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Supplemental Digital Content is available in the text., Lithium, a mood stabilizer used in the treatment of bipolar disorder is known for its anti-inflammatory properties with the discussion of its potential use in COVID-19 infection. The SARS-CoV-2 virus causing COVID-19 infection is known to enter the target cells through angiotensin converting enzyme-2 receptors present in abundance in the lung and renal tissue. Recent research supports the evidence for direct renal injury by viral proteins. Here we report two patients with bipolar disorder presenting with lithium toxicity in the presence of COVID-19 infection. Two patients with bipolar disorder, maintaining remission on lithium prophylaxis, presented to the psychiatric emergency with recent-onset fever and altered sensorium. Both the patient’s investigations revealed lithium toxicity, elevated serum creatinine, urea and inflammatory markers. Hypernatremia, hyperkalaemia, and hyperchloremia were seen in one patient. Lithium and other psychotropic medications were stopped immediately, and COVID-19 treatment was initiated. Patient with clinical signs of lithium toxicity, hypernatremia, hyperkalaemia, and hyperchloremia developed ventricular tachycardia. He survived and regained consciousness after 2 weeks of aggressive conservative management. However, another patient died of acute respiratory failure on day 3. Possible direct infection of the kidney by SARS-CoV-2 viral proteins can manifest with acute kidney injury and lithium toxicity among patients on long-term lithium therapy. Health professionals treating COVID-19 infection among individuals on lithium therapy should be aware of the possibility of lithium toxicity in the background of renal injury.

Background Intravenous fluid therapy represents the most common intervention critically ill patients are exposed to. Hyperchloremia and metabolic acidosis associated with 0.9% sodium chloride have been observed to lead to worse outcomes, including mortality. Balanced solutions, such as Plasma-Lyte 148 and Compound Sodium Lactate, represent potential alternatives but the evidence on optimal fluid choices in critically ill children remains scarce. This study aims to demonstrate whether balanced solutions, when used as intravenous fluid therapy, are able to reduce the incidence of a rise in serum chloride level compared to 0.9% sodium chloride in critically ill children. Methods This is a single-centre, open-label randomized controlled trial with parallel 1:1:1 assignment into three groups: 0.9% sodium chloride, Plasma-Lyte 148, and Compound Sodium Lactate solutions for intravenous fluid therapy. The intervention includes both maintenance and bolus fluid therapy. Children aged < 16 years admitted to intensive care and receiving intravenous fluid therapy during the first 4 h of admission are eligible. The primary outcome measure is a ≥ 5mmol/L increase in serum chloride level within 48 h post-randomization. The enrolment target is 480 patients. The main analyses will be intention-to-treat. Discussion This study tests three types of intravenous fluid therapy in order to compare the risk of hyperchloremia associated with normal saline versus balanced solutions. This pragmatic study is thereby assessing the most common intervention in paediatric critical care. This is a single-centre open-label study with no blinding at the level of delivery of the intervention. Certain paediatric intensive care unit (PICU) patient groups such as those admitted with a cardiac condition or following a traumatic brain injury are excluded from this study. Trial registration The study has received ethical approval (HREC/19/QCHQ/53177: 06/06/2019). It is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619001244190) from 9th September 2019. Recruitment commenced on 12th November 2019. The primary results manuscript will be published in a peer-reviewed journal.

Objective Chloride is an important electrolyte in the body. In this study, we aimed to evaluate the associations between chloride levels on emergency department (ED) admission and neurologic outcomes by stratifying patients undergoing targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) into three groups (hyper/normo/hypochloremia); we also assessed the effect of changes in chloride levels from baseline over time on outcomes. Methods This retrospective, observational cohort study of 346 patients was conducted between 2011 and 2019. The chloride levels were categorized as hypochloremia, normochloremia, and hyperchloremia by predetermined definitions. The primary endpoint was poor neurologic outcomes after hospital discharge. We evaluated the associations between chloride levels on ED admission and neurologic outcomes and assess the effect of changes in chloride levels over time on clinical outcomes. Results On ED admission, compared with normochloremia, hypochloremia was significantly associated with unfavorable neurologic outcomes (OR, 2.668; 95% CI, 1.217–5.850, P = 0.014). Over time, unfavorable neurologic outcomes were significantly associated with increases in chloride levels in the hyperchloremia and normochloremia groups after ED admission. The rates of poor neurologic outcomes in the hyperchloremia and normochloremia groups were increased by 14.2% at Time-12, 20.1% at Time-24, and 9.3% at Time-48 with a 1-mEq/L increase in chloride levels. Conclusion In clinical practice, chloride levels can be routinely and serially measured cost-effectively. Thus, baseline chloride levels may be a promising tool for rapid risk stratification of patients after OHCA. For fluid resuscitation after cardiac arrest, a chloride-restricted solution may be an early therapeutic strategy.

Background The debate for the optimum sodium concentration in the rehydration solution in diabetic ketoacidosis (DKA) persists till the moment. The aim was to compare the outcome of 0.9% saline versus 0.45% saline in children with moderate and severe (DKA) regarding the effect on serum electrolytes, duration of DKA resolution and the incidence of hyperchloremia. Results A retrospective analysis of 121 children with moderate or severe DKA was done. After the initial 4 h in which both groups received normal saline, patients were divided into two groups continuing on 0.9% (N=72) or switched to 0.45% saline (N=49). Serum chloride and Cl/Na ratios were significantly higher in 0.9% saline group at 4 and 8 h. The 0.9% saline group had significantly higher proportion of hyperchloremia at 4 and 8 h (P value: 0.002, 0.02). The median duration of correction of DKA (14 h among 0.9% saline versus 10 h among 0.45% saline) without significant difference (P value= 0.43). The change in plasma glucose, effective osmolarity, corrected Na levels were comparable between groups. Conclusion There is an unavoidable iatrogenically induced rise in serum chloride with higher incidence of hyperchloremia with the use of normal saline in rehydration of children presenting in DKA and shock. The use of 0.45% saline as post-bolus rehydration fluid is not associated with a decline in the corrected serum sodium concentration and does not affect the rate of correction of acidosis or rate of drop in blood glucose or duration of DKA resolution when compared to normal saline.

