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Trifi A, Ben Braik I, Galai H, Azzouz N, Tlili B, Mehdi A, Messaoud L, Seghir E, Ouhibi A, Abdellatif S. 0.9% sodium chloride versus ringer's lactate in the management of severe diabetic ketoacidosis: A randomized trial. Med Intensiva 2025:502203. [PMID: 40234173 DOI: 10.1016/j.medine.2025.502203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/27/2025] [Accepted: 03/12/2025] [Indexed: 04/17/2025]
Abstract
OBJECTIVE We aimed to compare the effect of 0.9% sodium chloride (SC) versus ringer's lactate (RL) in the resolution of diabetic ketoacidosis (DKA). DESIGN Open randomized trial. SETTING A medical ICU from November 2022 to September 2023. PATIENTS All patients older than 16 years admitted to the ICU for severe DKA. INTERVENTION The enrolled patient was assigned to receive RL or 0.9% SC according to the randomization scheme. Insulin therapy protocol was conducted similarly for all patients. MAIN VARIABLES OF INTEREST Resolution of DKA at H48 defined by a composite endpoint (glycemia < 11 mmol/l, bicarbonates > 15 mmol/l or pH > 7.30 and anion gap < 16), change in base excess, insulin needs, fluid administration volume, electrolytes (sodium, potassium, chloride), ICU length of stay, and 28-day mortality. RESULTS 88 patients were included: SC arm (n = 42) versus RL arm (n = 46). No significant differences were observed in diabetic ketoacidosis resolution, other variables of interest or in the subgroup analysis. The monitored biomarkers showed in the RL group: a better improvement of bicarbonate at H12 (p = 0.05), best potassium level both at H24 (p = 0.008) and H48 (0.041), lower chloride at H48 (p = 0.002) and higher glycemia at H24. CONCLUSION RL did not lead to faster resolution of diabetic ketoacidosis but decreased the risk of hyperchloremia and hypokalemia without increasingthe chance of hyperlactatemia. CLINICAL TRIAL REGISTRATION NUMBER NCT05808972.
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Affiliation(s)
- Ahlem Trifi
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia.
| | - Ikram Ben Braik
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Hounaida Galai
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Noussair Azzouz
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Badis Tlili
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Asma Mehdi
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Lynda Messaoud
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Eya Seghir
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Asma Ouhibi
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
| | - Sami Abdellatif
- Medical ICU, Teaching Hospital of la Rabta, Tunis, Tunisia; Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia
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Agarwal A, Jayashree M, Nallasamy K, Dayal D, Attri SV. 0.9% Saline versus Ringer's lactate as initial fluid in children with diabetic ketoacidosis: a double-blind randomized controlled trial. BMJ Open Diabetes Res Care 2025; 13:e004623. [PMID: 40194836 PMCID: PMC11977471 DOI: 10.1136/bmjdrc-2024-004623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 02/26/2025] [Indexed: 04/09/2025] Open
Abstract
INTRODUCTION Ringer's lactate (RL), a balanced crystalloid by regenerating bicarbonate ion, may lead to early diabetic ketoacidosis (DKA) resolution and reduced hyperchloremia as compared with 0.9% saline (NS). RESEARCH DESIGN AND METHODS This was a double-blind randomized controlled trial conducted in the pediatric emergency and intensive care units of a teaching hospital. Children with type 1 diabetes mellitus (T1DM) aged 9 months to 12 years who presented in DKA were included. Participants were randomized to receive either NS or RL as initial fluid (used for both resuscitation and replacement). The primary outcome was time to resolution of DKA. Secondary outcomes included change in serum chloride and bicarbonate from baseline, total fluid received and incidence of acute kidney injury. RESULTS The study was conducted between December 2020 and December 2021, and 67 children were recruited (34 in the NS group and 33 in the RL group). The mean time to DKA resolution was shorter in the RL group compared with the NS group (12.9±7.9 vs 16.8±9 hours). The mean difference and HR for time to DKA resolution in the RL group compared with the NS group were 3.85 hours (95% CI 0.3 to 8) and 1.39 hours (95% CI 1.25 to 1.56), respectively. The rise in chloride from baseline was higher in the NS group as compared with the RL group at 4 and 8 hours (8.7±5.6 vs 3.9±5.1 mmol/L) and (10.8±7.7 vs 4.4±8.3 mmol/L), respectively. On the contrary, the rise in bicarbonate from baseline to 12 hours was significantly higher in the RL group as compared with the NS group (14.7±1.6 vs 12.9±3.1). CONCLUSIONS The time to resolution of DKA was shorter in RL group as compared with the NS group. Regeneration of bicarbonate from lactate ion in the RL forms a strong physiological basis for this outcome as compared with hyperchloremia induced by NS. This makes RL a favorable option in children with DKA.
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Affiliation(s)
- Ashish Agarwal
- Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana, India
| | - Muralidharan Jayashree
- Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana, India
| | - Karthi Nallasamy
- Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana, India
| | - Devi Dayal
- Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana, India
| | - Savita Verma Attri
- Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana, India
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Bharti D, Selvam S, Sharma N, Dutta P, Pannu AK. Balanced crystalloid (Sterofundin) vs. normal saline for diabetic ketoacidosis: a prospective intervention trial with historical controls. QJM 2025; 118:79-86. [PMID: 39180713 DOI: 10.1093/qjmed/hcae169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/05/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND Fluid therapy with normal saline (NS) in diabetic ketoacidosis (DKA) can cause hyperchloremic acidosis and delay DKA resolution. Balanced crystalloids may address this concern, though results with Ringer lactate and Plasma-Lyte have been mixed. AIM This study aimed to compare the effectiveness of Sterofundin (SF) vs. NS in the management of DKA. METHODS A prospective, intervention trial with historical controls was conducted at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Patients aged 13 years or older with DKA were enrolled. The primary outcome was the time taken to DKA resolution, with a predefined superiority margin of a one-fourth reduction in resolution time. Secondary outcomes included total intravenous fluid and short-acting regular insulin requirements, the need for 0.45% saline, hospital stay duration and in-hospital mortality. RESULTS A total of 150 patients (mean age 36.8 years, 56.7% males) were included, with 75 receiving SF (intervention group) and 75 receiving NS (historical control group). The SF group showed a significantly shorter mean time to DKA resolution (13.8 ± 6.0 h) compared to the NS group (18.1 ± 5.5 h; P < 0.001). SF patients required less total intravenous fluid (4500 vs. 6000 ml; P = 0.004), less insulin (98 units vs. 112 units; P = 0.017) and had a lower need for 0.45% saline (8% vs. 74.3%; P < 0.001). Patients receiving SF had shorter hospital stays (4 [interquartile range, IQR 3-5] days vs. 4 [IQR 4-6] days; P = 0.020). Mortality rates were similar between the groups (SF: 9.3%, NS: 8.1%; P = 0.791). CONCLUSION SF may be a superior alternative to NS for fluid therapy in DKA.
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Affiliation(s)
- D Bharti
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India
| | - S Selvam
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India
| | - N Sharma
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India
| | - P Dutta
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Nehru Hospital Extension, Chandigarh 160012, India
| | - A K Pannu
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India
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Ghosh S. Intravenous Fluid Prescription in Diabetic Ketoacidosis: Where is the Evidence? Indian J Crit Care Med 2025; 29:10-11. [PMID: 39802242 PMCID: PMC11719552 DOI: 10.5005/jp-journals-10071-24875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025] Open
Abstract
How to cite this article Ghosh S. Intravenous Fluid Prescription in Diabetic Ketoacidosis: Where is the Evidence? Indian J Crit Care Med 2025;29(1):10-11.
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Affiliation(s)
- Supradip Ghosh
- Department of Critical Care Medicine, Max Super Speciality Hospital, Lucknow, Uttar Pradesh, India
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Tas N, Mengen E, Alacakır N, Goncu S, Boluk O, Ucakturk A. Is there a relationship between hyperchloremia status and the risk of developing acute kidney injury in pediatric patients with diabetic ketoacidosis? Eur J Pediatr 2024; 183:4319-4327. [PMID: 39080001 DOI: 10.1007/s00431-024-05697-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 07/16/2024] [Accepted: 07/18/2024] [Indexed: 09/20/2024]
Abstract
Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Prerenal acute kidney injury (AKI) is associated with profound hypovolemia and reduced renal perfusion. Results regarding hyperchloremia-associated AKI in patients with DKA are conflicting; we therefore investigated the potential relationship between hyperchloremia status and the risk of developing AKI. This single-center cohort study included 113 newly diagnosed T1DM patients with DKA admitted to the pediatric intensive care unit. Laboratory parameters, including Na, K, urea, creatinine, and chloride levels, were retrospectively reviewed at the time of presentation and at 12, 24 and 36 h. AKI was defined using the eGFR according to the pediatric RIFLE classification criteria. Twenty-two (19.5%) of the 113 patients were in the AKI group. Two-way repeated-measures ANOVA showed significant (P values ≤ 0.01) time interaction effects within the groups based on the eGFR and the serum chloride, hyperchloremia, and phosphate levels. Serum chloride levels did not differ between the groups during the first 12 h (p > 0.05) but were significantly greater in the AKI group than in the non-AKI group at 24 h and 36 h (p < 0.01). The final DKA resolution time was significantly greater in the AKI group than in the non-AKI group [22.2 (9.5) vs. 17.0 (12.0) h, respectively; p = 0.03]. However, the groups had similar lengths of hospital stay [13.0 (8.0) days vs. 12.0 (4.0) days, respectively; p = 0.17].Conclusions: Hyperchloremia may be iatrogenic rather than causative during treatment. This may worsen renal failure and prolong the recovery and treatment time for DKA patients. What is Known? • Acute kidney injury resulting from severe volume depletion is a common occurrence in diabetic ketoacidosis and typically requires significant volume replacement therapy. • In recent years, hyperchloremia has been associated with increased risks of AKI, morbidity, and mortality in some conditions, such as diabetic ketoacidosis. What is New? • The incidence of hyperchloremia increases over time during the treatment of diabetic ketoacidosis. • Hyperchloremia may be an iatrogenic element rather than a cause of acute kidney injury during the treatment of diabetic ketoacidosis.
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Affiliation(s)
- Nesrin Tas
- Department of Pediatric Nephrology, University of Health Sciences Ankara Training and Research Hospital, Ankara, Turkey.
