Resolution Of Acidosis Research Articles

8243 Euglycemic Diabetic Ketoacidosis Unveiled: Delayed Presentation and Complications of SGLT-2 Inhibitor Therapy in a Multimorbid Patient - A Case Report

Abstract Disclosure: T. Amin: None. A.K. Bala: None. M.A. Jones: None. M.S. Akula: None. K. Chalasani: None. M. Patel: None. J. Cheng: None. Introduction: Normal serum glucose levels (<200 mg/dL) in euglycemic diabetic ketoacidosis (EDKA) can complicate the typical clinical presentation of diabetic ketoacidosis (DKA), posing a diagnostic challenge. SGLT-2 inhibitors, a class of antihyperglycemic drugs, have been rarely but significantly associated with EDKA. These inhibitors enhance renal glucose clearance by preventing glucose reabsorption via sodium-glucose cotransport. The increased renal clearance may contribute to the euglycemic picture, potentially leading to an underestimation of required insulin dosage, thereby precipitating ketoacidosis in EDKA. Although the mechanisms of EDKA are not fully understood, the association with SGLT-2 inhibitors is becoming increasingly evident. Case A 53-year-old male with a medical history of type 2 Diabetes Mellitus, coronary artery disease, chronic kidney disease, hyperlipidemia, was admitted to the trauma bay after a fall. Medications included empagliflozin, metformin, aspirin, amlodipine, spironolactone, and carvedilol. Upon presentation, he had a brief loss of consciousness, complained of headache and chest pain, and was found to have an epidural hematoma with regional brain compression on the CT head. Admission labs showed a blood glucose level of 172, an unremarkable anion gap, and normal renal and liver function tests. Due to traumatic brain injury, he was admitted to the ICU for neurological monitoring. Despite remaining neurologically stable, he developed hypoxia, necessitating intubation. After successful extubation, he exhibited worsening metabolic acidosis on the fourth day, with an elevated anion gap of 22 and a blood glucose level of 174. Arterial blood gas analysis revealed a pH of 7.3 (and elevated beta-hydroxybutyrate (>4), while lactic acid levels remained normal. Urine analysis showed elevated blood glucose (>1000) and ketones (>40). Home medications, metformin, and empagliflozin were appropriately withheld, but euglycemic DKA attributed to empagliflozin was diagnosed. Treatment included intravenous fluid resuscitation and insulin infusion, leading to resolution of acidosis and improved mentation within 24 hours. Conclusion: EDKA is a diagnosis of exclusion often overlooked in ICU patients due to diverse causes of high-anion gap metabolic acidosis. Typical cases occur while the patient is using the drug, often associated with triggers like illness, alcohol use, surgery, or starvation. SGLT2 inhibitors, such as empagliflozin, with a half-life of 12.4 hours, are expected to clear the bloodstream in about 48 hours, yet this case suggests an association with EDKA both during use and after drug cessation. This delayed presentation highlights additional risk considerations associated with SGLT2 inhibitors, guiding future clinical diagnoses of EDKA even several days post discontinuation. Presentation: 6/3/2024

Low dose insulin infusion versus the standard dose in children with diabetic ketoacidosis: a meta-analysis.

Aim: This systematic review aims to consolidate findings from current clinical trials that compare the effectiveness of insulin infusion at 0.05IU/kg/h versus 0.1IU/kg/h in managing pediatric diabetic ketoacidosis. Methods: We searched several databases, including PubMed, Embase, Scopus, Cochrane Central and Web of Science. Our primary outcomes were time to reach blood glucose ≤250mg/dl and time to resolution of acidosis. Secondary outcomes included rate of blood glucose decrease per hour, incidence of hypoglycemia, hypokalemia, treatment failure, and cerebral edema. Results & conclusion: The present study establishes that a low insulin dose exhibits comparable efficacy to the standard dosage for managing pediatric patients suffering from diabetic ketoacidosis, with a lower incidence of complications.

