabolic alkalosis: PH > 7.42, PCO2 between 38 mmHg-42 mmHg, and SIDa between 38 mEq/L-42 mEq/L; and (8) Mixed disorder pH 7.38-7.42 with PCO2 > 42, and SIDa > 42 mEq/L or PCO2 < 38 and SIDa < 38 mEq/L.

Statistical analysis

Categorical variables were compared using Fisher’s exact test. Continuous data were presented as median and interquartile range or mean ± SD, as appropriate. The Mann-Whitney U test or the Student’s t-test was used for comparisons. P < 0.05 were considered significant. Data were analyzed with the PSPP® statistical package, version 1.2.1 (GNU Project, www.gnu.org/software/pspp/).

RESULTS
Clinical data

During the evaluation period, a total of 799 patients had a positive COVID-19 nasal swab by RT-PCR in our hospital, and 456 were admitted to the ICU. Among them, 254 patients had an ICU stay longer than 4 days. Forty-three patients were excluded due to age less than 18 years, advanced chronic kidney disease, and no arterial blood gas analysis at ICU admission.

Demographic, laboratory, and acid-base variables are shown in Table 1. The mean age of the population was 59.7 years ± 17.1 years with a higher predominance of males (60.0%). Overall, the non-survivors were older (79.0 years ± 9.0 years vs 58.6 years ± 16.0 years, P = 0.000) and had more comorbidities such as high blood pressure (74.0% vs 49.0%, P = 0.040), diabetes mellitus (50.0% vs 30.0%, P = 0.050), or chronic pulmonary disease (26.0% vs 12.0%, P = 0.100). We found higher Charlson’s and simplified acute physiology score 3 scores in non-survivors. Secondary infections were diagnosed more frequently in this group of patients (100% vs 46.8%, P = 0.000). Vasoactive drugs, mechanical ventilation, acute kidney injury, and dialysis were associated with mortality. As expected, patients who did not survive had a longer hospital and ICU stay (median of 22.0 days vs 17.0 days and 21.0 days vs 11.0 days, respectively), but a shorter disease duration at hospital admission (8.2 days vs 10.1 days).

Table 1 Clinical and laboratory variables of 211 critically ill coronavirus disease 2019 patients, n (%).
Variable
All patients
Survivors
Non-survivors
P value
Age in years 59.7 ± 17.158.6 ± 16.079.0 ± 9.00.000
Male sex99 (60.0)84 (59.0)15 (65.0)0.650
T2DM55 (33.4)43 (30.0)12 (50.0)0.050
Hypertension87 (53.0)70 (49.0)17 (74.0)0.040
COPD or asthma23 (14.0)17 (12.0)6 (26.0)0.100
SOFA score 2 (1.0-3.0)2 (1.0-3.0)3 (1.5-4.0)0.110
Charlson’s score 3 (1.0-4.0)2 (1.0-4.0)5 (4.0-7.0)0.000
SAPS 342.0 ± 19.042.0 ± 16.461.0 ± 15.00.000
Antimicrobial treatment89 (54.0)66 (46.8)23 (100)0.000
PO2/FIO2296 ± 87308 ± 94264 ± 1160.360
HFO2/NIV83 (50.6)67 (47.5)16 (69.5)0.040
Lung involvement0.360
< 25%13.412.021.7
25%-50%44.546.830.4
50%-75%34.734.734.7
> 75%6.75.613.0
VAD at admission25 (15.0)18 (12.0)7 (30.0)0.050
VAD any time60 (37.0)39 (27.0)21 (91.0)0.000
MV65 (40.0)43 (30.0)22 (95.0)0.000
AKI50 (30.4)28 (19.8)22 (95.6)0.000
KDIGO 118 (11.0)17 (12.0)1 (4.3)0.000
KDIGO 27 (4.2)5 (3.5)2 (8.7)
KDIGO 325 (15.2)6 (4.2)19 (82.6)
Dialysis19 (11.6)2 (1.4)17 (73.0)0.000
Hospital stay in day 13 (10.0-21.0)17 (9.0-20.5)22 (13.0-32.0)0.005
ICU stay in day 12.6 (5-17)11.0 (9-14)21.0 (18-25)0.000
Illness day7.0 (5.0-9.0)10.1 (5.0-8.7)8.2 (3.0-17.0)0.003
Days in hospital0 (0-1)0 (0-1)0 (0-1)0.410
Ferritin (normal range: 12 ng/mL-300 ng/mL)985 ± 14471088 ± 1529679 ± 6090.170
Leukocyte count (normal range: 3.6 × 109/L-11.0 × 109/L)7.0 (5.5-9.1)7.1 (5.1-9.4)6.6 (4.3-8.9)0.720
Lymphocyte count (normal range: 1 × 109/L-4 × 109/L)0.860.920.780.040
Platelet count (normal range: 150 × 109/L-400 × 109/L)179 (151-237)191 (151-244)169 (148-219)0.290
Creatinine (normal range: 0.5 mg/dL-1.3 mg/dL)0.83 (0.67-0.98)0.83 (0.65-0.98)0.84 (0.69-0.99)0.770
D dimer (normal range < 250 ng/mL)832 (563-1740)880 (536-1651)1512 (746-2151)0.040
Fibrinogen (normal range: 200 mg/dL-400 mg/dL)532 ± 185555 ± 206580 ± 1790.580
Total bilirubin (normal range: 0.2 mg/dL-1.2 mg/dL)0.5 (0.4-0.7)0.5 (0.4-0.7)0.6 (0.4-0.7)0.930
Laboratory data