- Ankara Eğitim Ve Araştırma Hastanesi Hacettepe, Mh. Ulucanlar Cd. No:89 Altındağ, Ankara, 06230, Turkey.
| | - Eda Mengen
- Department of Pediatric Endocrinology, University of Health Sciences Ankara Training and Research Hospital, Ankara, Turkey
| | - Nuri Alacakır
- Department of Pediatric Intensive Care Unit, University of Health Sciences Ankara Training and Research Hospital, Ankara, Turkey
| | - Sultan Goncu
- Department of Pediatric Intensive Care Unit, University of Health Sciences Ankara Training and Research Hospital, Ankara, Turkey
| | - Oguz Boluk
- Department of General Pediatrics, University of Health Sciences Ankara Training and Research Hospital, Ankara, Turkey
- Ankara Eğitim Ve Araştırma Hastanesi Hacettepe, Mh. Ulucanlar Cd. No:89 Altındağ, Ankara, 06230, Turkey
| | - Ahmet Ucakturk
- Department of Pediatric Endocrinology, University of Health Sciences Ankara Training and Research Hospital, Ankara, Turkey
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Singhal D, Gupta S, Kumar V. Normal Saline Versus Ringer's Lactate for Intravenous Fluid Therapy in Children with Diabetic Ketoacidosis: A Randomized Controlled Trial. Indian J Pediatr 2024:10.1007/s12098-024-05240-9. [PMID: 39302535 DOI: 10.1007/s12098-024-05240-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 08/06/2024] [Indexed: 09/22/2024]
Abstract
OBJECTIVES To compare normal saline (NS) and ringer's lactate (RL) as intravenous fluid therapy in children with diabetic ketoacidosis (DKA). METHODS This was a triple blinded randomized controlled trial conducted in the Pediatric Intensive Care Unit (PICU) of a tertiary care hospital in New Delhi from November 2018 to March 2020. The study compared intravenous fluid therapy with ringer's lactate and normal saline in children aged 6 mo to 18 y with DKA as defined by The International Society for Pediatric and Adolescent Diabetes (ISPAD). The primary objective was comparing the time taken to achieve resolution of acidosis (pH ≥ 7.3) in both groups. Secondary objectives included comparing the proportion of patients that develop acute kidney injury; comparing the time taken for normalization of anion gap and blood glucose; time taken to change the type of fluid; total amount of fluid and insulin administered; and total length of PICU and hospital stay. RESULTS Fifty patients were enrolled, with 25 in each arm and all but one achieved the primary outcome. The median age of the patients was 9 (5, 12) y. The time taken for resolution of acidosis in patients treated with NS was 12 (4, 18) h and with RL was 8 (4, 10) h (p = 0.16). The NS group had a significantly higher incidence of hyperchloremia (p < 0.05) and longer PICU stay (p < 0.05). The metabolic profile and incidence of complications were comparable in both groups. CONCLUSIONS Ringer's lactate can safely be considered for the management of pediatric DKA and may be preferred in patients that are at a risk of complications due to hyperchloremia.
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Affiliation(s)
- Devanshi Singhal
- Department of Pediatrics, Maulana Azad Medical College, and Associated Hospitals, New Delhi, India
| | - Shalu Gupta
- Division of Pediatric Critical Care, Department of Pediatrics, Lady Hardinge Medical College, and Kalawati Saran Children's Hospital, New Delhi, India.
| | - Virendra Kumar
- Department of Pediatrics, Maulana Azad Medical College, and Associated Hospitals, New Delhi, India
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Jamison A, Mohamed A, Chedester C, Klindworth K, Hamarshi M, Sembroski E. Lactated Ringer's versus normal saline in the management of acute diabetic ketoacidosis (RINSE-DKA). Pharmacotherapy 2024; 44:623-630. [PMID: 39077895 DOI: 10.1002/phar.4600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 05/28/2024] [Accepted: 06/02/2024] [Indexed: 07/31/2024]
Abstract
INTRODUCTION A mainstay in the acute management of diabetic ketoacidosis (DKA) is fluid resuscitation. Normal saline is recommended by the American Diabetes Association; however, it has been associated with hyperchloremic metabolic acidosis and acute kidney injury. Limited literature is available to determine the most appropriate crystalloid fluid to treat patients with DKA. OBJECTIVE The purpose of this study was to compare lactated Ringer's (LR) to normal saline (NS) in the acute management of DKA. METHODS This was a retrospective, multicenter single health system cohort study. The primary outcome was to evaluate the time to high anion gap metabolic acidosis (HAGMA) resolution using LR compared to NS. Secondary outcomes included the incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy. Other secondary outcomes included insulin infusion duration and hospital and intensive care unit length of stay. The Cox proportional hazards model was used for the primary outcome. RESULTS A total of 771 patient encounters were included. Lactated Ringer's was associated with faster time to HAGMA resolution compared to NS (adjusted hazard ratio 1.325; 95% confidence interval 1.121-1.566; p < 0.001). No difference was found in complications such as incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy between the LR and NS groups. Additionally, there was no difference in insulin infusion duration and hospital or intensive care unit length of stay. CONCLUSION Treatment with LR as the primary crystalloid for acute DKA management was associated with faster HAGMA resolution compared with NS. Similar incidence in complications and length of stay was observed between the two groups. The findings of this study add to the accumulating literature suggesting that balanced crystalloids may offer an advantage over NS for the treatment of patients with DKA.
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Affiliation(s)
- Auriene Jamison
- Saint Luke's Hospital of Kansas City, Kansas City, Missouri, USA
| | - Adham Mohamed
- Saint Luke's Hospital of Kansas City, Kansas City, Missouri, USA
| | | | - Kyle Klindworth
- Saint Luke's Hospital of Kansas City, Kansas City, Missouri, USA
| | - Majdi Hamarshi
- Saint Luke's Hospital of Kansas City, Kansas City, Missouri, USA
| | - Erik Sembroski
- Saint Luke's Hospital of Kansas City, Kansas City, Missouri, USA
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Szabó GV, Szigetváry C, Turan C, Engh MA, Terebessy T, Fazekas A, Farkas N, Hegyi P, Molnár Z. Fluid resuscitation with balanced electrolyte solutions results in faster resolution of diabetic ketoacidosis than with 0.9% saline in adults - A systematic review and meta-analysis. Diabetes Metab Res Rev 2024; 40:e3831. [PMID: 38925619 DOI: 10.1002/dmrr.3831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 02/12/2024] [Accepted: 05/31/2024] [Indexed: 06/28/2024]
Abstract
Fluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline-group) was compared to BES (BES-group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of -5.36 [95% CI: -10.46, -0.26] hours. Post-resuscitation chloride (MD: -4.26 [-6.97, -1.54] mmoL/L) and sodium (MD: -1.38 [-2.14, -0.62] mmoL/L) levels were significantly lower. In contrast, levels of post-resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES-group compared to the Saline-group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [-3.03, 3.35] hours) or mortality (OR: -0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta-analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation.
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Affiliation(s)
- Gergő Vilmos Szabó
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Emergency Department, Szent György University Teaching Hospital of Fejér County, Székesfehérvár, Hungary
- National Ambulance Service, Budapest, Hungary
- Hungarian Air Ambulance Nonprofit Ltd., Budaörs, Hungary
| | - Csenge Szigetváry
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary
| | - Caner Turan
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary
| | - Marie Anne Engh
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Tamás Terebessy
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Orthopaedics, Semmelweis University, Budapest, Hungary
| | - Alíz Fazekas
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Nelli Farkas
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Zsolt Molnár
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary
- Department of Anesthesiology and Intensive Therapy, Poznan University, Poznan, Poland
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Johnson J, Drincic A, Buddenhagen E, Nein K, Samson K, Langenhan T. Evaluation of a Protocol Change Promoting Lactated Ringers Over Normal Saline in the Treatment of Diabetic Ketoacidosis. J Diabetes Sci Technol 2024; 18:549-555. [PMID: 38454546 PMCID: PMC11089871 DOI: 10.1177/19322968241235941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/09/2024]
Abstract
BACKGROUND Current guidelines recommend normal saline (NS) for fluid resuscitation in the management of patients presenting with diabetic ketoacidosis (DKA). However, previous prospective studies have demonstrated improvement in patient-specific outcomes, including time to DKA resolution, when balanced crystalloid fluids are used. METHODS We conducted a single institution, retrospective cohort study of adult patients admitted with DKA before and after a protocol change within our institution, which shifted the default resuscitative and maintenance fluid in our DKA management protocol from NS to lactated Ringer's solution (LR). The primary outcome was time from DKA clinical presentation until DKA resolution. The secondary outcome was time to discontinuation of DKA protocol insulin drip. RESULTS Of 246 patients meeting inclusion criteria, 119 were in the NS group (preprotocol change, where NS was the default resuscitative fluid) and 127 to the LR group (postprotocol change, where LR was the default resuscitative fluid). Time to DKA resolution was significantly decreased in the LR group (mean = 17.1 hours; standard deviation [SD] = 11.0) relative to the NS group (mean = 20.6 hours; SD = 12.2; P = .02). Duration of DKA protocol insulin drip was shorter in the LR group (mean = 16.0 hours; SD = 8.7) compared with the NS group (mean = 21.4 hours; SD = 12.5; P < .001). CONCLUSIONS In this retrospective cohort study, protocolized DKA intravenous fluid management with LR resulted in shorter time to resolution of DKA and reduced duration of DKA protocol insulin drip.
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Affiliation(s)
- Jake Johnson
- Division of Diabetes, Endocrine, and
Metabolism, Department of Internal Medicine, University of Nebraska Medical Center,
Omaha, NE, USA
| | - Andjela Drincic
- Division of Diabetes, Endocrine, and
Metabolism, Department of Internal Medicine, University of Nebraska Medical Center,
Omaha, NE, USA
| | - Emma Buddenhagen
- College of Medicine, University of
Nebraska Medical Center, Omaha, NE, USA
| | - Kaitlyn Nein
- College of Medicine, University of
Nebraska Medical Center, Omaha, NE, USA
| | - Kaeli Samson
- Department of Biostatistics, University
of Nebraska Medical Center, Omaha, NE, USA
| | - Trek Langenhan
- Division of Hospital Medicine,
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE,
USA
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Gilchrist HE, Hatton CJ, Roginski MA, Esteves AM. Impact on Diabetic Ketoacidosis Resolution After Implementation of a 2-Bag Fluid Order Set. Ann Pharmacother 2023; 57:1361-1366. [PMID: 37021360 DOI: 10.1177/10600280231163838] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023] Open
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is a serious acute complication of both type 1 and type 2 diabetes that requires prompt management. Limited data exist supporting the use of a 2-bag DKA protocol in adult patients across all levels of care. OBJECTIVE To evaluate the efficacy and safety of a 2-bag DKA protocol in comparison with a traditional DKA management strategy. METHODS Retrospective review of patients admitted with DKA between January 1, 2021, and February 28, 2022, at a single center. Patients were separated into 2 cohorts, traditional or 2-bag. The primary outcome was time to anion gap closure and/or beta-hydroxybutyrate normalization. Secondary outcomes include length of hospitalization, insulin infusion time, and hypoglycemic events. RESULTS One hundred forty-three patients had a DKA order set initiated during their admission, 59 in the traditional cohort and 84 in the 2-bag cohort. Mean time to anion gap closure was shorter in the 2-bag cohort (12.7 vs 16.9 hours; P = 0.005) and beta-hydroxybutyrate normalization (15.6 vs 25.6 hours; P = 0.026). No difference in hospital length of stay (4 vs 6 days; P = 0.113), duration of insulin infusion (41.6 vs 40.6 hours; P = 0.455), or rates of hypoglycemia (6 vs 4; P = 0.872) was seen. CONCLUSION AND RELEVANCE Implementation of a 2-bag DKA protocol in the inpatient setting was associated with a shorter time to anion gap closure and beta-hydroxybutyrate normalization. These findings support the option of expansion of a 2-bag DKA protocol to adult patients across all levels of care irrespective of the admission diagnosis.
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Affiliation(s)
- Hannah E Gilchrist
- Department of Pharmacy, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Colman J Hatton
- Section of Pulmonary and Critical Care Medicine, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Matthew A Roginski
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
- Department of Emergency Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Alyson M Esteves
- Department of Pharmacy, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
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11
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Woo JH, Lim YS, Cho JS, Yang HJ, Jang JH, Choi JY, Choi WS. Saline versus Plasma Solution-A in Initial Resuscitation of Patients with Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. J Clin Med 2023; 12:5040. [PMID: 37568442 PMCID: PMC10420180 DOI: 10.3390/jcm12155040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/10/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Although saline is commonly used during cardiopulmonary resuscitation (CPR) or post-cardiac arrest care, it has detrimental effects. This trial aimed to evaluate the efficacy of a balanced crystalloid solution (Plasma Solution-A [PS]) in out-of-hospital cardiac arrest (OHCA) patients and compare it with the efficacy of saline. METHODS A randomized, unblinded clinical trial was conducted using PS and saline for intravenous fluid administration during CPR and post-cardiac arrest care of non-traumatic OHCA patients admitted to the emergency department of a tertiary university hospital. Patients received saline (saline group) or PS (PS group) within 24 h of hospital arrival. The primary outcomes were changes in arterial pH, bicarbonate, base excess (BE), and chloride levels within 24 h. The secondary outcomes were clinical outcomes including mortality. RESULTS Of the 364 patients, data from 27 and 26 patients in the saline and PS groups, respectively, were analyzed. Analysis using a linear mixed model revealed a significant difference in BE change over time between the groups (treatment-by-time p = 0.044). Increase in BE and bicarbonate levels from 30 min to 2 h was significantly greater (p = 0.044 and p = 0.024, respectively) and the incidence of hyperchloremia was lower (p < 0.001) in the PS group than in the saline group. However, there was no difference in clinical outcomes. CONCLUSION Use of PS for resuscitation resulted in a faster improvement in BE and bicarbonate, especially in the early phase of post-cardiac arrest care, and lower hyperchloremia incidence than the use of saline, without differences in clinical outcomes, in OHCA patients.