Mortalitas sepsis dan syok sepsis hampir 20% per tahun dari semua kematian global. Sepsis dan syok sepsis merupakan penyebab 50% pasien dirawat di Intensive Care Unit (ICU). Kristaloid menjadi terapi cairan yang tepat menurut “The Surviving Sepsis Campaign Bundle: 2018 (SSC 2018)”. Kristaloid terbagi menjadi dua jenis, yaitu balanced dan unbalanced crystalloids. Perbedaan kandungan elektrolit keduanya dapat memengaruhi outcome pasien. Penelitian ini bertujuan mengetahui perbedaan pengaruh balanced dan unbalanced crystalloids pada sepsis dan syok sepsis dalam aspek mortalitas, kejadian hiperkloremia, dan lama tinggal di rumah sakit (RS). Metode yang digunakan adalah systematic review. Tempat penelitian berupa pencarian artikel penelitian pada online database dengan waktu penelitian, yaitu artikel dari tahun 2017 hingga 2021. Seleksi studi menggunakan PRISMA, kirteria restriksi dan PICO. Telaah artikel didapatkan 6 dari 249 artikel yang memenuhi syarat. Hasil analisis adalah mortalitas lebih rendah pada grup balanced crystalloids, kejadian hiperkloremia lebih tinggi pada unbalanced crystalloids, namun lama tinggal di RS di kedua grup tidak ada perbedaan signifikan. Simpulan penelitian adalah balanced crystalloids lebih efektif daripada unbalanced crystalloids dalam aspek menurunkan mortalitas dan kejadian hiperkloremia, namun tidak mengenai lama tinggal. Differences in the Effect of Balanced and Unbalanced Crystalloids as Fluid Therapy in Sepsis and Septic Shock: A Systematic Review Sepsis and septic shock contribute to almost 20% per year to the global total deaths. Sepsis and septic shock are also the the leading causes for patients to be treated in the Intensive Care Unit (ICU), with 50% of the patients treated in this unit due to sepsis and septic shock. Crystalloid is the appropriate thereapy for these conditions according to “The Surviving Sepsis Campaign Bundle: 2018 (SSC 2018)”. Crystalloids are divided into two types: balanced and unbalanced crystalloids. This study aimed to determine the difference between the effects of balanced and unbalanced crystalloids in sepsis and septic shock in terms of mortality, incidence of hyperchloremia, and length of stay in hospital. This was a systematic review on articles from the last five years using PRISMA, restriction criteria, and PICO. The review resulted in 6 out of 249 eligible articles. The results of the analysis demonstrated a lower mortality rate in the balanced crystalloids group while the incidence of hyperchloremia was higher in the unbalanced crystalloids group. No significant difference was found in the length of stay in hospital in both groups. Therefore, balanced crystalloids is more effective than unbalanced crystalloids in the aspect of reducing mortality and the incidence of hiperchloremia, with no significant difference in the length of stay in hospital.

Background: The relationship between perioperative hyperchloremia and postoperative acute kidney injury (AKI) is not well established. Our study aimed to evaluate the association between perioperative hyperchloremia and acute kidney injury in patients undergoing off-pump coronary artery bypass grafting (CABG). Methods: Patients with coronary disease who underwent off-pump CABG between April 2017 and December 2019 were enrolled in this retrospective study. The patients with perioperative hyperchloremia were matched 1:1 to patients without perioperative hyperchloremia. The primary outcome was the postoperative acute kidney injury rate. The secondary outcomes included intensive care unit (ICU)-free days, postoperative hospitalization days, wound infection rate, and in-hospital mortality. Propensity score matching and univariate and multivariate logistic regression analyses were used in this study. Results: A total of 321 patients who underwent off-pump CABG were included in the analysis. Propensity score matching selected 83 pairs for the final comparison. The results showed that the postoperative AKI rate was significantly different between the hyperchloremia and no hyperchloremia groups (56.6% versus 15.7%; P < .001). The number of ICU-free days, postoperative hospitalization days, wound infection rate, and in-hospital mortality were similar between the two groups. In the multivariable, logistic regression analysis, hyperchloremia was independently associated with the development of postoperative AKI (odds ratio [OR] = 1.814, 95% confidence interval [CI]: 1.072-3.070, P = .026). Conclusions: Perioperative hyperchloremia is associated with an increase in the postoperative AKI rate among patients undergoing off-pump CABG.

Um marco importante na medicina foi o desenvolvimento dos fluidos intravenosos. Obteve-se impacto imediato nos desfechos de doenças, como a cólera, e nos pacientes politraumatizados. Sua importância desencadeou um interesse pelo estudo da fisiologia e anatomia da macro e microcirculação, criação de novos fluidos, bem como o impacto do tipo das soluções sobre os desfechos clínicos. A solução salina, popularizada como solução fisiológica ou normal, é uma das soluções mais antigas e mais utilizadas no mundo. As soluções balanceadas, como o Plasma-lyte®, Ringer Lactato, entre outros, que utilizam tampões e ânions fracos na composição, começaram a ser apresentadas e se mostraram mais fisiológicas e com desfechos clínicos melhores em uma variedade extensa de pacientes. As descobertas da anatomia e fisiologia da microcirculação, alterações hidroeletrolíticas e ácido-básicas específicas de cada doença, hipercloremia e seus malefícios trouxeram uma discussão ampla e importante na indicação de cada cristaloide. O tipo e a quantidade de fluido a ser administrada no perioperatório têm impacto direto no desfecho dos pacientes. As soluções balanceadas vêm se apresentando como alternativa superior à solução salina 0,9% no contexto perioperatório.