Evaluation of the Effect of Fluid and Electrolyte Therapy on Electrolytes and Acidosis Resolution Time in Diabetic Ketoacidosis

Objective: Fluid replacement and insulin infusion are the cornerstones of treatment of diabetic ketoacidosis, but the optimal volume, rate of infusion, and electrolyte content of fluid replacement have been controversial. The aim of this study was to investigate the effects of treatment on pH, bicarbonate (HCO3), anion gap, chloride, and potassium levels as well as time to resolution of acidosis in children with diabetic ketoacidosis. Material and Methods: Ninety-six episodes with diabetic ketoacidosis between January 2015-December 2017 were evaluated. Results: The mean resolution time of acidosis was 13.4±7.1 hours. Anion gap was returned to normal in 68 (70.8%) episodes at the 4th hour of treatment with a mean of 11±4.2 mmol/L. Episodes with potassium phosphate (KPO4) replacement resulted in a faster increase in pH and a significantly shorter resolution time of acidosis (p<0.001). Acidosis persisted at the 16th hour of treatment in episodes with lower pH, lower serum bicarbonate (HCO3) and higher white blood cell (WBC) counts on admission (p<0.001, p=0.003 p=0.033, respectively). Hyperchloremia (Cl/Na ratio > 0.79) was observed in 97% of cases after 8 hours of treatment. Conclusion: Although the value of the anion gap in predicting acidosis is controversial, severe DKA episodes and high white blood cell count at admission; potassium replacement with high amounts of chloride and KCl containing fluids given during treatment have been associated with a longer recovery time of acidosis.

The Two-Bag Method for Management of Adult Diabetic Ketoacidosis-Experience With 634 Patients.

To compare key resource utilization and safety outcomes of adult emergency department (ED) patients in diabetic ketoacidosis (DKA) managed via the Two-Bag or traditional One-Bag method. This is a retrospective review at an academic medical center ED. Patients were included if >18 years, met diagnostic criteria for DKA (pH ≤ 7.30, bicarbonate ≤ 18 mmol/L, anion gap ≥ 10), and were managed via a standardized order set (either Two-Bag or One-Bag Method). Comparisons used independent-groups t-tests for continuous variables and χ2 tests for binary variables. We identified 634 patients with DKA managed via the Two-Bag method, and 107 managed via the One-Bag method. Cohorts were similar in demographics and presenting laboratories. The Two-Bag Method was associated with 8.1 h shorter to first bicarbonate >18 mmol/L (11.9 vs 20.0, P < .001), and 24 fewer IV fluid bags (5.3 vs 29.7, P < .001). Incidence of hypokalemia (potassium <3.0 mmol/L) was 53% lower in the Two-Bag cohort (6.6 vs 14.0%, P = .03); incidence of hypoglycemia (glucose <70 mg/dL) was 5.8 versus 10.3%, P = .16. For adult ED patients in DKA, the Two-Bag Method was associated with faster resolution of acidosis, fewer IV fluid bags charged, lower incidence of hypokalemia, and trend toward lower incidence of hypoglycemia compared to the One-Bag Method.

Insulin Infusion Dosing in Pediatric Diabetic Ketoacidosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

We searched MEDLINE, EMBASE, PubMed, and Cochrane from inception to April 1, 2022. We included randomized controlled trials (RCTs) of children with DKA comparing intravenous insulin infusion administered at 0.05 units/kg/hr (low dose) versus 0.1 units/kg/hr (standard dose). We extracted data independently and in duplicate and pooled using a random effects model. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. We included four RCTs (n = 190 participants). In children with DKA, low-dose compared with standard-dose insulin infusion probably has no effect on time to resolution of hyperglycemia (mean difference [MD], 0.22 hr fewer; 95% CI, 1.19 hr fewer to 0.75 hr more; moderate certainty), or time to resolution of acidosis (MD, 0.61 hr more; 95% CI, 1.81 hr fewer to 3.02 hr more; moderate certainty). Low-dose insulin infusion probably decreases the incidence of hypokalemia (relative risk [RR], 0.65; 95% CI, 0.47-0.89; moderate certainty) and hypoglycemia (RR, 0.37; 95% CI, 0.15-0.80; moderate certainty), but may have no effect on rate of change of blood glucose (MD, 0.42 mmol/L/hr slower; 95% CI, 1 mmol/L/hr slower to 0.18 mmol/L/hr faster; low certainty). In children with DKA, the use of low-dose insulin infusion is probably as efficacious as standard-dose insulin, and probably reduces treatment-related adverse events. Imprecision limited the certainty in the outcomes of interest, and the generalizability of the results is limited by all studies being performed in a single country.

ODP225 Mixed Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome with recent diagnosis of Diabetes Mellitus.