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Affiliation(s)
| | - Yong Su Lim
- Department of Emergency and Critical Care Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea; (J.-H.W.)
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12
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Patlolla SR, Devara J, Ameer MA, Patlolla PR, Ponnala M. Euglycemic Diabetic Ketoacidosis in a Patient With Urinary Tract Infection. Cureus 2023; 15:e42594. [PMID: 37641775 PMCID: PMC10460495 DOI: 10.7759/cureus.42594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2023] [Indexed: 08/31/2023] Open
Abstract
Diabetes Mellitus (DM) is a complex metabolic disease primarily associated with elevated blood glucose levels in the body. Diabetic ketoacidosis (DKA) is the most feared acute presentation of diabetes mellitus (DM) in both type 1 and type 2 diabetes mellitus. Furthermore, euglycemic diabetic ketoacidosis (EDKA) is a relatively rare complication of DM in which the blood glucose levels are usually less than 250 mg/dl with an elevated anion gap metabolic acidosis. It can be a diagnostic challenge due to normal blood glucose levels and often can be overlooked. Physicians should be aware of EDKA; prompt diagnosis and treatment are critical in the timely management of the condition to prevent complications. We present a case of EDKA in a 74-year-old female precipitated by a urinary tract infection which was identified and treated promptly with insulin and dextrose infusion. In addition to that, an important difference between British and American guidelines has been highlighted.
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13
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Tamzil R, Yaacob N, Noor NM, Baharuddin KA. Comparing the clinical effects of balanced electrolyte solutions versus normal saline in managing diabetic ketoacidosis: A systematic review and meta-analyses. Turk J Emerg Med 2023; 23:131-138. [PMID: 37529790 PMCID: PMC10389098 DOI: 10.4103/tjem.tjem_355_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 03/15/2023] [Accepted: 03/16/2023] [Indexed: 08/03/2023] Open
Abstract
The first-line treatment of diabetes ketoacidosis (DKA) involves fluid resuscitation with normal saline infusion to correct hypovolemia. Hyperchloremic metabolic acidosis from aggressive normal saline administration was associated with worse clinical outcomes in managing DKA. Other choices for normal saline include balanced electrolyte solutions (BESs). This study aimed to compare the clinical effects between BESs and normal saline in managing DKA. This study was a systematic review of probing articles published from inception to October 2021 in Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Google Scholar, and Scopus. Eight randomized controlled trials with a total of 595 individuals were included. The data were analyzed at 95% confidence level using random-effects models. For the primary outcomes, there was no difference in the duration of DKA resolution. (Mean difference [MD] -4.73, 95% confidence interval [CI] -2.72-4.92; I2 = 92%; P = 0.180). However, there was a significantly lower postresuscitation chloride concentration in the BES (MD 2.96 95% CI - 4.86 to - 1.06; I2 = 59%; P = 0.002). For the secondary outcomes, there was a significant reduction in duration for normalization of bicarbonate in the BES group (MD 3.11 95% CI - 3.98-2.23; I2 = 5%; P = 0.0004). There were no significant differences between groups in duration for recovery of pH, intensive unit admission, and adverse events (mortality and acute renal failure). Resuscitation with BES was associated with decreased chloride and increased bicarbonate values in DKA patients. It suggests that BES prevents DKA patients from hyperchloremic metabolic acidosis.
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Affiliation(s)
- Rozinadya Tamzil
- Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Normalinda Yaacob
- Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Norhayati Mohd Noor
- Department of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Kamarul Aryffin Baharuddin
- Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
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14
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Othman MI, Nashwan AJ, Alfayoumi M, Khatib M, Abujaber AA. Plasma-Lyte-148 Versus Normal Saline 0.9% in Diabetic Ketoacidosis Management: A Review. Cureus 2023; 15:e41079. [PMID: 37519584 PMCID: PMC10375921 DOI: 10.7759/cureus.41079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2023] [Indexed: 08/01/2023] Open
Abstract
Diabetic ketoacidosis (DKA) is a critical complication of diabetes mellitus characterized by hyperglycemia, ketonemia, circulatory collapse, hypokalemia, and metabolic acidosis. The therapeutic management of DKA includes vigilant fluid resuscitation to address dehydration and electrolyte imbalances and restore hemodynamic stability. The choice of fluid, either isotonic saline or a balanced electrolyte solution like Plasma-Lyte 148 (PL), is pivotal in the clinical outcomes of DKA patients. Recent studies have compared the effectiveness of these fluid solutions in DKA management, focusing on different clinical outcomes such as the resolution of metabolic acidosis, electrolyte imbalances, the incidence of acute kidney injury, and length of hospital stay. This review examines the literature comparing isotonic saline and balanced electrolyte solutions for fluid resuscitation in DKA, analyzing the associated clinical outcomes. Through synthesizing research findings, this review aims to elucidate the efficacy and potential advantages of utilizing PL as an alternative to traditional isotonic saline for fluid resuscitation in treating DKA. This would further facilitate evidence-based decision-making among healthcare professionals and contribute to optimizing DKA management strategies. Understanding the intricacies and implications of fluid resuscitation is crucial, given its profound impact on patient outcomes in DKA management.
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15
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Gripp KE, Trottier ED, Thakore S, Sniderman J, Lawrence S. Current recommendations for management of paediatric diabetic ketoacidosis. Paediatr Child Health 2023; 28:128-138. [PMID: 37151932 PMCID: PMC10156932 DOI: 10.1093/pch/pxac119] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 06/20/2022] [Indexed: 05/09/2023] Open
Abstract
Treatment of paediatric diabetic ketoacidosis (DKA) includes careful attention to fluids and electrolytes to minimize the risk of complications such as cerebral injury (CI), which is associated with high morbidity and mortality. The incidence of cerebral edema in paediatric DKA has not decreased despite the use of fluid-limiting protocols based on restricting early fluid resuscitation. New evidence suggests that early isotonic fluid therapy does not confer additional risk and may improve outcomes in some patients. Protocols and clinical practice guidelines are being adjusted, with a particular focus on recommendations for initial and ongoing fluids and electrolyte monitoring and replacement. Initial isotonic fluid resuscitation is now recommended for all patients in the first 20 to 30 minutes after presentation, followed by repletion of volume deficit over 36 hours in association with an insulin infusion, electrolyte supplementation, and careful monitoring for and management of potential CI.
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Affiliation(s)
- Karen E Gripp
- Canadian Paediatric Society, Acute Care Committee, Ottawa, Ontario, Canada
| | - Evelyne D Trottier
- Canadian Paediatric Society, Acute Care Committee, Ottawa, Ontario, Canada
| | - Sidd Thakore
- Canadian Paediatric Society, Acute Care Committee, Ottawa, Ontario, Canada
| | - Jonathan Sniderman
- Canadian Paediatric Society, Acute Care Committee, Ottawa, Ontario, Canada
| | - Sarah Lawrence
- Canadian Paediatric Society, Acute Care Committee, Ottawa, Ontario, Canada
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16
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Gripp KE, Trottier ED, Thakore S, Sniderman J, Lawrence S. Les recommandations en vigueur pour la prise en charge de l'acidocétose diabétique pédiatrique. Paediatr Child Health 2023; 28:128-138. [PMID: 37151921 PMCID: PMC10156930 DOI: 10.1093/pch/pxac120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 06/20/2022] [Indexed: 05/09/2023] Open
Abstract
Pour traiter l'acidocétose diabétique pédiatrique, il faut porter une attention particulière aux liquides et aux électrolytes pour limiter le risque de complications, telles qu'une lésion cérébrale, associée à une morbidité et une mortalité élevées. L'incidence d'œdème cérébral en cas d'acidocétose diabétique n'a pas diminué malgré les protocoles visant la limitation des liquides qui s'appuient sur la restriction de la réanimation liquidienne initiale. Selon de nouvelles données probantes, l'administration précoce de liquides isotoniques n'entraîne pas de risque supplémentaire et peut améliorer les résultats cliniques chez certains patients. Les protocoles et les directives cliniques sont adaptés et axés particulièrement sur la surveillance et le remplacement initiaux et continus des liquides et des électrolytes. Il est maintenant recommandé de commencer par une réanimation à l'aide de liquides isotoniques chez tous les patients dans les 20 à 30 minutes suivant leur arrivée à l'hôpital, suivie par la réplétion du déficit volumique sur une période de 36 heures, en association avec une perfusion d'insuline et des suppléments d'électrolytes, ainsi qu'avec la surveillance et la prise en charge attentives d'une éventuelle lésion cérébrale.
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Affiliation(s)
- Karen E Gripp
- Société canadienne de pédiatrie, comité des soins aigus, Ottawa (Ontario)Canada
| | - Evelyne D Trottier
- Société canadienne de pédiatrie, comité des soins aigus, Ottawa (Ontario)Canada
| | - Sidd Thakore
- Société canadienne de pédiatrie, comité des soins aigus, Ottawa (Ontario)Canada
| | - Jonathan Sniderman
- Société canadienne de pédiatrie, comité des soins aigus, Ottawa (Ontario)Canada
| | - Sarah Lawrence
- Société canadienne de pédiatrie, comité des soins aigus, Ottawa (Ontario)Canada
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17
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Panchal V, Sivasubramanian BP, Samala Venkata V. Crystalloid Solutions in Hospital: A Review of Existing Literature. Cureus 2023; 15:e39411. [PMID: 37362468 PMCID: PMC10287545 DOI: 10.7759/cureus.39411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2023] [Indexed: 06/28/2023] Open
Abstract
Intravenous fluids (IVF) like normal saline (NS) and Ringer's lactate (RL) are often crucial in the management of hospitalized patients. Mishandling these fluids can lead to complications in about 20% of patients receiving them. In this review, we present the current evidence through the identification of observational studies and randomized trials that observed the optimal use of IVF. We found that NS may cause hyperchloremic metabolic acidosis in surgical patients, but there is no clear difference in mortality and long-term outcomes between NS and balanced crystalloids. Critically ill patients, particularly those in sepsis, benefit from balanced crystalloids, as high chloride content fluids like NS increase the risk of complications and mortality. In pancreatitis, NS has been shown to increase the risk of ICU admission when compared to RL; however, there is no significant difference in long-term outcomes and mortality between the fluids. RL is preferred for burns due to its isotonicity and lack of protein, preventing edema formation in an already dehydrated state. Plasma-lyte may resolve diabetic ketoacidosis faster, while prolonged NS use can lead to metabolic acidosis, acute kidney injury, and cerebral edema. In conclusion, NS, RL, and plasma-lyte are the most commonly used isotonic IVF in the hospital population. Incorrect choice of fluids in a different clinical scenario can lead to worse outcomes.