Introduction: Hypernatremia can cause encephalopathy, rhabdomyolysis, and osmotic demyelination. Postpartum hypernatremia is an uncommon occurrence. The present study attempts to highlight clinical and radiological profile of three patients who had postpartum hypernatremia and to provide differential diagnosis of magnetic resonance imaging findings of postpartum hypernatremia. Aim:To study clinical and radiological profile of three patients who had postpartum hypernatremia and to provide differential diagnosis of magnetic resonance imaging findings of postpartum hypernatremia. Material and Methods:The present study was conducted in a tertiary care centre in South India between March 2014 to March 2018. Three patients had hypernatremia presenting in postpartum period. Demographic data, clinical details, results of laboratory examinations and neuroimaging details of these patients were recorded. Result:All three patients had hypernatremia presenting with encephalopathy. Spasticity was seen in all patients. Quadriparesis was seen in two patients. One patient had generalized tonic clonic seizures. Two patients had hypokalemia. All the three patients had Hyperchloremia, Azotemia and raised serum osmolality. Phosphorous levels was high in one patient. Creatine kinase levels was high in one patient. All patients had hypermagnesemia and normal calcium levels. Thrombocytopenia was seen in one patient. On neuroimaging, splenium of corpus callosum, hippocampus and posterior limb of internal capsule were involved in all patients. Cerebral peduncles in two patients. Corona Radiata and cerebellar white matter were involved in one patient. Conclusion:Early identification and meticulous management of hypernatremia is of paramount importance. Neuroimaging Findings in postpartum hypernatremia is distinct. Keywords: Postpartum, Hypernatremia, Encephalopathy, Osmotic demyelination, rhabdomyolysis.

Background This systematic review discusses a clinical physiology aspect of chloride in fluid therapy. Crystalloid solutions are one of the most widely used remedies. While generally used in medicine for almost 190 years, studies focused largely on their safety have only been published since the new millennium. The most widely used solution, normal saline, is most often referred to in this context. Its excessive administration results in hyperchloremic metabolic acidosis with other consequences, including higher mortality rates. Methods Original papers and review articles eligible for developing the present paper were identified by searching online in the electronic MEDLINE database. The keywords searched for included hyperchloremia, hypochloremia, and compound words containing the word “chloride,” infusion therapy, metabolic acidosis, renal failure, and review. Results A total of 21,758 papers published before 31 May 2020 were identified; of this number, 630 duplicates were removed from the list. Upon excluding articles based on their title or abstract, 1850 papers were screened, of which 63 full-text articles were assessed. Conclusions According to the latest medical concepts, dyschloremia (both hyperchloremia and hypochloremia) represents a factor indisputably having a negative effect on selected variables of clinical outcome. As infusion therapy can significantly impact chloride homeostasis of the body, the choice of infusion solutions should always take into account the potentially adverse impact of chloride content on chloremia and organ function.

BackgroundIncreased chloride in the context of intravenous fluid chloride load and serum chloride levels (hyperchloremia) have previously been associated with increased morbidity and mortality in select subpopulations of intensive care unit (ICU) patients (e.g patients with sepsis). Here, we study the general ICU population of the Medical Information Mart for Intensive Care III (MIMIC-III) database to corroborate these associations, and propose a supervised learning model for the prediction of hyperchloremia in ICU patients.MethodsWe assessed hyperchloremia and chloride load and their associations with several outcomes (ICU mortality, new acute kidney injury [AKI] by day 7, and multiple organ dysfunction syndrome [MODS] on day 7) using regression analysis. Four predictive supervised learning classifiers were trained to predict hyperchloremia using features representative of clinical records from the first 24h of adult ICU stays.ResultsHyperchloremia was shown to have an independent association with increased odds of ICU mortality, new AKI by day 7, and MODS on day 7. High chloride load was also associated with increased odds of ICU mortality. Our best performing supervised learning model predicted second-day hyperchloremia with an AUC of 0.76 and a number needed to alert (NNA) of 7—a clinically-actionable rate.ConclusionsOur results support the use of predictive models to aid clinicians in monitoring for and preventing hyperchloremia in high-risk patients and offers an opportunity to improve patient outcomes.

Our objective was to determine in children in the intensive care unit (ICU) the incidence of hyperchloremia (>110 mmol/L) and hypochloremia (

Objectives To investigate the acid‐base status of sick goats using the simplified strong ion difference (sSID) approach, to establish the quantitative contribution of sSID variables to changes in blood pH and HCO3 − and to determine whether clinical, acid‐base, and biochemical variables on admission are associated with the mortality of sick goats. Animals One hundred forty‐three sick goats. Methods Retrospective study. Calculated sSID variables included SID using 6 electrolytes unmeasured strong ions (USI) and the total nonvolatile buffer ion concentration in plasma (Atot). The relationship between measured blood pH and HCO3 −, and the sSID variables was examined using forward stepwise linear regression. Cox proportional hazard models were constructed to assess associations between potential predictor variables and mortality of goats during hospitalization. Results Hypocapnia, hypokalemia, hyperchloremia, hyperlactatemia, and hyperproteinemia were common abnormalities identified in sick goats. Respiratory alkalosis, strong ion acidosis, and Atot acidosis were acid‐base disorders frequently encountered in sick goats. In sick goats, the sSID variables explained 97% and 100% of the changes in blood pH and HCO3 −, respectively. The results indicated that changes in the respiratory rate (