Abstract Background Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia syndrome (HHS) are often discussed as two distinct clinical entities but can present in the same patient. Combined DKA and HHS is associated with higher mortality than either DKA or HHS alone. Clinical case: A 68 years old female diagnosed with type 2 diabetes 3 months prior to hospitalization was brought into the hospital with severe hyperglycemia and altered mental status. On exam she was unresponsive with grimace only to sternal rub. Pulse was elevated at 113, RR 31, temperature 100.3, and blood pressure 130/80. Initial labs showed severe hyperglycemia with glucose of 1454 (74-106 mg/dL), elevated beta-hydroxybutyrate of 8.6 (0. 02-0.27 mmol/L), sodium 138 (135-145 mmol/L), potassium 5.3 (3.6-5.2 mmol/L), serum bicarbonate 16 (21-32 mmol/L), anion gap 31 (6-18), plasma osmolality 353 (273-304 osm/kg), pH 7.33 (7.35-7.45) and lactic acid 4 (0.7-1.9 mmol/L). DKA protocol with normal saline, intravenous insulin infusion, and potassium replacement initiated and patient was transferred to ICU for further management. Sequential labs revealed development of hypernatremia with calculated free water deficit of 8.8 liters. Fluids changed to ½ normal saline. On Day 2 of hospitalization, she became responsive. She had resolution of acidosis but continued to have severe hypernatremia with peak sodium level of 163 on day 3. Urine studies showed urine osmolality of 700 mOsm/kg ruling out diabetes insipidus; urine sodium level was 5 mmol/L. Fluids were again changed to ¼ Normal saline with careful monitoring of serum sodium and glucose at 2 hour intervals. Hypernatremia resolved with aggressive fluid resuscitation. Her A1c prior to discharge was found to have increased to 13.3% from 6.5% (&amp;lt; 5.6%), 3 months prior. Prior to discharge she had measurable C-peptide, insulin autoantibodies and negative GAD antibodies making autoimmune diabetes unlikely. Conclusion Individuals with concomitant DKA and HHS may have normal sodium or even hyponatremia at presentation due to the pseudo-hyponatremia induced by severe hyperglycemia. However, actual sodium concentration may be markedly elevated due to the osmotic diuresis induced by severe hyperglycemia. Aggressive fluid resuscitation is required to treat the profound dehydration found in HHS but the serum sodium concentration must be monitored carefully. A switch from normal saline to hypotonic fluids may be necessary to treat hypernatremia in HHS but overly rapid correction of serum sodium must be avoided for volume overload especially in elderly, owing to heart failure and due to higher mortality. The incidence of hypernatremia is noted in 14% of children and 27% of adults, however degree of hypernatremia is variable from mild to moderate and in rare instances is severe. Presentation: No date and time listed

ODP192 Empagliflozin associated Euglycemic Diabetic Ketoacidosis and the Terrible Triad

Abstract Background Among diabetic patients, newer drug classes such as SGLT2i have been reported to present with Euglycemic Diabetic Ketoacidosis (eDKA), wherein these patients are without signs of elevated glucose levels. However, this condition can coexist with acute pancreatitis (AP) and hypertriglyceridemia (HTG), which is also known as the terrible triad. Clinical Case We were presented with a 31-year old diabetic male maintained on empagliflozin 25mg OD and metformin 500mg OD, discontinued his medication four months ago, and recently started retaking empagliflozin one week ago. He presented with drowsiness, severe abdominal pain rated as 9/10, and vomiting. An NGT was inserted and on further workup, acidosis was present on ABG with an anion gap of 28 mEq/L. AP was noted on abdominal ultrasound with an amylase of 768 U/L. CBG was 167mg/dL, Hba1c of 7.4%, Creatinine of 1. 05mg/dL, with ketonuria on urinalysis. Hydration was started with referral to endocrinology service. Insulin drip was started, and CBGs ranged from 145-229mg/dL while on drip. Hydration was increased accordingly, considering the patient's intake and output. Further workup was done, and lipid profile revealed severe hypertriglyceridemia at 1724.78mg/dL and elevated VLDL at 342mg/dL. Statin was prescribed, and eventually, insulin drip was titrated down with resolution of acidosis. Insulin was then shifted to subcutaneous regimen. Diet was also transitioned to clear liquids and eventually into diabetic diet. The patient was sent home and was uneventful after. eDKA develops due to increased glucagon secretion and decreased insulin production, promoting glucose to fat metabolism and ultimately stimulating ketogenesis. These agents decrease the blood glucose level by increasing urinary glucose excretion leading to a reduction in insulin secretion from the pancreatic β-cells. The terrible or enigmatic triad consisting of AP, HTG, and DKA/eDKA has been well reported but has a complex process. HTG results as a product of the reduced lipoprotein lipase activity in peripheral tissues, which decreases the removal of VLDL from the plasma. In AP cases, HTG only accounts for a minority (2-7%) of cases, but the risk was increased with levels above 1000mg/dL, such as in our patient. In the study by Simons-Linares et al., having the said triad had higher odds of having SIRS, shock, sepsis, and parenteral nutrition when compared to AP patients alone. eDKA patients can present with non-specific signs and symptoms such as nausea, vomiting, and abdominal pain, which can delay the diagnosis in patients. Fortunately, it was recognized early on, and there was a quick response in managing the case. Conclusion To date, there is scarcity among reports of the terrible triad, especially with empagliflozin use. Therefore, we can stress the importance of keen assessments and history taking in detecting the triad for an early aggressive approach to prevent adverse outcomes. Presentation: No date and time listed