The blood gas and acid-base variables are shown in Table 2. Overall, 149 patients (70.6%) presented with alkalosis, 28 patients (13.3%) had acidosis, and the remaining 34 patients (16.2%) had a normal arterial pH. From those presenting with acidosis, most had a low SIDa (20 patients, 9.5%). Within the group with alkalosis, 128 patients (61% of all patients) had respiratory origin. We found no statistically significant differences in pH, PCO2, bicarbonate, or lactate levels between survivors and non-survivors. Serum sodium and chloride levels were slightly higher in survivors (P < 0.010 and P < 0.030, respectively). We also searched for differences in Stewart’s variables between these two groups. The values of SIDe, SIDa, and SIG and the effect of albumin, lactate, phosphorus, and chloride were not different between the groups.

Table 2 Physicochemical analysis of 211 critically ill coronavirus disease 2019 patients.
Parameter
All patients
Survivors
Non-survivors
P value
PH (normal range: 7.38-7.42)7.46 (7.42-7.53)7.45 (7.40-7.47)7.45 (7.40-7.50)0.850
PCO2 (normal range: 36 mmHg-44 mmHg)34.1 ± 5.634.0 ± 5.734.5 ± 4.80.660
Bicarbonate (normal range: 24 mEq/L ± 2 mEq/L)23.3 (21.0-24.8)23.3 (20.9-24.9)23.1 (21.7-24.4)0.630
Lactate normal range: (4 mg/dL-18 mg/dL)12.1 (2.0-15.9)11.5 (1.9-15.2)13.9 (10.7-21.2)0.130
Albumin (normal range: 4.0 g/dL-5.5 g/dL)3.6 (3.2-3.8)3.6 (3.3-3.8)3.4 (3.2-3.8)0.650
Phosphorus (normal range: 2.5 mg/dL–4.5 mg/dL)3.57 ± 0.843.58 ± 0.863.44 ± 0.680.450
Sodium (normal range: 135 mEq/L-142 mEq/L)135 (133-138)136 (134-138)135 (129-136)0.010
Potassium (normal range: 3.5 mEq/L-5.2 mEq/L)4.17 ± 0.514.17 ± 0.514.15 ± 0.520.820
Chloride (normal range: 96 mEq/L-106 mEq/L)100 (97-103)100 (98-103)98 (94-100)0.030
SIDa37.96 ± 4.3037.81 ± 4.3337.86 ± 4.210.920
SIDe35.35 ± 3.5035.42 ± 3.6434.94 ± 3.150.670
SIG2.69 (-0.30 to 4.94)2.67 (0.21-4.99)2.71 (-0.40 to 4.88)0.930
SBE-0.35 (-2.90 to 1.30)-0.33 (-3.00 to 1.40)-0.84 (-2.30 to 0.28)0.740
Chloride effect-2.44 (-4.80 to 0.28)-2.44 (-5.50 to 0.70)-2.58 (-4.80 to 11.58)0.580
Lactate effect-1.47 (-1.90 to 1.20)-1.45 (-1.86 to 1.20)-1.69 (-2.34 to 1.30)0.240
Albumin effect1.51 (0.60-2.60)1.49 (0.60-2.46)1.82 (0.76-2.73)0.730
Phosphorus effect-0.02 ± 0.500 ± 0.520.10 ± 0.400.270
DISCUSSION

In this cohort of critically ill COVID-19 patients, the quantitative approach to acidosis demonstrated that the main acid-base disorder was alkalosis, with the majority of these being of respiratory origin. The remaining patients had either metabolic acidosis or alkalosis. Among patients with metabolic acidosis, the majority had low SIDa. The results of this study were consistent with other studies that addressed this topic. Alfano et al[6] described metabolic and respiratory alkalosis as the main acid-base disorders, but metabolic alkalosis was the most frequent finding without specification of the etiology. In patients with respiratory failure treated with noninvasive mechanical ventilation, the most frequent acid-base disorder described was alkalosis, also of metabolic or respiratory origin. As an additional finding, the patient’s diagnosis was only possible through the quantitative method in 12% of patients[11]. This innovative methodology seems more suitable for studying the complex acid-base abnormalities in critically ill patients[12]. Some authors argue that this mechanistic approach may resolve several inconsistencies in the traditional model, give rise to novel clinical applications, and enhance understanding of pharmacological manipulation of electrolytes and clinical fluid management[13].