Background: 0.9% saline commonly used for resuscitation of septic patients might induce biochemical changes leading to detrimental effects. Ringer’s lactate being a balanced crystalloid might be beneficial in such a scenario. Objectives: We undertook this study to explore in detail the effect of these fluids in the resuscitation of septic patients, and risks and benefits these two fluids would have on the overall prognosis of patients. Methods: This was an open-label randomized controlled trial undertaken in emergency medical services attached to the department of medicine at a tertiary care teaching hospital. One hundred sixty adult (⩾18 years old) medical patients admitted with the diagnosis of sepsis fulfilling eligibility criteria were included. They were randomly assigned to receive 0.9% saline or ringer’s lactate. These fluids were given for the initial 24 h only, and after then, the type of fluid given was based on treating physician discretion. Various biochemical parameters were measured at baseline and various time points during the hospital stay. The primary outcome was to find out the incidence of hyperchloremia at 24 h from the time of randomization and during the hospital stay. The secondary outcomes were incidence of acute kidney injury, need for renal replacement therapy; differences in pH, bicarbonate, serum lactate, coagulation parameters, sequential organ failure assessment scores at various time points; and hospital/30-day mortality. Results: The baseline characteristics in both groups were comparable. At admission, each group had a serum chloride value which was comparable ( p value: 0.595); however, at 24 and 48 h, a statistically significant difference was noticed, with 0.9% saline group having a higher mean serum chloride value (113.66 ± 10.04 v/s 108.98 ± 8.04 mEq/L, p value: 0.001 at 24 h) and (114.75 ± 9.51 v/s 111.12 ± 7.84 mEq/L, p value: 0.022 at 48 h). At 24 and 48 h post-randomization, the incidence of hyperchloremia was significantly higher in the 0.9% saline group (at 24 h, 0.9% saline: 75.0% v/s Ringer’s lactate: 48.8%, p value: 0.001 and at 48 h, 0.9% saline: 77.2% v/s Ringer’s lactate: 60.3%, p value: 0.022), although there was no difference in the incidence of hyperchloremia recorded during the hospital stay. Acute kidney injury incidence at 24 and 48 h post-randomization was significantly higher in the 0.9% saline group (at 24 h, 0.9% saline: 23.8% v/s Ringer’s lactate: 10.0%, p value: 0.020 and at 48 h, 0.9% saline: 29.1% v/s Ringer’s lactate: 15.4%, p value: 0.039). No significant differences in other secondary outcomes were observed. Conclusion: Higher incidence of hyperchloremia and a higher rate of acute kidney injury at 24 and 48 h after randomization were noted in the 0.9% saline group.

Purpose To evaluate whole blood chloride concentration and hospital-acquired AKI in hospitalized canine patients. Secondary outcome measures included the volume-adjusted chloride load, in-hospital mortality and length of ICU stay. Patients and Methods This is a prospective, observational study. Sixty dogs admitted to the ICU and receiving IV fluid therapy for >24 hours from February 2018 to July 2019. Corrected chloride and creatinine concentrations were obtained twice daily. Total volume of IV fluid and total chloride load were recorded. Volume-adjusted chloride load (VACL) was calculated by dividing the chloride administered by the volume of fluid administered. Hospital-acquired AKI was defined as an increase in creatinine of ≥26.5 μmol/L (0.3 mg/dL) or 150% from baseline to maximum. Survival to hospital discharge or non-survival and ICU length of stay were also recorded. Results Fifteen out of 60 patients developed hospital-acquired AKI. Maximum corrected chloride was significantly different in AKI group (median 122.3 mmol/L) vs non-AKI group (median 118.1 mmol/L; p=0.0002). Six out of 60 patients developed hyperchloremia. Hyperchloremic patients were significantly more likely to develop in-hospital AKI (p=0.03). Patients hospitalized ≥2 days had a significantly higher [Cl-]max compared to those with shorter ICU stay (121.8 ± 5.9 mmol/L vs 117.5 ± 4.3 mmol/L; p=0.002). Eight out of 60 patients were non-survivors. Maximum corrected chloride and creatinine concentrations were not significantly different between survivors and non-survivors. VACL was not significantly different between AKI or mortality groups. Conclusion Maximum corrected chloride concentration was significantly higher in dogs with hospital-acquired AKI, even amongst dogs without hyperchloremia. Additionally, maximum corrected chloride concentrations were significantly higher in dogs hospitalized in the ICU longer compared to those hospitalized for fewer than two days. There was no significant difference in VACL in any of the outcome groups. Results from this study suggest alterations in chloride may be observed alongside the development of acute kidney injuries. Future studies in critically ill dogs are warranted.