A Rare Presentation of New-Onset Type 1 Diabetes Mellitus in a Developmentally Delayed Child With an Overlap of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are serious complications associated with diabetes mellitus (DM). HHS is a common diagnosis in adults but rare in children. DKA is a usual presentation for new-onset type 1 DM, although HHS is rarely a manifestation of new-onset type 1 DM. Diagnosis and management of HHS are challenging in pediatric patients, especially if they present with a mixed picture of HHS and DKA. We report an adolescent female with a new onset of type 1 DM presented as mixed DKA and HHS. Treatment included meticulous management of fluids and continuous insulin drip with the resolution of acidosis within 24 hours and hyperosmolar state at 96 hours of admission. Early differentiation of these two entities and meticulous fluid management improves the outcome and decreases the risk of complications such as cerebral edema, renal failure, and thrombosis, among others.

Normal Saline Versus Low Chloride Solutions in Treatment of Diabetic Ketoacidosis: A Systematic Review of Clinical Trials.

Traditionally, normal saline solution (NSS) has been the fluid of choice in diabetic ketoacidosis (DKA) patients, but the NSS is an acidic fluid and may lead to the delayed resolution of DKA. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry to compare the efficacy of low chloride solutions with normal saline solution in DKA resolution. Randomized clinical trials with normal saline as a control arm and low chloride solutions as an intervention arm were included. Four studies were included in the analysis. The investigated outcomes, including time to resolution for DKA and duration of insulin infusion, varied depending on the endpoint were reported in the studies. Overall, balanced solutions were generally associated with faster correction of pH. The time to reach overall DKA endpoints was comparable in both groups. We concluded that crystalloid solutions may be used as an initial resuscitation fluid in the DKA population and may lead to earlier resolution of acidosis. More clinical trial data is required to reach statistical significance for the hypothesis.

Efficacy and Safety of Low Dose Insulin Infusion against Standard Dose Insulin Infusion in Children with Diabetic Ketoacidosis- An Open Labelled Randomized Controlled Trial.

Objective:To compare the efficacy and safety of low dose insulin infusion (0.05 U/kg/h) against the standard dose insulin infusion (0.1 U/kg/h) in children with diabetic ketoacidosis.Method:Children (age <12 years, n = 30) presenting with diabetic ketoacidosis were enrolled and randomised to receive insulin infusion either as 0.05 U/kg/h (low dose) or 0.1 U/kg/h (standard dose) as an open labelled randomised controlled trial. The rest of the management was identical in both groups. The time taken for resolution of acidosis (pH ≥7.3 and HCO3 ≥15) was the primary outcome variable. The secondary outcome variables included the time taken until a decline in blood glucose to 250 mg/dl, the proportion of children developing hypoglycemia and hypokalemia, and any treatment failure.Results:The two groups were similar with respect to mean age, weight and gender distribution. New-onset diabetes was diagnosed on 24/30. The mean ± SD time for resolution of acidosis was similar between the groups; 27.0 ± 6.1 hours in the low dose group vs 23.4 ± 7.3 hours in standard dose group, P = 0.16. The mean time for the decline in blood glucose to 250 mg/dl was 13.0 ± 5.9 hours in low dose vs 11.6 ± 6.0 hours in standard dose group, P = 0.52. A lesser proportion of participants developed hypoglycemia and hypokalemia in the low dose group, though not statistically significant. There was no incidence of treatment failure in either group.Conclusion:Low dose insulin infusion is equally effective and safe as standard dose insulin infusion in children with diabetic ketoacidosis.

Diabetes ketoacidosis recovery in youth with newly diagnosed and established type 1 diabetes.