Respiratory alkalosis was the main acidosis-based disorder identified in our population. This disturbance involves an increase in respiratory rate and/or tidal volume. In patients admitted with respiratory failure, this finding has already been correlated with the presence of a greater extent of pulmonary inflammatory involvement identified by chest computed tomography. In this way, it can be a sign of greater severity and the need for a faster decision-making process[14]. Patient self-inflicted lung injury might be one of the many factors that can explain progression of lung disease in COVID-19. Patients who have injured lungs typically experience a heightened respiratory drive due to the impairment of gas exchange and respiratory mechanics. If the neuromuscular transmission is intact, this increased respiratory drive leads to powerful inhalations that may have physiological effects, such as a risk of over-distension, pendelluft, or atelectrauma, and an increase in vascular transmural pressure. Consequently, these effects are likely to worsen the existing lesions. This further deterioration of gas exchange and respiratory mechanics results in an even higher respiratory drive, which then exposes the lungs to the risks of even stronger inspiratory efforts. Therefore, the concept of patient self-inflicted lung injury incorporates a dynamic aspect that functions as a vicious circle[15]. The presence of respiratory alkalosis in these patients can be justified by excessive ventilatory effort and increased breath work. It can be used as a marker of underlying severity and should be approached with a sense of urgency and be judiciously corrected[16].

In our study, the diagnosis and variables involved in the quantitative assessment of acid-base disorders were not associated with mortality and other outcomes. The performance of the quantitative approach for determining the prognosis of critically ill patients has been questioned due to the impact of lactate, other measured ions, and even therapeutic interventions from the Stewart equation[17].

Bezuidenhout et al[18], in a single-center African retrospective observational study, found that most patients admitted to the ICU had alkalosis and a lower partial pressure of oxygen, which was associated with survival. They suggested that alkalosis could be caused by the activation of the traditional branch of the renin-angiotensin system and the resulting rise in the effects of aldosterone.

Aldosterone levels in critically ill patients are abnormally low despite an increase in plasma renin activity. This dissociation of aldosterone is not caused by a decrease in angiotensin II synthesis or alterations in plasma adrenocorticotropic hormone and potassium ions. This phenomenon has been linked to a higher mortality rate during critical illness.

Al-Azzam et al[19] found that mixed metabolic and respiratory acidosis were associated with increased mortality in COVID-19 patients. These findings may have been influenced by the higher prevalence of patients with diabetes mellitus, chronic kidney disease, and severe respiratory failure with hypercapnia in this patient population.

Limits of the study

Our study was designed to investigate the acid-base and electrolyte disturbances in COVID-19 patients with severe pulmonary involvement admitted to the ICU unit and the complications that may occur following these disorders in the patients. Possible limitations were the retrospective nature of the study and the limited number of patients included. However, our study had several strengths. To date, it is the largest COVID-19 cohort to describe the acid-base status with Stewart’s methodology and the first report of a search for mortality predictors using this innovative approach. Our study population included 211 patients in the year 2020 before vaccination was available. This represented an opportunity to study the clinical and metabolic effects of the virus in a non-immunized population. We also excluded chronic kidney patients and did not detect corticosteroid or alkaline fluid administration before blood gas collection in the ICU, eliminating these potential biases. As the median time from emergency department presentation to ICU admission was 0 d, another possible interference in the acid-base status was very unlikely. Thus, our cohort likely describes the effects of serious COVID-19 on acid-base status.

CONCLUSION

In summary, patients with COVID-19 who were admitted to the hospital had a high incidence of acid-base disorders. They had all types of acid-base changes that were not related to outcomes. The most common acid-base disorders in these patients were metabolic and respiratory alkalosis.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Urology and nephrology