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Affiliation(s)
- Viraj Panchal
- Medicine, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Barath Prashanth Sivasubramanian
- Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, USA
- Internal Medicine, ESIC Medical College & PGIMSR, Chennai, IND
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18
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Plasma volume expansion reveals hidden metabolic acidosis in patients with diabetic ketoacidosis. Intensive Care Med Exp 2022; 10:36. [PMID: 36038699 PMCID: PMC9424448 DOI: 10.1186/s40635-022-00464-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 08/13/2022] [Indexed: 11/30/2022] Open
Abstract
Background Hyperchloremic metabolic acidosis that develops during the treatment of diabetic ketoacidosis is usually attributed to the chloride content of resuscitation fluids. We explored an alternative explanation, namely that fluid-induced plasma volume expansion alters the absolute differences in the concentrations of sodium and chloride (the Na–Cl gap) enough to affect the acid–base balance. We analyzed data from a prospective single-center cohort study of 14 patients treated for diabetic ketoacidosis. All patients received 1 L of 0.9% saline over 30 min on two consecutive days. Blood gases were sampled before and after the infusions. Results The initial plasma volume was estimated to be 25 ± 13% (mean ± SD) below normal on admission to the intensive care unit. At that time, most patients had an increased actual Na–Cl gap, which counteracts acidosis. However, the correction of the plasma volume deficit revealed that these patients would have had a decreased Na–Cl gap upon admission if they had been normovolemic at that time; the estimated “virtual Na–Cl gap” of 29 ± 5 mmol/L was significantly lower than the uncorrected value, which was 39 ± 5 mmol/L (P < 0.001). On Day 2, most patients had a decreased actual Na–Cl gap (33 ± 5 mmol/L), approaching the corrected value on Day 1. Conclusions The hyperchloremic acidosis commonly seen in diabetic ketoacidosis may not be primarily caused by the chloride content of resuscitation fluids but, rather, by the restoration of plasma volume, which reveals the hidden metabolic acidosis caused by a decreased Na–Cl gap. Trial registration Clinical Trials Identifier NCT02172092, registered June 24, 2014, https://www.clinicaltrials.gov/NCT02172092 Supplementary Information The online version contains supplementary material available at 10.1186/s40635-022-00464-5.
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19
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Glaser N, Fritsch M, Priyambada L, Rewers A, Cherubini V, Estrada S, Wolfsdorf JI, Codner E. ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes 2022; 23:835-856. [PMID: 36250645 DOI: 10.1111/pedi.13406] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 01/01/2023] Open
Affiliation(s)
- Nicole Glaser
- Department of Pediatrics, Section of Endocrinology, University of California, Davis School of Medicine, Sacramento, California, USA
| | - Maria Fritsch
- Department of Pediatric and Adolescent Medicine, Division of General Pediatrics, Medical University of Graz, Austria Medical University of Graz, Graz, Austria
| | - Leena Priyambada
- Division of Pediatric Endocrinology, Rainbow Children's Hospital, Hyderabad, India
| | - Arleta Rewers
- Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado, USA
| | - Valentino Cherubini
- Department of Women's and Children's Health, G. Salesi Hospital, Ancona, Italy
| | - Sylvia Estrada
- Department of Pediatrics, Division of Endocrinology and Metabolism, University of the Philippines, College of Medicine, Manila, Philippines
| | - Joseph I Wolfsdorf
- Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Ethel Codner
- Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile
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20
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Carr JR, Hawkins WA, Newsome AS, Smith SE, Clemmons AB, Bland CM, Branan TN. Fluid Stewardship of Maintenance Intravenous Fluids. J Pharm Pract 2022; 35:769-782. [PMID: 33827313 PMCID: PMC8497650 DOI: 10.1177/08971900211008261] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Despite the frequent use of maintenance intravenous fluids (mIVF) in critically ill patients, limited guidance is available. Notably, fluid overload secondary to mIVF mismanagement is associated with significant adverse patient outcomes. The Four Rights (right drug, right dose, right duration, right patient) construct of fluid stewardship has been proposed for the safe evaluation and use of fluids. The purpose of this evidence-based review is to offer practical insights for the clinician regarding mIVF selection, dosing, and duration in line with the Four Rights of Fluid Stewardship.
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Affiliation(s)
- John R. Carr
- Department of Pharmacy, St. Joseph’s/Candler Health System, Savannah, GA, USA
| | - W. Anthony Hawkins
- Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Albany, GA, USA
- Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Albany, GA, USA
| | - Andrea Sikora Newsome
- Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Augusta, GA, USA
- Department of Pharmacy, Augusta University Medical Center, Augusta, GA, USA
| | - Susan E. Smith
- Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Athens, GA, USA
| | - Amber B Clemmons
- Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Augusta, GA, USA
- Department of Pharmacy, Augusta University Medical Center, Augusta, GA, USA
| | - Christopher M. Bland
- Department of Pharmacy, St. Joseph’s/Candler Health System, Savannah, GA, USA
- Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Savannah, GA, USA
| | - Trisha N. Branan
- Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Athens, GA, USA
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21
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The relationship between hyperchloremia and acute kidney injury in pediatric diabetic ketoacidosis and its impact on clinical outcomes. Pediatr Nephrol 2022; 37:1407-1413. [PMID: 34738144 DOI: 10.1007/s00467-021-05279-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 09/03/2021] [Accepted: 09/03/2021] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Diabetic ketoacidosis (DKA) is characterized by hyperglycemia, ketogenesis, and increased anion gap metabolic acidosis. Such derangements are accompanied by volume depletion as well as electrolyte disturbances. Resuscitation using traditional saline in DKA patients can exacerbate electrolyte abnormalities, in particular the production of hyperchloremia. Severe hypovolemia can result in acute kidney injury (AKI). The link between hyperchloremia and AKI is controversial. This study aimed to assess the relationship between hyperchloremia and AKI in pediatric patients with DKA and its impacts on clinical outcomes. METHODS This cross-sectional study was conducted on 70 children with DKA admitted to the pediatric intensive care unit in which all patients were subjected to detailed medical history taking and full clinical examination. Daily assessment of Na, K, urea, creatinine, chloride, arterial blood gases, and albumin/creatinine ratio (ACR) was done. AKI was defined as pRIFLE stage I and F. RESULTS Hyperchloremia was detected in 65.7% of patients at admission and in 52.9% after 24 h (p = 0.17). AKI was documented in 28% of patients. At admission hyperchloremia was detected in 56% of patients without AKI versus 90% of patients with AKI (p = 0.007). After 24 h, hyperchloremia was detected in 48.4% patients without versus 100% of patients with AKI. Chloride was significantly positively correlated to duration of admission, creatinine, ACR, and negatively correlated to eGFR. CONCLUSION The development of AKI in patients with DKA was accompanied by hyperchloremia, increased time to DKA resolution, and longer hospital stay. A higher resolution version of the Graphical abstract is available as Supplementary information.
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22
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Saline Compared to Balanced Crystalloid in Patients With Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Explor 2022; 4:e0613. [PMID: 35018349 PMCID: PMC8740878 DOI: 10.1097/cce.0000000000000613] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVES This systematic review and meta-analysis compared the use of saline to balanced crystalloid for fluid resuscitation in patients with diabetic ketoacidosis (DKA). DATA SOURCES We searched databases including Medline, Embase, and the Cochrane registry. STUDY SELECTION We included randomized controlled trials (RCTs) that compared saline to balanced crystalloid in patients with DKA. DATA EXTRACTION We pooled estimates of effect using relative risk for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% CIs. We assessed risk of bias for included RCTs using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluation methodology. DATA SYNTHESIS We included eight RCTs (n = 482 patients). Both time to DKA resolution (MD, 3.51 hr longer; 95% CI, 0.90 longer to 6.12 longer; moderate certainty) and length of hospital stay (MD, 0.89 d longer in saline group; 95% CI, 0.34 longer to 1.43 d longer; moderate certainty) are probably longer in the saline group compared with the balanced crystalloid group, although for the latter, the absolute difference (under 1 d) is small. Post-resuscitation serum chloride level may be higher (MD, 1.62 mmol/L higher; 95% CI, 0.40 lower to 3.64 higher; low certainty), and post-resuscitation serum bicarbonate is probably lower (MD, 1.50 mmol/L; 95% CI, 2.33 lower to 0.67 lower; moderate certainty) in those receiving saline. CONCLUSIONS In patients with DKA, the use of saline may be associated with longer time to DKA resolution, higher post-resuscitation serum chloride levels, lower post-resuscitation serum bicarbonate levels, and longer hospital stay compared with balanced crystalloids. Pending further data, low to moderate certainty data support using balanced crystalloid over saline for fluid resuscitation in patients with DKA.
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23
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Besen BAMP, Boer W, Honore PM. Fluid management in diabetic ketoacidosis: new tricks for old dogs? Intensive Care Med 2021; 47:1312-1314. [PMID: 34608527 DOI: 10.1007/s00134-021-06527-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 09/03/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Bruno Adler Maccagnan Pinheiro Besen
- Medical ICU, Disciplina de Emergências Clínicas, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
- Intensive Care Unit, Hospital A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
| | - Willem Boer
- Intensive Care Department, Ziekenhuis Oost Limburgh, Campus St Jan, Genk, Belgium
| | - Patrick M Honore
- Co-Director at the Intensive Care Dept of Brugmann University Hospital, Brussels, Belgium
- Faculty of Medicine, Professor at the ULB University, Brussels, Belgium
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24
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Hasim N, Bakar MAA, Islam MA. Efficacy and Safety of Isotonic and Hypotonic Intravenous Maintenance Fluids in Hospitalised Children: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. CHILDREN-BASEL 2021; 8:children8090785. [PMID: 34572217 PMCID: PMC8471545 DOI: 10.3390/children8090785] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/03/2021] [Accepted: 09/07/2021] [Indexed: 01/21/2023]
Abstract
Hyponatraemia is a known complication in hospitalised children receiving maintenance intravenous fluid. Several studies have been published to investigate the efficacy and safety of intravenous fluids in children. However, there is still an ongoing debate regarding the ideal solution to be used in the paediatric population. Therefore, the aim of this meta-analysis was to investigate the safety and efficacy of administering isotonic versus hypotonic intravenous maintenance fluid in hospitalised children. An extensive search was undertaken on PubMed, Web of Science, Scopus, ScienceDirect, Google Scholar and Cochrane Library on 28 December 2020. Only randomised controlled trials (RCTs) were included. We used the random-effects model for all analyses. Risk ratio (RR) and mean difference with 95% confidence intervals (CIs) were used for dichotomous and continuous outcomes, respectively. The quality of each study was assessed using the Joanna Briggs Institute critical appraisal tool for RCTs. This study is registered with PROSPERO (CRD42021229067). Twenty-two RCTs with a total of 3795 participants were included. The studies encompassed surgical and medical patients admitted to intensive care unit as well as to general wards. We found that hypotonic fluid significantly increases the risk of hyponatremia at both ≤24 h (RR 0.34; 95% CI: 0.26–0.43, p < 0.00001) and >24 h (RR 0.48; 95% CI: 0.36–0.64, p < 0.00001). Isotonic fluid increases the risk of hypernatraemia at ≤24 h (RR 2.15; 95% CI: 1.24–3.73, p = 0.006). The prevalence of hyponatraemia was also higher in the hypotonic group at both ≤24 h (5.7% vs. 23.3%) and >24 h (6.0% vs. 26.3%). There was no statistically significant difference in the risk of developing adverse outcomes between the two groups. Mean serum and urine sodium as well as serum osmolality/osmolarity was lower in the hypotonic group. Isotonic solution is protective against the development of hyponatraemia while hypotonic solution increases the risk of hyponatraemia.
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Affiliation(s)
- Norfarahin Hasim
- Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia;
- Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Mimi Azliha Abu Bakar
- Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia;
- Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
- Correspondence: (M.A.A.B.); or (M.A.I.)
| | - Md Asiful Islam
- Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
- Correspondence: (M.A.A.B.); or (M.A.I.)