The objective of this study was to describe the differences in metabolic parameters and in time to recovery from diabetes ketoacidosis (DKA), between children and adolescents with newly diagnosed diabetes compared with established type 1 diabetes (T1DM). This was a single-center, retrospective study. The cohort consists of 356 children and adolescents with T1DM who had DKA during 2008-2018. Data were obtained from the patients' medical files. Recovery of DKA was defined as the resolution of acidosis (pH >7.3 and bicarbonate >15 meq/L). The mean time to recovery from DKA was significantly longer in patients with newly diagnosed diabetes than in those with established diabetes (13± versus 8.5± h) (p < 0.001). This difference was maintained in an analysis according to DKA severity: mild, moderate, and severe. pH at presentation did not differ between the groups, but bicarbonate at presentation was significantly lower in patients with newly diagnosed diabetes than in those with established diabetes, 9.9± versus 12± mmol/L (p < 0.001). Potassium and phosphorus levels were lower, and sodium and chloride levels were higher in patients with newly diagnosed diabetes than in those with established diabetes (p < 0.001). DKA is associated with a shorter recovery time in patients with established diabetes compared to newly diagnosed diabetes. This may have implications on the treatment of people with established diabetes. DKA is associated with a shorter recovery time in patients with established diabetes compared with newly diagnosed diabetes. Shorter recovery time in a patient with established diabetes compared with newly diagnosed diabetes was observed in any DKA severity. The time to recovery from DKA did not differ significantly between patients treated with an insulin pump and those treated with multiple daily injections. Triggers for DKA among patients with established diabetes were poor compliance with treatment, infection, pump dysfunction, and dehydration.

Stewart (physicochemical) approach versus conventional anion gap approach for resolution of metabolic acidosis in diabetic ketoacidosis

Diabetic ketoacidosis (DKA) frequently requires emergency admission. The anion gap approach is conventionally used for the diagnosis and documenting the resolution of acidosis during treatment. However, it fails to detect hyperchloremic acidosis during the resolution and may result in the prolongation of treatment. To determine the role of the Stewart approach of acid-base disorder during DKA management for the prediction of an earlier resolution. A prospective comparative study was conducted between January 2017 and December 2017 at a single academic hospital in north India. Patients aged above 12 years with a diagnosis of DKA were randomly divided into two groups—the conventional group and the Stewart group, according to the approach used for DKA resolution. The primary outcome was the time duration required for resolution. The secondary outcomes were the therapeutic requirement of intravenous fluid, insulin, and potassium, Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the time of resolution, and hospital stay. Forty-four DKA patients were equally distributed in the two groups with comparable baseline parameters. The Stewart group had early resolution of DKA (mean, 32.4±17.5 h versus 41.7±19.6 h; p value <0.001) at similar APACHE II scores. The duration of hospital stay was reduced but was not statistically significant (mean, 5.6±3.2 days versus 7.0±3.8 days; p value 0.16). The therapeutic requirement of fluid, insulin, and potassium was similar in groups. The Stewart approach may be a better alternative to the conventional anion gap approach for guiding the resolution of DKA.

P0144 / #1852: ROLE OF CAPILLARY BLOOD KETONE ASSAY IN DIAGNOSIS AND MANAGEMENT OF DKA IN PICU

Aims & Objectives: Diabetic Ketoacidosis (DKA) is a life-threatening, metabolic emergency in children. The capillary Beta Hydroxybutyrate (BHOB) is increasingly used in the diagnosis and management of DKA. The Objective of this study is to assess the clinical and statistical correlation of BHOB with standard acid variables such as pH and HCO3. Methods: We retrospectively reviewed electronic medical record of children (aged 2 mo-16yrs) with DKA from January 2018 to January 2020 admitted in PICU of The Indus Hospital. All children received the treatment according to standard protocol. Capillary blood BHOB were measured on admission and q 4-6 hourly along with blood glucose. All parameters were recorded on a structured sheet. Results: Among 1080 admissions, 26 patients (2.4%) were diagnosis as DKA. The mean age was 9.8±3.8 year and female were 54%. Half patients were newly diagnosed with 1DDM. Mild, moderate and severe cases of DKA were 19%, 50% and 31% respectively. The median time to resolution of acidosis was 17 (10-39) hour. At the time of resolution of acidosis, the correlation between capillary BHOB and blood pH (r=0.11, p=0.56), HCO3(r=0.37, p=0.04), AG (r=0.37, p=0.06), and BD (r=0.04,p=0.82) was noted. Hyperchloremia was present in 61.5%. Five patients (19.2%) developed AKI that recovered. There was a strong clinical correlation of BHOB with standard acid variables of DKA management. Conclusions: Bedside capillary blood BHOB is a simple, inexpensive, point-of-care test helps in diagnosis and treatment of DKA. It has a high potential of implication in clinical practice especially in resource limited settings.