Country of origin: Brazil

Peer-review report’s classification

Scientific Quality: Grade B

Novelty: Grade B

Creativity or Innovation: Grade B

Scientific Significance: Grade B

P-Reviewer: Ait Addi R, Morocco S-Editor: Luo ML L-Editor: A P-Editor: Cai YX

References
1.  Achanti A, Szerlip HM. Acid-Base Disorders in the Critically Ill Patient. Clin J Am Soc Nephrol. 2023;18:102-112.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 9]  [Article Influence: 9.0]  [Reference Citation Analysis (0)]
2.  Hamm LL, Nakhoul N, Hering-Smith KS. Acid-Base Homeostasis. Clin J Am Soc Nephrol. 2015;10:2232-2242.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 208]  [Cited by in F6Publishing: 217]  [Article Influence: 24.1]  [Reference Citation Analysis (0)]
3.  Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020;55:105924.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2988]  [Cited by in F6Publishing: 3039]  [Article Influence: 759.8]  [Reference Citation Analysis (0)]
4.  Durhan G, Ardalı Düzgün S, Baytar Y, Gülsün Akpınar M, Başaran Demirkazık F, Arıyürek OM. Two in one: Overlapping CT findings of COVID-19 and underlying lung diseases. Clin Imaging. 2023;93:60-69.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
5.  Ning Q, Wu D, Wang X, Xi D, Chen T, Chen G, Wang H, Lu H, Wang M, Zhu L, Hu J, Liu T, Ma K, Han M, Luo X. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication. Signal Transduct Target Ther. 2022;7:57.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 37]  [Article Influence: 18.5]  [Reference Citation Analysis (0)]
6.  Alfano G, Fontana F, Mori G, Giaroni F, Ferrari A, Giovanella S, Ligabue G, Ascione E, Cazzato S, Ballestri M, Di Gaetano M, Meschiari M, Menozzi M, Milic J, Andrea B, Franceschini E, Cuomo G, Magistroni R, Mussini C, Cappelli G, Guaraldi G; Modena Covid-19 Working Group (MoCo19). Acid base disorders in patients with COVID-19. Int Urol Nephrol. 2022;54:405-410.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 23]  [Article Influence: 7.7]  [Reference Citation Analysis (0)]
7.  Gunnerson KJ. Clinical review: the meaning of acid-base abnormalities in the intensive care unit part I - epidemiology. Crit Care. 2005;9:508-516.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 60]  [Cited by in F6Publishing: 57]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
8.  Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers. 2021;7:52.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 180]  [Cited by in F6Publishing: 483]  [Article Influence: 161.0]  [Reference Citation Analysis (0)]
9.  Story DA. Stewart Acid-Base: A Simplified Bedside Approach. Anesth Analg. 2016;123:511-515.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 33]  [Cited by in F6Publishing: 33]  [Article Influence: 4.1]  [Reference Citation Analysis (0)]
10.  Rubin DM. Stewart's approach to quantitative acid-base physiology should replace traditional bicarbonate-centered models. J Appl Physiol (1985). 2021;130:2019-2021.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
11.  Chiumello D, Pozzi T, Fratti I, Modafferi L, Montante M, Papa GFS, Coppola S. Acid-Base Disorders in COVID-19 Patients with Acute Respiratory Distress Syndrome. J Clin Med. 2022;11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 1]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
12.  Dzierba AL, Abraham P. A practical approach to understanding acid-base abnormalities in critical illness. J Pharm Pract. 2011;24:17-26.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
13.  Doberer D, Funk GC, Kirchner K, Schneeweiss B. A critique of Stewart's approach: the chemical mechanism of dilutional acidosis. Intensive Care Med. 2009;35:2173-2180.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 45]  [Cited by in F6Publishing: 37]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
14.  Carvalho ARS, Guimarães A, Werberich GM, de Castro SN, Pinto JSF, Schmitt WR, França M, Bozza FA, Guimarães BLDS, Zin WA, Rodrigues RS. COVID-19 Chest Computed Tomography to Stratify Severity and Disease Extension by Artificial Neural Network Computer-Aided Diagnosis. Front Med (Lausanne). 2020;7:577609.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 12]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
15.  Swenson KE, Swenson ER. Pathophysiology of Acute Respiratory Distress Syndrome and COVID-19 Lung Injury. Crit Care Clin. 2021;37:749-776.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 67]  [Cited by in F6Publishing: 73]  [Article Influence: 24.3]  [Reference Citation Analysis (0)]
16.  Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of 'happy' hypoxemia in COVID-19. Respir Res. 2020;21:198.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 313]  [Cited by in F6Publishing: 282]  [Article Influence: 70.5]  [Reference Citation Analysis (0)]
17.  Masevicius FD, Dubin A. Has Stewart approach improved our ability to diagnose acid-base disorders in critically ill patients? World J Crit Care Med. 2015;4:62-70.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 20]  [Cited by in F6Publishing: 12]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
18.  Bezuidenhout MC, Wiese OJ, Moodley D, Maasdorp E, Davids MR, Koegelenberg CF, Lalla U, Khine-Wamono AA, Zemlin AE, Allwood BW. Correlating arterial blood gas, acid-base and blood pressure abnormalities with outcomes in COVID-19 intensive care patients. Ann Clin Biochem. 2021;58:95-101.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 22]  [Article Influence: 5.5]  [Reference Citation Analysis (0)]
19.  Al-Azzam N, Khassawneh B, Al-Azzam S, Karasneh RA, Aldeyab MA. Acid-base imbalance as a risk factor for mortality among COVID-19 hospitalized patients. Biosci Rep. 2023;43.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 5]  [Reference Citation Analysis (0)]