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Abstract
Shock from all causes carries a high mortality. Rapid and intentional intervention to resuscitate can reduce mortality and organ injury. Approaches to fluid resuscitation, vasopressor use as well as commonly assessed laboratory values are reviewed in this paper.
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Bergmann KR, Abuzzahab MJ, Nowak J, Arms J, Cutler G, Christensen E, Finch M, Kharbanda A. Resuscitation With Ringer's Lactate Compared With Normal Saline for Pediatric Diabetic Ketoacidosis. Pediatr Emerg Care 2021; 37:e236-e242. [PMID: 30020245 DOI: 10.1097/pec.0000000000001550] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE The aims of this study were to describe the use of Ringer's lactate (LR) or normal saline (NS) for resuscitation among children with diabetic ketoacidosis (DKA) and compare the effect of fluid type on cost, length of stay, and rate of cerebral edema (CE). METHODS This is a retrospective study of 49,737 children aged 0 to 17 years with DKA between January 1, 2005, and September 30, 2015, using data from the Pediatric Health Information System. Treatment with LR or NS was identified. Our primary outcomes were total adjusted cost and length of stay. Our secondary outcome was CE rate per 1000 episodes. RESULTS The majority of patients were treated with NS (n = 43,841 [88%]) compared with LR (n = 1762 [4%]) or both NS and LR (n = 4134 [8%]). Hospital-year-specific practice patterns were used to investigate the effect of fluid type across resuscitation fluid groups. Total adjusted cost was $1160 less (95% confidence interval, -1468 to -852), or -14.2%, for cases with any episode of LR compared with NS only. Length of stay was not different across groups. The rate of cerebral edema per 1000 episodes was 12.7 for cases with any episode of LR compared with 34.6 NS only (difference, -21.9; 95% confidence interval, -30.4 to -13.3). CONCLUSIONS Ringer's lactate was infrequently used for resuscitation of pediatric DKA patients. However, resuscitation with LR compared with NS was associated with lower total cost and rates of CE. Further investigation using patient-level clinical and laboratory data is needed to evaluate factors that drive cost and risk of CE development with each fluid.
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Affiliation(s)
- Kelly R Bergmann
- From the Department of Emergency Medicine, Children's Hospitals and Clinics of Minnesota, Minneapolis
| | - M Jennifer Abuzzahab
- Department of Pediatric Endocrinology and McNeely Diabetes Center, Children's Hospitals and Clinics of Minnesota, St Paul
| | | | - Joe Arms
- From the Department of Emergency Medicine, Children's Hospitals and Clinics of Minnesota, Minneapolis
| | - Gretchen Cutler
- From the Department of Emergency Medicine, Children's Hospitals and Clinics of Minnesota, Minneapolis
| | - Eric Christensen
- Research and Sponsored Programs, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN
| | - Mike Finch
- Research and Sponsored Programs, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN
| | - Anupam Kharbanda
- From the Department of Emergency Medicine, Children's Hospitals and Clinics of Minnesota, Minneapolis
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Badawi NES, Hafez M, Eldin HS, Abdelatif HM, Atef S, Ismail MM, Arafa N. Outcome of the use of 0.9% saline versus 0.45% saline for fluid rehydration in moderate and severe diabetic ketoacidosis in children. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2021. [DOI: 10.1186/s43054-021-00057-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
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.
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Long B, Lentz S, Koyfman A, Gottlieb M. Euglycemic diabetic ketoacidosis: Etiologies, evaluation, and management. Am J Emerg Med 2021; 44:157-160. [PMID: 33626481 DOI: 10.1016/j.ajem.2021.02.015] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/19/2021] [Accepted: 02/08/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Diabetic ketoacidosis is an endocrine emergency. A subset of diabetic patients may present with relative euglycemia with acidosis, known as euglycemic diabetic ketoacidosis (EDKA), which is often misdiagnosed due to a serum glucose <250 mg/dL. OBJECTIVE This narrative review evaluates the pathogenesis, diagnosis, and management of EDKA for emergency clinicians. DISCUSSION EDKA is comprised of serum glucose <250 mg/dL with an anion gap metabolic acidosis and ketosis. It most commonly occurs in patients with a history of low glucose states such as starvation, chronic liver disease, pregnancy, infection, and alcohol use. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which result in increased urinary glucose excretion, are also associated with EDKA. The underlying pathophysiology involves insulin deficiency or resistance with glucagon release, poor glucose availability, ketone body production, and urinary glucose excretion. Patients typically present with nausea, vomiting, malaise, or fatigue. The physician must determine and treat the underlying etiology of EDKA. Laboratory assessment includes venous blood gas for serum pH, bicarbonate, and ketones. Management includes resuscitation with intravenous fluids, insulin, and glucose, with treatment of the underlying etiology. CONCLUSIONS Clinician knowledge of this condition can improve the evaluation and management of patients with EDKA.
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Affiliation(s)
- Brit Long
- Department of Emergency Medicine, Brooke Army Medical Center, 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States of America.
| | - Skyler Lentz
- Division of Emergency Medicine, Department of Surgery, Larner College of Medicine, University of Vermont, Burlington, VT, United States of America
| | - Alex Koyfman
- The University of Texas Southwestern Medical Center, Department of Emergency Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States of America
| | - Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, IL 60612, United States of America
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Muneer M, Akbar I. Acute Metabolic Emergencies in Diabetes: DKA, HHS and EDKA. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1307:85-114. [PMID: 32488607 DOI: 10.1007/5584_2020_545] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Emergency admissions due to acute metabolic crisis in patients with diabetes remain some of the most common and challenging conditions. DKA (Diabetic Ketoacidosis), HHS (Hyperglycaemic Hyperosmolar State) and recently focused EDKA (Euglycaemic Diabetic Ketoacidosis) are life-threatening different entities. DKA and HHS have distinctly different pathophysiology but basic management protocols are the same. EDKA is just like DKA but without hyperglycaemia. T1D, particularly children are vulnerable to DKA and T2D, particularly elderly with comorbidities are vulnerable to HHS. But these are not always the rule, these acute conditions are often occur in different age groups with diabetes. It is essential to have a coordinated care from the multidisciplinary team to ensure the timely delivery of right treatment. DKA and HHS, in many instances can present as a mixed entity as well. Mortality rate is higher for HHS than DKA but incidences of DKA are much higher than HHS. The prevalence of HHS in children and young adults are increasing due to exponential growth of obesity and increasing T2D cases in this age group. Following introduction of SGLT2i (Sodium-GLucose co-Transporter-2 inhibitor) for T2D and off-label use in T1D, some incidences of EDKA has been reported. Healthcare professionals should be more vigilant during acute illness in diabetes patients on SGLT2i without hyperglycaemia to rule out EDKA. Middle aged, mildly obese and antibody negative patients who apparently resemble as T2D without any precipitating causes sometime end up with DKA which is classified as KPD (Ketosis-prone diabetes). Many cases can be prevented by following 'Sick day rules'. Better access to medical care, structured diabetes education to patients and caregivers are key measures to prevent acute metabolic crisis.
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Affiliation(s)
| | - Ijaz Akbar
- Shukat Khanam Cancer Hospital and Research Centre, Lahore, Pakistan
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30
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Sahu S, Sam A, Ponnappan K. Fluid management in kidney disease patients for nontransplant and transplantation surgeries. BALI JOURNAL OF ANESTHESIOLOGY 2021. [DOI: 10.4103/bjoa.bjoa_203_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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31
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Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, Coston TD, Felbinger M, Flemmons LN, Hellervik SM, Lindsell CJ, Liu D, McCoin NS, Niswender KD, Slovis CM, Stollings JL, Wang L, Rice TW, Semler MW. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open 2020; 3:e2024596. [PMID: 33196806 PMCID: PMC7670314 DOI: 10.1001/jamanetworkopen.2020.24596] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 09/08/2020] [Indexed: 12/14/2022] Open
Abstract
Importance Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline. Objective To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA. Design, Setting, and Participants This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020. Interventions Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule. Main Outcomes and Measures The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion. Results Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03). Conclusions and Relevance In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA. Trial Registration ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.
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Affiliation(s)
- Wesley H. Self
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Christopher S. Evans
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Cathy A. Jenkins
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ryan M. Brown
- Asheville Pulmonary and Critical Care Associates, Asheville, North Carolina
| | - Jonathan D. Casey
- Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Sean P. Collins
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Taylor D. Coston
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Matthew Felbinger
- Department of Pharmacy Services, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lisa N. Flemmons
- Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Susan M. Hellervik
- Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | | | - Dandan Liu
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Nicole S. McCoin
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Kevin D. Niswender
- Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee
- Veterans Affairs Tennessee Valley Healthcare System, Nashville
| | - Corey M. Slovis
- Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Joanna L. Stollings
- Department of Pharmacy Services, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Li Wang
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Todd W. Rice
- Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Matthew W. Semler
- Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
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Kilic O, Gultekin Y, Yazici S. The Impact of Intravenous Fluid Therapy on Acid-Base Status of Critically Ill Adults: A Stewart Approach-Based Perspective. Int J Nephrol Renovasc Dis 2020; 13:219-230. [PMID: 33061531 PMCID: PMC7534048 DOI: 10.2147/ijnrd.s266864] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/14/2020] [Indexed: 12/25/2022] Open
Abstract
One of the most important tasks of physicians working in intensive care units (ICUs) is to arrange intravenous fluid therapy. The primary indications of the need for intravenous fluid therapy in ICUs are in cases of resuscitation, maintenance, or replacement, but we also load intravenous fluid for purposes such as fluid creep (including drug dilution and keeping venous lines patent) as well as nutrition. However, in doing so, some facts are ignored or overlooked, resulting in an acid-base disturbance. Regardless of the type and content of the fluid entering the body through an intravenous route, it may impair the acid-base balance depending on the rate, volume, and duration of the administration. The mechanism involved in acid-base disturbances induced by intravenous fluid therapy is easier to understand with the help of the physical-chemical approach proposed by Canadian physiologist, Peter Stewart. It is possible to establish a quantitative link between fluid therapy and acid–base disturbance using the Stewart principles. However, it is not possible to accomplish this with the traditional approach; moreover, it may not be noticed sometimes due to the normalization of pH or standard base excess induced by compensatory mechanisms. The clinical significance of fluid-induced acid-base disturbances has not been completely clarified yet. Nevertheless, as fluid therapy may be the cause of unexplained acid-base disorders that may lead to confusion and elicit unnecessary investigation, more attention must be paid to understand this issue. Therefore, the aim of this paper is to address the effects of different types of fluid therapies on acid-base balance using the simplified perspective of Stewart principles. Overall, the paper intends to help recognize fluid-induced acid-base disturbance through bedside evaluation and choose an appropriate fluid by considering the acid-base status of a patient.