Objective : Assessment of gas and electrolytic composition of venous blood in patients with chronic obstructive pulmonary disease (COPD) in relation to basic parameters of functional state of kidneys. Methods : 60 patients with COPD were divided into low and high exacerbation risk groups and were examined. Standard examinations were carried out; electrolytic and gas composition of venous blood and kidney functions were assessed. Results : Patients with high risk of COPD exacerbation demonstrated symptoms of respiratory failure, hyperchloremia, higher levels of potassium and albuminuria; there was a relationship between albuminuria and oximetric parameters. A significant dependence between glomerular filtration rate and COPD exacerbation rate was not detected, but there was its relationship with the smoking index, the result of the CAT questionnaire, Gensler index, instantaneous expiratory flow rate, lung capacity and peak expiratory flow rate were recorded. Conclusions : COPD is often characterized by combination of gas and electrolytic composition imbalance of venous blood and renal dysfunction. With a high risk of exacerbations, signs of respiratory failure, hyperchloremia, higher levels of potassium and albuminuria are more often observed. The relationship between daily albuminuria and oximetric parameters, glomerular filtration rate and partial blood oxygen tension, found in people at high risk of COPD exacerbation may indicate the need for correction of blood gas composition to prevent renal dysfunction.

BACKGROUND Electrolyte balance plays key role in maintaining homeostasis along with fluids in paediatric patients. The higher and lower value of critical electrolytes like sodium, potassium and chloride can affect cellular processes drastically as it may result in cardiac and neurological complications. This can alter patient status in terms of morbidity and mortality. Hence, Electrolyte imbalance significantly affects the quality of life of the patient. In this study we have analysed three electrolytes; sodium, potassium and chloride. The accurate measurement of electrolytes is an important prognostic indicator in PICU patients where greater attention and proper analysis is recommended. METHODS 180 paediatric patients in the age group of 2-15 years with various critical illnesses admitted in PICU of a tertiary care hospital were included in the study. The serum samples were analysed on Transasia Biomedicals XL 640 – a fully automated biochemistry analyser which has Ion Selective Electrode (ISE-Na/K/Cl) and diffraction grating for high resolution measurement. RESULTS Out of the 180 paediatric patients enrolled for the study, 83 were females and 97 were males. Hypernatremia was observed in 35% patients while hyponatremia in 31%. Hyperkalaemia was observed in 27% patients while hypokalaemia in 14%. Hyperchloremia in 24% while hypochloraemia 5% patients. CONCLUSIONS The electrolyte balance plays a key role in treatment of patients admitted in PICU. The accurate measurement of electrolyte like sodium, potassium & Chloride is an important prognostic indicator where greater attention and proper analysis is recommended. Also, the presence of electrolyte imbalance at the time of admission is an important prognostic indicator in critically ill children irrespective of primary disease process and needs to be addressed aggressively. The study helped us in maintaining the electrolyte ‘homeostasis’ in the body which is vital for the organ’s support and optimal function and also evaluating therapies and matching severity of illness in the PICU.

Hypernatremia has been associated with mortality in neurocritically ill patients, with and without traumatic brain injury (TBI). These studies, however, lack concomitant adjustment for hyperchloremia as a physiologically co-occurring finding despite the associations with hyperchloremia and worse outcomes after trauma, sepsis, and intracerebral hemorrhage. The objective of our study was to examine the association of concomitant hypernatremia and hyperchloremia with in-hospital mortality in moderate–severe TBI (msTBI) patients. We retrospectively analyzed prospectively collected data from the OPTIMISM-study and included all msTBI patients consecutively enrolled between 11/2009 and 1/2017. Time-weighted average (TWA) sodium and chloride values were calculated for all patients to examine the unadjusted mortality rates associated with the burden of hypernatremia and hyperchloremia over the entire duration of the intensive care unit stay. Multivariable logistic regression modeling predicting in-hospital mortality adjusted for validated confounders of msTBI mortality was applied to evaluate the concomitant effects of hypernatremia and hyperchloremia. Internal bootstrap validation was performed. Of the 458 patients included for analysis, 202 (44%) died during the index hospitalization. Fifty-five patients (12%) were excluded due to missing data. Unadjusted mortality rates were nearly linearly increasing for both TWA sodium and TWA chloride, and were highest for patients with a TWA sodium > 160 mmol/L (100% mortality) and TWA chloride > 125 mmol/L (94% mortality). When evaluated separately in the multivariable analysis, TWA sodium (per 10 mmol/L change: adjusted OR 4.0 [95% CI 2.1–7.5]) and TWA chloride (per 10 mmol/L change: adjusted OR 3.9 [95% CI 2.2–7.1]) independently predicted in-hospital mortality. When evaluated in combination, TWA chloride remained independently associated with in-hospital mortality (per 10 mmol/L change: adjusted OR 2.9 [95% CI 1.1–7.8]), while this association was no longer observed with TWA sodium values (per 10 mmol/L change: adjusted OR 1.5 [95% CI 0.51–4.4]). When concomitantly adjusting for the burden of hyperchloremia and hypernatremia, only hyperchloremia was independently associated with in-hospital mortality in our msTBI cohort. Pending validation, our findings may provide the rationale for future studies with targeted interventions to reduce hyperchloremia and improve outcomes in msTBI patients.

BACKGROUND: IV vancomycin is widely used for infections caused by Gram-positive bacteria; however, nephrotoxicity is commonly associated with its use. Clinical trials have shown an increased incidence of acute kidney injury (AKI) using normal saline (NS) for fluid resuscitation. This study evaluated differences in AKI and other patient outcomes associated with vancomycin diluted in NS compared with dextrose 5% in water (D5W). METHODS: This retrospective cohort study conducted at a single US Department of Veterans Affairs hospital included veterans who received vancomycin for at least 48 hours between July 1, 2015 and June 30, 2020. This study compared adverse events (AEs) of patients receiving vancomycin diluted in either NS or D5W. The primary outcome was incidence of AKI. Secondary outcomes included incidence of hyperglycemia, hyperchloremia, hypernatremia, metabolic acidosis, in-hospital mortality, and 30-day posthospitalization mortality. RESULTS: The study included 123 patients in each group (N = 246). The percentage of AKI was 22.8% in the D5W group compared with 14.6% the NS group (P = .14). There were no significant differences in the rates of hyperglycemia, hyperchloremia, hypernatremia, or metabolic acidosis between the 2 groups. In-hospital mortality and 30-day posthospitalization mortality were similar between the groups. CONCLUSIONS: This study comparing the AEs of IV vancomycin diluted in NS and D5W found no significant differences in AKI or other patient outcomes. These study results do not suggest the crystalloid used to dilute IV vancomycin is associated with differences in nephrotoxicity or other relevant AEs.

