Plasma Ionic Levels in Patients with Septic Shock Before and After Treatment with Different Antioxidants

Research Article

Austin Crit Care Case Rep. 2024; 8(1): 1046.

Plasma Ionic Levels in Patients with Septic Shock Before and After Treatment with Different Antioxidants

Aisa-Álvarez A1#; Soto ME2#; Huesca-Gómez C3; Torres-Paz YE3; Fuentevilla-Álvarez G3; Camarena-Alejo G1; Franco-Granillo J1; Cruz Soto R1; Pérez-Torres I4; Gamboa R4*

1Department of Critical Care, American British Cowdray (ABC) Medical Center, IAP, Mexico

2Research Direction, National Institute of Cardiology and Researcher American British Cowdray (ABC) Medical Center, IAP, Mexico

3Department of Physiology, National Institute of Cardiology “Ignacio Chávez”, México

4Department of Cardiovascular Biomedicine, National Institute of Cardiology “Ignacio Chávez”, México

*Corresponding author: Ricardo Gamboa Physiology Department; National Institute of Cardiology “Ignacio Chávez”. Juan Badiano No. 1. Col. Sección XVI, cp. 14380, México City, México. Email: rgamboaa_2000@yahoo.com

#These authors have been equally contributed to this article.

Received: November 28, 2023 Accepted: January 03, 2024 Published: January 10, 2024

Keywords: Hopkins; Child; Asthma

Abstract

Background: Septic shock is the most severe form of sepsis, and electrolyte levels have been associated with septic shock in intensive care units, although it has been underdiagnosed

Objective: This study aimed to evaluate plasma ionic levels in patients with septic shock before and after treatment with different antioxidants.

Methods: Plasma ionic levels were measured in 129 healthy control patients, 14 with septic shock without treatment, and 51 under treatment with four different antioxidant therapies.

Results: We found essential differences when comparing the plasma ionic levels of K+, Ca2+ y Mg2+ between the control groups versus both groups with sepsis at the time of hospital admission. In patients with septic shock, there is a decrease in the serum levels of ionized Na+, K+, Cl- and Ca2+ and Mg2+ Antioxidant treatment as an adjunct to the standard management of patients with septic shock increases the electrolyte deficit.

Conclusions: The correction of the magnesium deficit also increases serum calcium and potassium levels. Managing antioxidant therapy in patients with septic shock within the first hours of admission can help improve their ionic levels of Ca2+ y Mg2+, mainly in patients with lung damage.

Keywords: Ionized levels; Septic shock; Antioxidants; Ionized magnesium; Ionized calcium

Introduction

Septic shock is the most severe form of sepsis and occurs when it is associated with hypotension and tissue hypo-perfusion. Timely intervention is vital, and identifying risk factors for sepsis on admission can be helpful for patient triage, individualized treatment, and medical decision-making [1].

Serum ion testing is part of the routine comprehensive biochemistry panel, and electrolyte levels associated with septic shock in intensive care units have been underdiagnosed. There are reports [2] that correlate serum magnesium levels (Mg2+) with the admission of patients to the Intensive Care Unit (ICU), the duration of their stay in the ICU, the requirement and duration of mechanical ventilator support, and the outcome of the patient (discharge/death) [3].

The incidence of hypomagnesemia is reported in 2% of the general population, between 10-20% of hospitalized patients, and 50-60% of patients in an intensive care unit [4,5].

The serum magnesium increases the risk of acute respiratory failure, acute kidney injury, and septic shock. Therefore, abnormalities in magnesium levels may affect the prognosis of septic shock.

Another electrolyte recognized as a factor in sepsis is calcium [6]. Calcium exists in three forms or fractions in plasma or serum: ionized (iCa, free calcium), only this fraction is physiologically active, chelated (bound to phosphate, bicarbonate, citrate), and bound to protein. Vitamin D deficiency, "relative" hypoparathyroidism, vitamin D resistance, and 1a hydroxylase deficiency are proposed mechanisms for hypocalcemia in critically ill patients [7]. Average ionic calcium concentrations are between 4.4 and 5.2 mg/dL (1.1-1.3 mmol/L) [8]. Studies carried out in animals demonstrated that interleukin 1β induces hypocalcemia in association with a decrease in Parathyroid Hormone (PTH) and an increase in the expression of Calcium-Sensing Receptors (CASR) in the kidneys and parathyroid [9-11].

Therefore, the measurement of ionized calcium can be critical in determining the actual levels of calcium in an individual's serum. In this way, the recognition of serum electrolytes in patients of the Medical Intensive Care Unit (ICU) may be vital since it could be associated with the severity of the disease or with an increase in mortality and morbidity.

On the other hand, antioxidants have been defined as substances that delay or prevent oxidative when present at low concentrations compared to an oxidizable compound, so many exogenous antioxidants have been used.

Some reports indicate that supplementation with antioxidants helps oxygenation rates, with an increase in glutathione and a more significant immune response [12]. It leads to a reduction in hospital stays and intensive care units, in addition to a decrease in the rates of multi-organ dysfunction and the rate of morbidity and mortality. However, in this regard, more studies in this context are needed and, therefore, require more significant efforts to reinforce the benefits of antioxidant supplementation.

Based on the above, the purpose of this work was to assess the ionic levels of calcium and ionized magnesium, as well as sodium, potassium, and chlorine, in patients with septic shock in an intensive care unit before and after treatment with different antioxidants such as n-acetylcysteine, vitamin C, melatonin, and vitamin E.