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Affiliation(s)
- Ozgur Kilic
- Siyami Ersek Thoracic and Cardiovascular Surgery Center, Cardiology Department, Cardiac Intensive Care Unit, Istanbul, Turkey
| | - Yucel Gultekin
- Mersin University Hospital, General Surgery Department, Mersin, Turkey
| | - Selcuk Yazici
- Siyami Ersek Thoracic and Cardiovascular Surgery Center, Cardiology Department, Cardiac Intensive Care Unit, Istanbul, Turkey
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Long B, Willis GC, Lentz S, Koyfman A, Gottlieb M. Evaluation and Management of the Critically Ill Adult With Diabetic Ketoacidosis. J Emerg Med 2020; 59:371-383. [DOI: 10.1016/j.jemermed.2020.06.059] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 05/24/2020] [Accepted: 06/11/2020] [Indexed: 12/19/2022]
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Hahn RG, Svensson R, Zdolsek JH. Kinetics of crystalloid fluid in hyperglycemia; an open-label exploratory clinical trial. Acta Anaesthesiol Scand 2020; 64:1177-1186. [PMID: 32386325 DOI: 10.1111/aas.13614] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/16/2020] [Accepted: 05/03/2020] [Indexed: 01/24/2023]
Abstract
BACKGROUND Infusion with 0.9% saline is a mainstay in the treatment of severe hyperglycemia, but the kinetics of the saline volume in this setting has not been studied. METHODS An intravenous infusion of 1 L of 0.9% saline over 30 minutes was given on 31 occasions to 17 patients with hyperglycemia due to poorly controlled diabetes (mean age 51 years). A two-volume kinetic model was fitted to serial data on the hemodilution and urinary excretion, using mixed-effects modeling software. RESULTS Plasma glucose was 36 ± 9 mmol/L on arrival to the hospital. The central volume of distribution (the plasma) was only 2.38 L (mean; 95% confidence interval 1.73-3.04) on the day of admission. Uptake into a remote compartment, believed to be the cells, amounted to 300 mL of the first liter of saline, although only small amounts of insulin were given. Plasma glucose, plasma bicarbonate, urine glucose, and plasma creatinine served as covariates in the kinetic model and mathematically affected the urinary excretion. For example, elimination of the infused fluid tripled from an increase in plasma glucose from 5 to 35 mmol/L and doubled from a reduction in plasma bicarbonate from 24 to 5 mmol/L. CONCLUSIONS The excretion of 0.9% saline was increased depending on the degree of hyperglycemia. The kinetics was characterized by glucose-accelerated diuresis, and an intracellular uptake that occurred at two thirds the urine flow rate. These data could help to determine appropriate volumes and rates of infusion of crystalloids in hyperglycemia.
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Affiliation(s)
- Robert G. Hahn
- Research Unit Södertälje HospitalKarolinska Institutet at Danderyds Hospital (KIDS) Södertälje Sweden
| | - Robert Svensson
- Department of Anesthesiology and Intensive Care Vrinnevi Hospital Norrköping Sweden
| | - Joachim H. Zdolsek
- Department of Anaesthesiology and Intensive Care Department of Medical and Health Sciences Linköping University Linköping Sweden
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Hammond S, Wignell A, Cooling P, Barrett DA, Davies P. Plasma-Lyte 148 and Plasma-Lyte 148 + 5% glucose compatibility with commonly used critical care drugs. Intensive Care Med Exp 2020; 8:25. [PMID: 32577941 PMCID: PMC7311557 DOI: 10.1186/s40635-020-00311-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 05/26/2020] [Indexed: 01/02/2023] Open
Abstract
PURPOSE Plasma-Lyte is a balanced, crystalloid intravenous fluid which has been shown to avoid the hyperchloremic metabolic acidosis associated with 0.9% sodium chloride. Data on physical, pH and chemical compatibility with other medicines are essential. METHODS The compatibility of adrenaline, dobutamine, dopamine, furosemide, midazolam, morphine and milrinone with Plasma-Lyte 148 (PLA) and Plasma-Lyte 148 with 5% glucose (PLA-G) was investigated. Control solutions were 0.9% sodium chloride and 5% glucose. Chemical stability was defined as < 5% concentration change with high-performance liquid chromatography (HPLC). Physical compatibility was assessed by checking for colour changes and precipitate formation. The pH of the admixtures was considered acceptable if between 5 and 9 at all time points. Six repeats were carried out for HPLC, 2 for physical compatibility checks and pH measurements, with all admixtures being tested at 0, 2 and 24 h after mixing. RESULTS All combinations were found to be chemically stable at 0, 2 and 24 h apart from furosemide with PLA-G at 24 h and midazolam with PLA or PLA-G at both 2 and 24 h. Only midazolam was physically incompatible when mixed with both Plasma-Lyte solutions. The pH remained stable in all admixtures, although not all pH values recorded were within the range of 5-9. CONCLUSION All drugs excluding furosemide and midazolam were shown to be chemically, physically and pH stable at the tested concentrations when diluted with PLA and PLA-G.
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Affiliation(s)
- Sophie Hammond
- School of Medicine, University of Nottingham, Nottingham, UK
- Paediatric Critical Care Unit, Nottingham Children's Hospital, Derby Road, Nottingham, UK
| | - Andrew Wignell
- Paediatric Critical Care Unit, Nottingham Children's Hospital, Derby Road, Nottingham, UK
- Pharmacy Department, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Paul Cooling
- Division of Advanced Materials and Healthcare Technologies, School of Pharmacy, University of Nottingham, Nottingham, UK
| | - David A Barrett
- Division of Advanced Materials and Healthcare Technologies, School of Pharmacy, University of Nottingham, Nottingham, UK
| | - Patrick Davies
- School of Medicine, University of Nottingham, Nottingham, UK.
- Paediatric Critical Care Unit, Nottingham Children's Hospital, Derby Road, Nottingham, UK.
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Haines RW, Kirwan CJ, Prowle JR. Managing Chloride and Bicarbonate in the Prevention and Treatment of Acute Kidney Injury. Semin Nephrol 2020; 39:473-483. [PMID: 31514911 DOI: 10.1016/j.semnephrol.2019.06.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Intravenous crystalloid therapy is one of the most ubiquitous aspects of hospital and critical care medicine. In recent years, there has been increasing focus on the electrolyte composition, and particularly chloride content, of crystalloid solutions. This has led to increasing clinical adoption of balanced solutions, containing substrates for bicarbonate generation and consequently a lower chloride content, in place of 0.9% saline. In this article we review the physiochemical rationale for avoidance of 0.9% saline and the effects of hyperchloremic acidosis on renal physiology. Finally, we review the current evidence and rationale for use of balanced solutions greater than 0.9% saline in acutely ill patients in a variety of clinical settings, as well as considering the role for sodium bicarbonate in preventing or correcting metabolic acidosis. In conclusion, there is a strong physiological rationale for avoidance of iatrogenic hyperchloremic acidosis from 0.9% saline administration in acutely unwell patients and an association with adverse renal outcomes in several studies. However, evidence from large definitive multicenter randomized trials is not yet available to establish the dose-relationship between 0.9% saline administration and potential harm and inform us if some 0.9% saline use is acceptable or if any exposure confers harm.
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Affiliation(s)
- Ryan W Haines
- Adult Critical Care Unit, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Christopher J Kirwan
- Adult Critical Care Unit, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; Department of Renal Medicine and Transplantation, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
| | - John R Prowle
- Adult Critical Care Unit, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom; William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; Department of Renal Medicine and Transplantation, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom.
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Williams V, Jayashree M, Nallasamy K, Dayal D, Rawat A. 0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2020; 24:1. [PMID: 31898531 PMCID: PMC6939333 DOI: 10.1186/s13054-019-2683-3] [Citation(s) in RCA: 276] [Impact Index Per Article: 55.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 11/22/2019] [Indexed: 01/21/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) is an important complication encountered during the course of diabetic ketoacidosis (DKA). Plasma-Lyte with lower chloride concentration than saline has been shown to be associated with reduced incidence of AKI in adults with septic shock. No study has compared this in DKA. METHODS This double-blind, parallel-arm, investigator-initiated, randomized controlled trial compared 0.9% saline with Plasma-Lyte-A as initial fluid in pediatric DKA. The study was done in a tertiary care, teaching, and referral hospital in India in children (> 1 month-12 years) with DKA as defined by ISPAD. Children with cerebral edema or known chronic kidney/liver disease or who had received pre-referral fluids and/or insulin were excluded. Sixty-six children were randomized to receive either Plasma-Lyte (n = 34) or 0.9% saline (n = 32). MAIN OUTCOMES Primary outcome was incidence of new or progressive AKI, defined as a composite outcome of change in creatinine (defined by KDIGO), estimated creatinine clearance (defined by p-RIFLE), and NGAL levels. The secondary outcomes were resolution of AKI, time to resolution of DKA (pH > 7.3, bicarbonate> 15 mEq/L & normal sensorium), change in chloride, pH and bicarbonate levels, proportion of in-hospital all-cause mortality, need for renal replacement therapy (RRT), and length of ICU and hospital stay. RESULTS Baseline characteristics were similar in both groups. The incidence of new or progressive AKI was similar in both [Plasma-Lyte 13 (38.2%) versus 0.9% saline 15 (46.9%); adjusted OR 1.22; 95% CI 0.43-3.43, p = 0.70]. The median (IQR) time to resolution of DKA in Plasma-Lyte-A and 0.9% saline were 14.5 (12 to 20) and 16 (8 to 20) h respectively. Time to resolution of AKI was similar in both [Plasma-Lyte 22.1 versus 0.9% saline 18.8 h (adjusted HR 1.72; 95% CI 0.83-3.57; p = 0.14)]. Length of hospital stay was also similar in both [Plasma-Lyte 9 (8 to 12) versus 0.9% saline 10 (8.25 to 11) days; p = 0.39]. CONCLUSIONS The incidence of new or progressive AKI and resolution of AKI were similar in both groups. Plasma-Lyte-A was similar to 0.9% Saline in time to resolution of DKA, need for RRT, mortality, and lengths of PICU and hospital stay. TRIAL REGISTRATION Clinical trial registry of India, CTRI/2018/05/014042 (ctri.nic.in) (Retrospectively registered).
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Affiliation(s)
- Vijai Williams
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Muralidharan Jayashree
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
| | - Karthi Nallasamy
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Devi Dayal
- Division of Pediatric Endocrinology, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Amit Rawat
- Division of Pediatric Allergy & Immunology, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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Rawat N, Sahni N, Yaddanapudi L. Comparison of Commercially Available Balanced Salt Solution and Ringer's Lactate on Extent of Correction of Metabolic Acidosis in Critically Ill Patients. Indian J Crit Care Med 2020; 24:539-543. [PMID: 32963436 PMCID: PMC7482348 DOI: 10.5005/jp-journals-10071-23488] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Introduction Appropriate early fluid resuscitation is ubiquitous for critically ill patients with metabolic acidosis. Owing to harmful effects of normal saline, commercially prepared balanced salt solutions are being used. However, there is no study comparing use of Ringer's lactate (RL) and commercially available balanced salt solutions in critically ill patients. Materials and methods A randomized controlled trial was conducted during July 2016 to December 2017. Fifty adult patients admitted to intensive care unit with metabolic acidosis were randomized into group RL or group acetate solution (AC). Respective trial fluid was administered at 20 mL/kg/hour for first hour and 10 mL/kg/hour for second hour. Arterial blood gas analysis samples were taken 15 minutes apart. The fluid resuscitation was continued till pH got corrected to 7.3 or 2 hours, whichever was earlier. The primary aim was to compare time to correct metabolic acidosis in both the groups. The secondary outcomes were the extent of correction of metabolic acidosis, total volume of fluid used, and total cost per patient. Results Demographic parameters, APACHE II score, and baseline investigations were comparable. The metabolic acidosis got corrected in 12 patients in group AC and 10 patients in group RL (p value = 0.66). The mean time for correction of metabolic acidosis was 57 ± 3.85 minutes in group RL and 56.25 ± 4.22 minutes in group AC (p value =0.95). The extent of correction of metabolic acidosis and total volume of fluid used was also comparable (p value = 0.05). However, the cost of fluid used was significantly higher in group AC (p value < 0.01). Conclusion During administration of balanced salt solutions, RL or AC, in critically ill patients with metabolic acidosis, AC did not confer any advantage in time to or extent of correction of metabolic acidosis. Clinical significance There is no difference in acid–base status with use of different types of balanced salt solutions for resuscitation in critically ill patients. How to cite this article Rawat N, Sahni N, Yaddanapudi L. Comparison of Commercially Available Balanced Salt Solution and Ringer's Lactate on Extent of Correction of Metabolic Acidosis in Critically Ill Patients. Indian J Crit Care Med 2020;24(7):539–543.