In the second part of the review, aspects of changes in magnesium metabolism under conditions of severe stress, mechanisms of anti-stress protection of the body with the participation of magnesium, features of magnesium participation in water-electrolyte metabolism at the cellular level, the anti-inflammatory effect of magnesium and the role of magnesium in the processes of detoxification of the body in acute poisoning with certain poisons are consi-dered. The main mechanisms of the body’s magnesium defence are to suppress the mechanisms of oxidative stress by limiting the production of stress hormones, the intake of ionized calcium and sodium into cells with a decrease in the severity of transmineralization and sodium retention in the body, suppressing the action of factors that initiate the development of inflammation and reducing the production of pro-inflammatory mediators, in blocking and protecting glutamate receptors. Magnesium therapy can help keep effective energy production in the body in critical conditions by maintaining the functioning of the Na+/K+-ATPase, the work of the Na+/H+-exchanger, helping reduce the severity of cellular acidosis. The mechanisms of functioning and the prescription of the sodium-magnesium antiporter are discussed. Hypertonic solutions of magnesium sulfate are being injected at a high rate to create the effect of rapid low-volume fluid resuscitation, thereby eliminating the dangerous effects of severe hyperchloremia and hypernatremia that occur when using hypertonic sodium chloride solutions. In toxico-logy, magnesium preparations are used to protect the body when exposed to heavy metals, organophosphorus compounds. They also help reduce the severity of oxidative stress caused by heavy metals, inhibit excess production of endogenous carbon monoxide, and limit free radical damage in its pathological effect. During detoxification, magnesium prevents depletion of the antioxidant system by helping maintain sufficient levels of glutathione and other antioxidants in cells., У другій частині огляду розглядаються аспекти змін магнієвого обміну в умовах тяжкого стресу, механізми антистресового захисту організму за участю магнію, особливості участі магнію у водно-електролітному обміні на рівні клітини, протизапальний ефект магнію і його роль у процесах детоксикації організму при гострих отруєннях деякими отрутами. Основні механізми магнієвого захисту організму полягають у пригніченні механізмів окисного стресу за рахунок обмеження продукції стресових гормонів, обмеження надходження до клітин іонізованого кальцію і натрію зі зменшенням тяжкості трансмінералізації і затримки натрію в організмі, у пригніченні дії факторів, що ініціюють розвиток запалення, і в зменшенні продукції прозапальних медіаторів, у блокуванні та захисті глутаматних рецепторів. Магнезіальна терапія може сприяти збереженню ефективної енергетичної продукції в організмі при критичних станах за рахунок підтримки функціонування Na+/K+-АТФази, підтримки роботи Na+/H+-ексченджера, сприяючи зменшенню тяжкості клітинного ацидозу. Обговорюється механізм функціонування та призначення натрієво-магнієвого антипорту. Гіпертонічні розчини магнію сульфату вводять у високому темпі для створення ефекту швидкої малооб’ємної рідинної ресусцитації, виключаючи тим самим небезпечні ефекти тяжкої гіперхлоремії і гіпернатріємії, що виникають при застосуванні гіпертонічних розчинів натрію хлориду. У токсикології препарати магнію використовуються для захисту організму при впливі важких металів, фосфорорганічних сполук. Вони також перешкоджають окисному стресу, який створюють важкі метали, сприяють зменшенню продукції ендогенного монооксиду вуглецю і обмежують вільнорадикальні пошкодження при його патологічному впливі. При детоксикації магній попереджає виснаження антиоксидантної системи, сприяючи збереженню в клітинах достатнього рівня глутатіону та інших антиоксидантів.

A 4-month-old male indoor cat was referred for dyspnea, mental dullness and weakness, which appeared two days earlier. The cat had been adopted at 3 months of age. Physical exam showed cyanosis, dyspnea and mild hypothermia. The “spot test” was supportive of methemoglobinemia. Co-oximetry blood gas analysis revealed severe methemoglobinemia (81.40%), severe hyperchloremia and mild hyponatremia. CBC, biochemistry and urinalysis were within normal limits, blood smear showed the presence of Heinz bodies. Treatment was instituted with oxygen therapy, methylene blue 1% solution, ascorbic acid, intravenous fluid therapy. The clinical course was favorable with rapid improvement of cyanosis and methemoglobinemia (4.2%). Acquired methemoglobinemia was hypothesized. Two weeks after discharge the cat was asymptomatic but mild methemoglobinemia (15.60%) and hyperchloremia were evident. Exposure to oxidants contained in drinking water was suspected so the owners were instructed to use bottled water only. One month later the cat was asymptomatic, and methemoglobinemia and chloremia were within normal limits. Even if a congenital form due to cytochrome b5 reductase deficiency cannot be ruled out, drinking water intoxication is the most likely cause of methemoglobinemia in this cat.