Patients and Methods

A case-control clinical trial was carried out. We studied 65 patients > 18 years of age with septic shock in the last 24 hours, characterized by refractory hypotension and requirement for vasopressors, despite adequate fluid resuscitation (20 ml/kg of colloids or 40 ml/kg of crystalloids) to maintain blood pressure = 65 mmHg, included administration with lactate >2 mmol/L. In addition, samples from 129 patients considered as controls were analyzed. Upon hospital admission, the Acute Physiology and Chronic Health Assessment (APACHE) II and SAPS II scores were determined, as well as the Sequential Organ Failure Assessment (SOFA) score and the MEXSOFA organ dysfunction score, for each of the sections (Neurological, respiratory, hemodynamic, hepatic, hematological). The MEXSOFA is a score validated in a Mexican cohort that uses the same sections of the SOFA score with two modifications: PaO2/FiO2 is changed to SpO2/FiO2 and the neurological evaluation is eliminated. A MEXSOFA =9 points during the first hours of admission to the unit have a mortality of 14.8%, while patients with a MEXSOFA =10 points have a mortality of 40%.

Abstract

We obtained signed informed consent from each participant after thoroughly explaining the purpose and nature of all procedures used in the research study, following the provisions of the World Medical Association Declaration of Helsinki. The research was approved by the Ethics, Biosafety and Research Committees of the National Institute of Cardiology (Registration number: INCAR-DG-DI-ACEP-039-2021). The protocol was registered (TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03557229). https://clinicaltrials.gov/ct2/show/NTC03557229?term=aISA+ALFREDO&draw=2&rank=1

Laboratory Analysis

Blood samples were taken from all subjects upon admission to the ICU in sterile tubes with EDTA, tubes with heparin, and tubes with a gel polymer for serum separation. The serum was immediately separated by centrifugation, and the serum electrolytes were determined. Kept the blood samples in the heparin-containing blood tubes on ice and analyzed for ionized Ca2+ and Mg2+ ionized levels using an electrolyte analyzer (Nova Biomedical, Waltham, Mass; USA). The Nova can analyze Na+, K+, Cl- and Ca2+ y Mg2+ ionized. The results were expressed in mmol/L. In addition, we analyzed blood biometry, blood chemistry, liver function tests, c-reactive protein, procalcitonin, and venous and arterial blood gases for each study subject.

Randomization, Masking, and Drug Administration

Patients were randomized and masked into groups to start treatment in the first 24 hours after admission to the ICU and used five treatments, each in an independent group of 18 patients. Group 1 received Vitamin C (Vit C), Group 2 Vitamin E (Vit E), Group 3 N-acetyl Cysteine (NAC), Group 4 Melatonin (MT), and Group 5 control. The control group did not receive treatment since the treating physician disagreed with the patient receiving any antioxidants. All antioxidants were administered orally or through a nasogastric tube for five days in addition to the standard therapy. The random allocation sequence for administering the antioxidants was generated at the coordinating center using a computer-generated random program. Blinding was maintained by the investigational pharmacy at each institution. Researchers were also blinded from the study's onset until the outcomes analysis.

After each treatment, we performed the same blood and electrolyte tests.

The doses of antioxidants were chosen according to what has been reported in the literature [13-16]. All data entry was monitored at the coordinating center, with site visits for source data verification. Also, patients were equally distributed, and all patients were analyzed.

Groups:

1) For the N-acetyl cysteine group, two effervescent tablets of 600 mg of N-acetyl cysteine (1200 mg) were administered every 12 hours by oral route or naso-enteral tube for five days.

2) For the melatonin group, melatonin was administered in 5 mg prolonged-release capsules at night, at 50 mg (10 capsules) orally or by naso-enteral tube for five days.

3) For the vitamin C group, 1-gram vitamin C tablets were used, which were administered every 6 hours by oral route or naso-enteral tube for five days.

4) For the vitamin E group, vitamin E (d-alpha tocopheryl acetate) capsules of 1200 IU equivalent to 1200 mg were used, which were administered every 24 hours for five days.

5) Control groups. This group did not receive any antioxidant therapy.

Statistical Analysis

The SPSS 21 program was used for statistical analysis. The Student's t test was used to evaluate the differences between the mean values obtained between the groups. An ANOVA test was used to compare plasma ion concentrations. Pearson's chi2 test or Fisher's exact test was used for standard data. The Shapiro-Wilk test was used to determine whether the distributions of the variables were normal. Numerical data are shown as mean±SD and nominal data are reported as percentages; a logarithmic transformation was applied for ionized Mg2+ levels due to the non-normal distribution of the variables. The value of p<0.05 was considered statistically significant. The STROBE case-control reporting guidelines [17] were used.

Results

One hundred ninety-four subjects were studied: 129 healthy control patients, 14 patients with septic shock without treatment and 51 on treatment with antioxidants. The mean age of healthy patients was 35.4±12.04, which showed a statistically significant difference compared to patients with sepsis without treatment, 73.0±10.49 (p=0.000) and with treatment, 64.16.±17.38 (p=0.000), these last two groups being older; There were no significant differences between the two groups with septic shock with and without treatment (p=0.096). Regarding gender and BMI, no statistically significant differences were found between the three study groups. When comparing our two groups with septic shock, we found significant differences in the APACHE II score (p=0.039) and in the assessment of the risk of malnutrition (p=0.020) (Table 1).