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Affiliation(s)
- Neha Rawat
- Department of Anesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Neeru Sahni
- Department of Anesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Lakshminarayana Yaddanapudi
- Department of Anesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Kang D, Yoo KY. Fluid management in perioperative and critically ill patients. Acute Crit Care 2019; 34:235-245. [PMID: 31795621 PMCID: PMC6895467 DOI: 10.4266/acc.2019.00717] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 11/05/2019] [Indexed: 12/29/2022] Open
Abstract
Fluid therapy to restore and/or maintain tissue perfusion may affect patient outcomes in perioperative, emergency, and intensive care. Kinetic analyses and outcome-oriented studies have provided more insight into fluid management. Crystalloids are slowly distributed to the interstitial space, and the efficiency (proportion of infused fluid retained in the bloodstream) is 50%−75% as long as infusion continues and may increase up to 100% when the arterial pressure has decreased. Elimination of the infused fluid during general anesthesia and surgery is very slow, amounting to only 10%–20% compared with that in conscious patients. When the endothelial glycocalyx layer is degraded in sepsis or trauma-induced systemic inflammation, turnover of colloids and crystalloids is accelerated and the efficiency is reduced, which may lead to tissue edema, inflammation, poor wound healing, and organ dysfunction. Balanced crystalloids are pragmatic initial resuscitation fluids and improve patient outcomes compared to saline (0.9% sodium chloride). Albumin may be beneficial, but other synthetic colloids appear to increase the risk of acute kidney injury and death among patients in the intensive care unit. Fluid kinetics is likely to change based on patient physiological conditions (e.g., general anesthesia, surgery, stress, dehydration, blood pressure, or inflammation) and fluid types. To maximize efficacy and minimize iatrogenic side effects, fluids should be prescribed based on individual patient factors, disease states, and other treatment remedies.
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Affiliation(s)
- Dongho Kang
- Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Kyung Yeon Yoo
- Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
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Hammond DA, Lam SW, Rech MA, Smith MN, Westrick J, Trivedi AP, Balk RA. Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis. Ann Pharmacother 2019; 54:5-13. [DOI: 10.1177/1060028019866420] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: The optimal resuscitative fluid remains controversial. Objective: To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2 = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2 = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2 = 42%). Conclusion and Relevance: Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.
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Goad NT, Bakhru RN, Pirkle JL, Kenes MT. Association of Hyperchloremia With Unfavorable Clinical Outcomes in Adults With Diabetic Ketoacidosis. J Intensive Care Med 2019; 35:1307-1313. [PMID: 31342846 DOI: 10.1177/0885066619865469] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVE Hyperchloremia is associated with worsened outcomes in various clinical situations; however, data are limited in patients with diabetic ketoacidosis (DKA). The purpose of this study was to determine the effect of hyperchloremia on time to DKA resolution. METHODS We conducted a retrospective cohort study of adult patients admitted with incident DKA from January 2013 through October 2017 and stratified by the development of hyperchloremia versus maintaining normochloremia. The primary outcome was time to final DKA resolution. Secondary outcomes included time to initial DKA resolution, incidence of acute kidney injury (AKI) on admission, in-hospital development of AKI, and hospital length of stay (LOS). RESULTS Of the 102 patients included, 52 developed hyperchloremia. Patients with hyperchloremia had longer times to final DKA resolution compared to those with normochloremia (median 22.3 [interquartile range, IQR, 15.2-36.9] vs 14.2 [IQR 8.8-21.1] hours; P = .001). Time to initial DKA resolution was also longer in patients who developed hyperchloremia compared to those who did not (median 16.3 vs 10.9 hours; P = .024). More patients with hyperchloremia developed in-hospital AKI (26.9% vs 8.0%; P = .01). Median hospital LOS was significantly longer in the hyperchloremia cohort (P < .001). On Cox regression analysis, time to DKA resolution was significantly longer with each 1 mmol/L increase in serum chloride (HR 0.951; P < .001). CONCLUSION The presence of hyperchloremia in patients with DKA was associated with increased time to DKA resolution, risk of in-hospital AKI, and hospital LOS. Further evaluation of the avoidance or treatment of hyperchloremia in DKA is needed.
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Affiliation(s)
- Nathan T Goad
- Department of Pharmacy, 12280Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Rita N Bakhru
- Department of Pulmonary, Critical Care, Allergy, and Immunologic Diseases, 12280Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - James L Pirkle
- Department of Nephrology, 12280Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Michael T Kenes
- Department of Pharmacy, 12280Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
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Usman A, Makmor Bakry M, Mustafa N, Rehman IU, Bukhsh A, Lee SWH, Khan TM. Correlation of acidosis-adjusted potassium level and cardiovascular outcomes in diabetic ketoacidosis: a systematic review. Diabetes Metab Syndr Obes 2019; 12:1323-1338. [PMID: 31496770 PMCID: PMC6689561 DOI: 10.2147/dmso.s208492] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 06/05/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND During the progress and resolution of a diabetic ketoacidosis (DKA) episode, potassium levels are significantly affected by the extent of acidosis. However, none of the current guidelines take into account acidosis during resuscitation of potassium level in DKA management, which may increase the risk of cardiovascular adverse events. OBJECTIVE To assess literature regarding the adjustment of potassium level using pH to calculate pH-adjusted corrected potassium level, and to observe the relationship of cardiovascular outcomes with reported potassium level and pH-adjusted corrected potassium in DKA. METHODOLOGY Seven databases were searched from inception to January 2018 for studies which had reported people with diabetes developing diabetic ketoacidosis, in relation to prevalence or incidence, fluid resuscitation or potassium supplementation treatment, treatment or cardiovascular outcomes, and experimentation with DKA management or insulin. Quality of studies was evaluated using Cochrane Risk of Bias and Newcastle Ottawa Scale. RESULTS Forty-seven studies were included in qualitative synthesis out of a total of 10,292 retrieved studies. Forty-one studies discussed the potassium level and blood pH at the time of admission, ten studies discussed cardiovascular outcomes, and only four studies concurrently discussed potassium level, pH, and cardiovascular outcomes. Only two studies were graded as good on the Newcastle Ottawa Scale. The reported potassium level was well within normal range (5.8 mmol/L), whereas pH rendered patients to be moderately acidotic (7.13). Surprisingly, none of the included studies mentioned pH-adjusted corrected potassium level and, hence, this was calculated later. Although mean corrected potassium was within the normal range (3.56 mmol/L), 13 studies had corrected potassium below 3.5 mmol/L and five had it below 3.0 mmol/L. Nevertheless, with the exception of one study, none discussed cardiovascular outcomes in the context of potassium or pH-adjusted potassium level. CONCLUSION The evidence surrounding cardiovascular outcomes during DKA episodes in light of a pH-adjusted corrected potassium level is scarce. A prospective observational, or preferably, an experimental study in this regard will ensure we can modify and enhance safety of existing DKA treatment protocols.
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Affiliation(s)
- Atif Usman
- School of Pharmacy, Monash University, Bandar Sunway, Selangor, Malaysia
- Correspondence: Atif UsmanSchool of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan47500, Bandar Sunway, Selangor, MalaysiaEmail
| | - Mohd Makmor Bakry
- Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Norlaila Mustafa
- Department of Endocrinology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Inayat Ur Rehman
- School of Pharmacy, Monash University, Bandar Sunway, Selangor, Malaysia
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Allah Bukhsh
- School of Pharmacy, Monash University, Bandar Sunway, Selangor, Malaysia
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Shaun Wen Huey Lee
- School of Pharmacy, Monash University, Bandar Sunway, Selangor, Malaysia
| | - Tahir Mehmood Khan
- School of Pharmacy, Monash University, Bandar Sunway, Selangor, Malaysia
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
- Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes, Health and Well-being Cluster, Global Asia in the 21st Century Platform, Monash University Malaysia, Selangor, Malaysia
- Tahir Mehmood KhanSchool of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan47500, Bandar Sunway, Selangor, MalaysiaEmail ;
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Jayashree M, Williams V, Iyer R. Fluid Therapy For Pediatric Patients With Diabetic Ketoacidosis: Current Perspectives. Diabetes Metab Syndr Obes 2019; 12:2355-2361. [PMID: 31814748 PMCID: PMC6858801 DOI: 10.2147/dmso.s194944] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Accepted: 10/24/2019] [Indexed: 12/19/2022] Open
Abstract
Diabetic ketoacidosis (DKA) is a preventable life-threatening complication of type 1 diabetes. Fluids form a crucial component of DKA therapy, goals being the restoration of intravascular, interstitial and intracellular compartments. Hydration reduces hyperglycemia by decreased counter-regulatory hormones, enhanced renal glucose clearance and augmented insulin sensitivity. However, for the last several decades, fluids in DKA have been subject of intense debate owing to their possible role in causation of cerebral edema (CE). Rehydration protocols have been modified to prevent major osmotic shifts, correct electrolyte imbalances and avoid cerebral or pulmonary edema. In DKA, a conservative deficit assumption ranging from 6.5% to 8.5% is preferred. Normal saline (0.9%) has been the traditional fluid of choice, for both, volume resuscitation and deficit replacement in DKA. However, the risk of AKI with its liberal chloride content remains a contentious issue. On the other hand, balanced crystalloids with restricted chloride content need more exploration in children with DKA, both with respect to DKA resolution and AKI. Although fluids are an integral part of DKA management, a fine balance is needed to avoid under-hydration or over-hydration during DKA management. In this narrative review, we discuss the current perspectives on fluids in pediatric DKA.
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Affiliation(s)
- Muralidharan Jayashree
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
- Correspondence: Muralidharan Jayashree Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, IndiaTel +91 172 275 5311Fax +91-172-2744401 Email
| | - Vijai Williams
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajalakshmi Iyer
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Rein JL, Coca SG. "I don't get no respect": the role of chloride in acute kidney injury. Am J Physiol Renal Physiol 2018; 316:F587-F605. [PMID: 30539650 DOI: 10.1152/ajprenal.00130.2018] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Acute kidney injury (AKI) is a major public health problem that complicates 10-40% of hospital admissions. Importantly, AKI is independently associated with increased risk of progression to chronic kidney disease, end-stage renal disease, cardiovascular events, and increased risk of in-hospital and long-term mortality. The chloride content of intravenous fluid has garnered much attention over the last decade, as well as its association with excess use and adverse outcomes, including AKI. Numerous studies show that changes in serum chloride concentration, independent of serum sodium and bicarbonate, are associated with increased risk of AKI, morbidity, and mortality. This comprehensive review details the complex renal physiology regarding the role of chloride in regulating renal blood flow, glomerular filtration rate, tubuloglomerular feedback, and tubular injury, as well as the findings of clinical research related to the chloride content of intravenous fluids, changes in serum chloride concentration, and AKI. Chloride is underappreciated in both physiology and pathophysiology. Although the exact mechanism is debated, avoidance of excessive chloride administration is a reasonable treatment option for all patients and especially in those at risk for AKI. Therefore, high-risk patients and those with "incipient" AKI should receive balanced solutions rather than normal saline to minimize the risk of AKI.