Background The importance of optimal acid-base balance during renal transplant surgeries cannot be stressed enough. Optimal preload and electrolyte balance is important in maintaining this. There has been a debate on the choice of perioperative crystalloids in renal transplant surgeries over the past decades. Normal saline (0.9% saline) is more likely to cause hyperchloremic acidosis when compared to balanced salt solutions (BSS) with low chloride content whereas BSS may cause hyperkalemia. We aim to compare the safety and efficacy of normal saline (NS), Ringer’s lactate (RL) and Plasmalyte (PL) on acid-base balance and electrolytes during living donor kidney transplantation. Materials and methods Patients were randomized to NS group (n = 60), RL group (n = 60) and Plasmalyte group (n = 60). Arterial blood samples were collected for acid-base analysis after induction of anaesthesia (T0), prior to clamping the iliac vein (T1), 10 minutes after reperfusion of the donated kidney (T2) and at the end of surgery (T3). In addition, serum creatinine and 24-hour urine output were recorded on postoperative days one, two and seven. Results There was a statistically significant difference (p < 0.001) in the pH at the end of surgery between the three groups with the NS group being more acidotic (pH 7.29 ± 0.06, 95% CI 7.27-7.32), although this was not clinically relevant. This was explainable by the parallel increase in chloride in the NS group. Early postoperative graft functions in terms of serum creatinine, urine output and graft failure requiring dialysis were not significantly different between the groups. Conclusion Balanced salt solutions such as Plasmalyte and Ringer’s lactate are associated with better pH and chloride levels compared to normal saline when used intraoperatively in renal transplant patients. This difference, however, does not appear to have any bearing on graft function. Plasmalyte seems to maintain a better acid-base and electrolyte balance, especially during the postreperfusion period.

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of &gt, 108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster’s key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33–5.56) for cluster 1, and 4.83 (95% CI 3.21–7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53–5.70) for cluster 1 and 6.96 (95% CI 5.56–8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.

Introduction: Yellow oleander (Thevetia peruviana), which belongs to the Apocyanaceae family, is a common shrub seen throughout the tropics. All parts of the plant contain high concentrations of cardiac glycosides which are toxic to cardiac muscle and the autonomic nervous system. Here, we describe the clinical profile of patients with oleander poisoning and their outcomes. Methods and Materials: This retrospective study was conducted over a period of 12 months (March 2016 to February 2017). The data was extracted from the inpatient electronic medical records. Adult patients with a diagnosis of acute yellow oleander poisoning were included in the study. Descriptive statistics were obtained for all variables in the study and appropriate statistical tests were employed to ascertain their significance. Results: The study comprised 30 patients aged 30.77 ± 12.31 (mean ± SD) who presented at 12.29 ± 8.48 hours after consumption of yellow oleander. Vomiting (80%) was the most common presenting symptom. Metabolic abnormalities at presentation included hyperchloremia in 22 patients and metabolic acidosis (bicarbonate

Background: Previous studies have shown that chloride liberal fluids may be associated with worse renal outcomes. Deterioration of kidney function during hyperchloremia/chloride overload is believed to be induced by disturbances in renal perfusion, but exact mechanisms of chloride nephrotoxicity are unclear. The purpose of this randomized, crossover study was to investigate the effect of chloride loading on renal plasma flow (RPF), filtration fraction (FF) and glomerular filtration rate (GFR) in order to elucidate potential nephrotoxic mechanisms of chloride infusion. Methods: Fifteen healthy males were investigated twice after treatment with 2L isotonic saline and plasma-lyte with a wash-out period of at least 10 days. Within 15 mins after completion of infusion, the kidney parameters (RPF, FF and GFR) were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. Results: 99-mTc-DTPA renography showed reduction in both mean GFR (114 ± 13 ml/min vs.119 ± 12 ml/min, p = 0.04) and RPF (977 ± 272 ml/min vs. 1066 ± 197 ml/min, p = 0.19) and increasing FF (12% ± 2% vs. 11% ± 2%, p = 0.19) after 0.9% saline comparing to Plasmalyte, but only GFR reduction was statistically significant. Reduction in GFR and RPF and increasing in FF after 0.9% saline was observed in 10 subjects while in 5 others the reverse trend was shown. There were no statistically significant differences between mean systolic and diastolic blood pressure (BP) before and after each infusion except baseline diastolic BP. Weight changes (Δ weight) were similar after each infusion. Conclusions: We have demonstrated that high chloride infusion can affect kidney function in healthy subjects and seems to lead to impairment in both RPF and GFR.

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency in children. The capillary beta-hydroxybutyrate (BOHB) is increasingly used in the diagnosis and management of DKA. This study's objective is to assess the clinical and statistical correlation of BOHB with standard acidosis markers such as pH and HCO3. Materials and Methods: We retrospectively reviewed the electronic medical record of children aged 2 months to 16 years with DKA from January 2018 to January 2020 admitted in the pediatric intensive care unit of The Indus Hospital which is a tertiary care specialized center. All children received the treatment according to the standard protocol. Capillary blood BOHB was measured on admission, q 4–6 hourly, and blood glucose was also measured. All parameters were recorded on a structured sheet. Results: Among 1080 critically ill admissions, 26 patients (2.4%) were diagnosed as DKA. The mean age was 9.8 ± 3.8 years, and females were 54%. Half patients were newly diagnosed with Type 1-Insulin dependant diabetes mellitus (1DDM). Mild, moderate, and severe cases of DKA were 19%, 50%, and 31%, respectively. The median time to resolution of acidosis was 17 (10–39) h. At the time of resolution of acidosis, the correlation between capillary BOHB and blood pH (r = 0.11, P= 0.56), HCO3(r = 0.37, P = 0.86), AG (r = 0.37, P = 0.06), and base deficit (r = 0.04, P = 0.82) was noted. Hyperchloremia was present in 61.5% of cases. Five patients (19.2%) developed AKI that recovered. There was a strong clinical correlation of beta-hydroxybutyrate (BHOB) with standard acidosis markers of DKA management. Conclusion: Bedside capillary blood BOHB is a simple, inexpensive, point-of-care test that helps diagnose and treat DKA, especially in resource-limited settings, for avoiding unnecessary delays.

During pregnancy there are modifications in the metabolic profile of sheep that may predispose to the occurrence of metabolic disorders, of which pregnancy toxaemia (PT) is highlighted. Blood gas analysis is detects changes in acid-base and electrolyte balance effectively. The objectives of this study were to study the acid-base and electrolyte balance of sheep during gestation and in the immediate peripartum (up to 48 hours postpartum), comparing single gestation with twins. Sixty healthy sheep of Dorper breed, two to five years old were raised in a semi-intensive system and were divided in two experimental groups: Group 1: 30 ewes, with ultrasonographic diagnosis of single fetus gestation; Group 2: 30 ewes, with ultrasonographic diagnosis of twin pregnancy. The experimental moments were defined as: MI-immediately after artificial insemination (control); MG30 - 30 days of gestation; MG90 - 90 days of gestation; MG120 - 120 days of gestation; MG130 - 130 days of gestation; MG140 - 140 days of gestation; MP - lambing; MPP1 - 24h postpartum; MPP2 - 48h postpartum. At all times 1mL of blood was collected per jugular vein puncture for blood gas evaluation in a portable equipament (I-Stat®). The pH, carbon dioxide pressure (PCO2), bicarbonate (HCO3-), base excess (BE), sodium (Na+), potassium (K+), chloride (Cl-), ionized calcium (Ca+2), lactate, anion gap (AG) were mensured and strong ion difference (SID) were calculed. This work showed that there were changes in acid-base and electrolyte balance in pregnant ewes, due to the decrease in BE, HCO3-, TCO2 and increase of lactate and AG during gestation, but the pH remained normal and did not present any difference among moments in both groups. Comparing the groups, single-gestation ewes presented higher alkaline expenditure at delivery than twin-gestation, evidenced by lower levels of BE and HCO3-. Lower Na+ levels were observed in prepartum; drop in K+ values with advancing gestation; hyperchloremia and hypocalcemia during gestation according to the reference standards for species; decreased iCa+2 levels in the final third of gestation in both groups. It was concluded that the ewes of this study were healthy until the last moment analyzed (48h postpartum), although have shown greater consumption of the alkaline reserve in the peripartum, being more explicit in the single gestation animals. In addition, this situation can be physiological and result in increased energy demand during gestation, more exacerbated by peripartum. RESUMO: Durante a gestação ocorrem modificações metabólicas nas ovelhas que podem predispor a ocorrência de transtornos metabólicos, dos quais se destaca a toxemia da prenhez (TP). A hemogasometria é um exame que detecta alterações nos equilíbrios ácido-básico e eletrolítico de forma eficaz. Os objetivos deste estudo foram estudar os equilíbrios ácido-básico e eletrolítico de ovelhas durante a gestação e no periparto imediato (até 48 horas pós-parto), comparando-se gestação única com gemelar. Foram utilizadas 60 ovelhas criadas em manejo semi-intensivo, hígidas, da raça Dorper, com dois a cinco anos de idade. Foram constituídos dois grupos experimentais: Grupo 1: 30 ovelhas, com diagnóstico ultrassonográfico de gestação de feto único; Grupo 2: 30 ovelhas, com diagnóstico ultrassonográfico de gestação gemelar. Os momentos experimentais foram definidos como: MI - imediatamente após a inseminação artificial (controle); MG30 - 30 dias de gestação; MG90 - 90 dias de gestação; MG120 - 120 dias de gestação; MG130 - 130 dias de gestação; MG140 - 140 dias de gestação; MP - dia do parto; MPP1 - 24h pós-parto; MPP2 - 48h pós-parto. Em todos os momentos foi colhido 1mL de sangue por punção da veia jugular para avaliação hemogasométrica em aparelho portátil (I-Stat®). Foram analisados os parâmetros: pH, pressão de dióxido de carbono (PCO2), bicarbonato (HCO3-), excesso de bases (EB), sódio (Na+), potássio (K+), cloreto (Cl-), cálcio ionizado (iCa+2), lactato, ânion gap (AG) e diferença de íons fortes (SID). Este trabalho mostrou que houve mudanças nos equilíbrios ácido-básico e eletrolítico nas ovelhas prenhes, pela diminuição do EB, HCO3- e aumento do lactato e AG no decorrer da gestação, porém o pH se manteve dentro da normalidade e não apresentou diferença ao longo dos momentos em ambos os grupos. Comparando os grupos, as ovelhas de gestação única apresentaram maior consumo da reserva alcalina no momento do parto do que as de gestação gemelar, evidenciado menores níveis de EB e HCO3-. Foram observados níveis mais baixos de Na+ no pré-parto; queda dos valores de K+ com o avanço da gestação; hipercloremia e hipocalcemia durante a gestação segundo os padrões de referência para espécie e diminuição dos níveis de iCa+2 no terço final da gestação nas ovelhas de ambos os grupos. Concluiu-se que as ovelhas deste estudo apresentaram-se saudáveis até o último momento analisado (48h pós-parto), embora tenham mostrado maior consumo da reserva alcalina no periparto, sendo mais evidente nos animais de gestação única. Apesar disso, essa ocorrência pode ser considerada fisiológica e consequência do aumento da demanda energética durante a gestação, mais exacerbada no periparto.