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Affiliation(s)
- Joshua L Rein
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York
| | - Steven G Coca
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York
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Ma P, Wang B, Zhang J, Shen X, Yu L, Dou X. Balanced crystalloids for intravenous fluid therapy in critically ill and non-critically ill patients: A protocol for systematic review and network meta-analyses. Medicine (Baltimore) 2018; 97:e13683. [PMID: 30572491 PMCID: PMC6320151 DOI: 10.1097/md.0000000000013683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Accepted: 11/22/2018] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND The balanced crystalloids have become a substitute for saline for fluid resuscitation. Some studies have investigated the clinical effect and adverse event of differently balanced crystalloids, but they have no consistent conclusions. This study aims to assess and compare the effect of differently balanced crystalloids for intravenous fluid therapy in critically ill and non-critically ill patients using network meta-analysis (NMA). METHODS Electronic databases including PubMed, EMBASE, Cochrane Library, Web of Science, Clinical Trials.gov, and the International Clinical Trials Registry Platform (ICTRP) will be searched from inception to April 2018. We will include randomized controlled trials (RCTs) that reported the effect and adverse event of balanced crystalloids. Risk of bias assessment of the included RCTs will be conducted according to the Cochrane Handbook 5.1.0. A Bayesian NMA will be performed using R software. GRADE will be used to explore the quality of evidence. RESULTS The results of this NMA will be published in a peer-reviewed journal. CONCLUSION This NMA will summarize the direct and indirect evidence to assess the effect of differently balanced crystalloids. ETHICS AND DISSEMINATION Ethics approval and patient consent are not required as this study is an NMA based on published studies. PROSPERO REGISTRATION NUMBER CRD42018093818.
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Affiliation(s)
- Peifen Ma
- Department of Nursing, Lanzhou University Second Hospital
- School of Nursing, Lanzhou University
| | - Bo Wang
- Department of Nursing, Rehabilitation Center Hospital of Gansu Province
| | - Jun Zhang
- School of Nursing, Gansu University of Chinese Medicine
| | - Xiping Shen
- Institute of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou, China
| | - Liping Yu
- Department of Nursing, Rehabilitation Center Hospital of Gansu Province
| | - Xinman Dou
- Department of Nursing, Lanzhou University Second Hospital
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Lee MH, Calder GL, Santamaria JD, MacIsaac RJ. Diabetic ketoacidosis in adult patients: an audit of factors influencing time to normalisation of metabolic parameters. Intern Med J 2018; 48:529-534. [PMID: 29316133 DOI: 10.1111/imj.13735] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 12/19/2017] [Accepted: 12/21/2017] [Indexed: 01/07/2023]
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is an acute life-threatening metabolic complication of diabetes that imposes substantial burden on our healthcare system. There is a paucity of published data in Australia assessing factors influencing time to resolution of DKA and length of stay (LOS). AIMS To identify factors that predict a slower time to resolution of DKA in adults with diabetes. METHODS Retrospective audit of patients admitted to St Vincent's Hospital Melbourne between 2010 to 2014 coded with a diagnosis of 'Diabetic Ketoacidosis'. The primary outcome was time to resolution of DKA based on normalisation of biochemical markers. Episodes of DKA within the wider Victorian hospital network were also explored. RESULTS Seventy-one patients met biochemical criteria for DKA; median age 31 years (26-45 years), 59% were male and 23% had newly diagnosed diabetes. Insulin omission was the most common precipitant (42%). Median time to resolution of DKA was 11 h (6.5-16.5 h). Individual factors associated with slower resolution of DKA were lower admission pH (P < 0.001) and higher admission serum potassium level (P = 0.03). Median LOS was 3 days (2-5 days), compared to a Victorian state-wide LOS of 2 days. Higher comorbidity scores were associated with longer LOS (P < 0.001). CONCLUSIONS Lower admission pH levels and higher admission serum potassium levels are independent predictors of slower time to resolution of DKA. This may assist to stratify patients with DKA using markers of severity to determine who may benefit from closer monitoring and to predict LOS.
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Affiliation(s)
- Melissa H Lee
- Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Genevieve L Calder
- Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - John D Santamaria
- Department of Intensive Care, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Richard J MacIsaac
- Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, Sperling MA, Codner E. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes 2018; 19 Suppl 27:155-177. [PMID: 29900641 DOI: 10.1111/pedi.12701] [Citation(s) in RCA: 396] [Impact Index Per Article: 56.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 05/31/2018] [Indexed: 12/22/2022] Open
Affiliation(s)
- Joseph I Wolfsdorf
- Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts
| | - Nicole Glaser
- Department of Pediatrics, Section of Endocrinology, University of California, Davis School of Medicine, Sacramento, California
| | - Michael Agus
- Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts.,Division of Critical Care Medicine, Boston Children's Hospital, Boston, Massachusetts
| | - Maria Fritsch
- Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
| | - Ragnar Hanas
- Department of Pediatrics, NU Hospital Group, Uddevalla and Sahlgrenska Academy, Gothenburg University, Uddevalla, Sweden
| | - Arleta Rewers
- Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado
| | - Mark A Sperling
- Division of Endocrinology, Diabetes and Metabolism, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ethel Codner
- Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile
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Laplante S, Makhija DU, Munson SH, Khangulov VS, Peyerl FW, Paluszkiewicz SM, Ravindranath AJ, Schermer CR. Impact of Fluid Choice in Systemic Inflammatory Response Syndrome Patients on Hospital Cost Savings. PHARMACOECONOMICS - OPEN 2018; 2:325-335. [PMID: 29623629 PMCID: PMC6103923 DOI: 10.1007/s41669-017-0055-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
BACKGROUND There is growing evidence of the benefits of intravenous fluid therapy with balanced crystalloids over 0.9% 'normal' saline. This analysis evaluated the economic impact of increasing usage of a calcium-free balanced crystalloid solution (BAL) in patients with systemic inflammatory response syndrome (SIRS) on an annual hospital budget. METHODS An Excel®-based economic model was developed to estimate costs associated with increased BAL usage (i.e., use in a greater proportion of patients), from the US hospital perspective, over a 5-year time horizon. Clinical inputs were based on the results of a retrospective Electronic Health Record (EHR) database analysis identifying significantly fewer complications among SIRS patients receiving predominantly BAL versus saline. Complication-associated costs, adjusted to 2015, were obtained from published reports. Scenario analyses examined cost impacts for hospitals of various sizes, with different BAL adoption levels and rates. RESULTS Base-case scenario analysis (300-bed hospital, 80% occupancy, current and year 5 BAL usage in 5 and 75% of SIRS patients, respectively, exponential year-over-year adoption) showed year 1 hospital savings of US$29,232 and cumulative 5-year savings of US$1.16M. Cumulative 5-year pharmacy savings were US$172,641. Scenario analyses demonstrated increasing cumulative 5-year savings with increasing hospital size, year 5 BAL usage in greater proportions of patients, and rapid/early BAL adoption. CONCLUSIONS Increased BAL usage represents an opportunity for hospitals and pharmacy departments to reduce complication-related costs associated with managing SIRS patients. The model suggests that savings could be expected across a range of scenarios, likely benefiting hospitals of various sizes and with different adoption capabilities.
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Affiliation(s)
| | - Dilip U. Makhija
- Baxter Healthcare Corporation, One Baxter Parkway, Deerfield, IL 60015 USA
| | - Sibyl H. Munson
- Boston Strategic Partners, Inc., 4 Wellington Street, Suite 3, Boston, MA 02118 USA
| | - Victor S. Khangulov
- Boston Strategic Partners, Inc., 4 Wellington Street, Suite 3, Boston, MA 02118 USA
| | - Fred W. Peyerl
- Boston Strategic Partners, Inc., 4 Wellington Street, Suite 3, Boston, MA 02118 USA
| | | | | | - Carol R. Schermer
- Department of Surgery, Advocate Medical Group, Downers Grove, IL 60515 USA
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Zayed YZM, Aburahma AMY, Barbarawi MO, Hamid K, Banifadel MRN, Rashdan L, Bachuwa GI. Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis. J Intensive Care 2018; 6:51. [PMID: 30140441 PMCID: PMC6098635 DOI: 10.1186/s40560-018-0320-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 08/07/2018] [Indexed: 02/03/2023] Open
Abstract
Objectives Intravenous fluids are one of the most used medical therapy for patients, especially critically ill patients. We conducted a meta-analysis comparing between balanced crystalloids and normal saline in critically ill patients and its effect on various clinical outcomes. Design Meta-analysis and systematic review of randomized clinical trials (RCTs). Methods and data source Electronic search was performed using PubMed, Cochrane library, and clinical trials.gov from inception through March 1, 2018, with inclusion of prospective studies that investigated one of the primary outcomes which were acute kidney injury (AKI) and in-hospital mortality while secondary outcomes were intensive care unit (ICU) mortality and new renal replacement therapy (RRT). Results Six RCTs were included. Total of 19,332 patients were included in the final analysis. There was no significant difference in in-hospital mortality (11.5% vs 12.2%; OR 0.92; 95% CI 0.85-1.01; P = 0.09; I2 = 0%), incidence of AKI (12% vs 12.7%, OR 0.92; 95% CI 0.84-1.01; P = 0.1; I2 = 0), overall ICU mortality (OR 0.9, 95% CI 0.81-1.01, P = 0.08, I2 = 0%), or need for new RRT (OR 0.92, 95% CI 0.67-1.28, P = 0.65, I2 = 38%) between balanced crystalloids and isotonic saline in critically ill patients. Conclusion Balanced crystalloids and isotonic saline have no difference on various clinical outcomes including in-hospital mortality, AKI, overall ICU mortality, and new RRT. Further powerful clinical trials are required to determine the relationship between crystalloid fluid type and clinical outcomes.
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Affiliation(s)
- Yazan Z M Zayed
- Internal Medicine Department, Hurley Medical Center/Michigan State University College of Human Medicine, Flint, MI USA.,East Lansing, USA
| | - Ahmed M Y Aburahma
- Internal Medicine Department, Hurley Medical Center/Michigan State University College of Human Medicine, Flint, MI USA
| | - Mahmoud O Barbarawi
- Internal Medicine Department, Hurley Medical Center/Michigan State University College of Human Medicine, Flint, MI USA
| | - Kewan Hamid
- Internal Medicine Department, Hurley Medical Center/Michigan State University College of Human Medicine, Flint, MI USA
| | - Momen R N Banifadel
- 2Internal Medicine Department, University of Toledo College of Medicine and Life Sciences, Toledo, OH USA
| | - Laith Rashdan
- Internal Medicine Department, Hurley Medical Center/Michigan State University College of Human Medicine, Flint, MI USA
| | - Ghassan I Bachuwa
- Internal Medicine Department, Hurley Medical Center/Michigan State University College of Human Medicine, Flint, MI USA
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Abstract
Crystalloid infusion is widely employed in patient care for volume replacement and resuscitation. In the United States the crystalloid of choice is often normal saline. Surgeons and anesthesiologists have long preferred buffered solutions such as Ringer's Lactate and Plasma-Lyte A. Normal saline is the solution most widely employed in medical and pediatric care, as well as in hematology and transfusion medicine. However, there is growing concern that normal saline is more toxic than balanced, buffered crystalloids such as Plasma-Lyte and Lactated Ringer's. Normal saline is the only solution recommended for red cell washing, administration and salvage in the USA, but Plasma-Lyte A is also FDA approved for these purposes. Lactated Ringer's has been traditionally avoided in these applications due to concerns over clotting, but existing research suggests this is not likely a problem. In animal models and clinical studies in various settings, normal saline can cause metabolic acidosis, vascular and renal function changes, as well as abdominal pain in comparison with balanced crystalloids. The one extant randomized trial suggests that in very small volumes (2 l or less) normal saline is not more toxic than other crystalloids. Recent evidence suggests that normal saline causes substantially more in vitro hemolysis than Plasma-Lyte A and similar solutions during short term storage (24 hours) after washing or intraoperative salvage. There are now abundant data to raise concerns as to whether normal saline is the safest replacement solution in infusion therapy, red cell washing and salvage, apheresis and similar uses. In the USA, Plasma-Lyte A is also FDA approved for use with blood components and is likely a safer solution for these purposes. Its only disadvantage is a higher cost. Additional studies of the safety of normal saline for virtually all current clinical uses are needed. It seems likely that normal saline will eventually be abandoned in favor of safer, more physiologic crystalloid solutions in the coming years.
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