Spontaneous pneumomediastinum and pneumopericardium in a child with severe diabetic ketoacidosis: A case report

Apart from being the most common endocrine emergency in the pediatric intensive care unit, some clinical manifestations of diabetic ketoacidosis such as vomiting and continued acidotic breathing may, on the rare occasion, lead to unexpected complications such as pneumomediastinum, pneumopericardium, pneumothorax, and subcutaneous emphysema. The differentials for the same include Hamman's syndrome secondary to forceful coughing or Valsalva maneuver, Boerhaave syndrome resulting from forceful vomiting, and even spontaneous air leaks due to severe swings in intrathoracic pressure during Kussmaul breathing, leading to alveolar rupture causing air leak. These complications may have subtle signs as well as a significant overlap in presentation and require a high index of suspicion to diagnose and careful evaluation to differentiate. We hereby report a 3-year-old child with new-onset type 1 diabetes mellitus in severe DKA, leading to pneumomediastinum and pneumopericardium where computed tomography of the thorax helped rule out differentials and the air leak resolved spontaneously with the resolution of acidosis.

Analysis of Prolonged Pediatric Intensive Care Stay in Children with Diabetic Ketoacidosis

Background: Diabetic ketoacidosis is one of most serious complication of diabetes requiring intensive care management. We aim to analyze various factors responsible for prolonged duration of stay in pediatric intensive care unit in a child with Diabetic Ketoacidosis.&#x0D; Materials and Methods: This was a hospital based prospective observational study conducted in Nobel Medical College and Teaching Hospital among children with Diabetic ketoacidosis over the period of one year. A total of 22 cases with Diabetic ketoacidosis aged 1 month to 18 years were included and clinical profile, laboratory reports including blood gas analysis were documented.&#x0D; Results: Among cases of Diabetic ketoacidosis, 4 (18%) cases were of mild Diabetic ketoacidosis, 4 cases (18%) were of moderate Diabetic ketoacidosis and 14 cases (64%) were of severe Diabetic ketoacidosis. Mean duration of Intensive care stay in new cases of Diabetic ketoacidosis was 69.46 hours which was significantly higher compared to old cases (30.66 hours) suggested by p value &lt; 0.0001. In 15 cases (68%), acidosis resolved in less than 48-55 hours, whereas 7 cases (32%) required more than 48-55 hours for resolution of acidosis, hence required longer Intensive care stay. Cases who required prolonged Pediatric Intensive care stay, sepsis was contributing factor in 3 cases (42.85%), one case (14.28%) has associated muscular dystrophy and 3 cases (42.85%) had hyperchloremia at the end of 48 hours.&#x0D; Conclusion: Presence of sepsis and Hyperchloremia are important reasons for prolonged stay in Intensive Care Unit in Diabetic ketoacidosis patients. Other associated chronic illness can also prolong intensive care stay in Diabetic ketoacidosis patients.

Initiative to Reduce Hospitalization for Pediatric Diabetic Ketoacidosis

Children with diabetic ketoacidosis (DKA) typically exhibit resolution of acidosis within hours of treatment, yet most are hospitalized. Aiming to

Role of capillary blood ketone assay in diagnosis and management of diabetic ketoacidosis in pediatric intensive care unit

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

SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event

Introduction: Programmed cell death protein 1 (PD-1) inhibitors stimulate the immune system to produce anti-tumor effects and are among a novel drug class of cancer immunotherapy. PD-1 inhibitors are associated with various immune related adverse events (IRAEs) owing to their indiscriminate activation of the immune system. IRAEs involving the endocrine system, particularly affecting the thyroid, pituitary and adrenal glands, are well-established. We however present a case of diabetic ketoacidosis (DKA), an exceedingly rare and life threatening immune-related endocrinopathy, precipitated by the PD-1 inhibitor Pembrolizumab. Clinical case: A 52-year-old female with PMH of T2DM (A1c 8.1%) and metastatic NSCLC (Non-Small Cell Lung Cancer) presented with 1-day history of nausea, vomiting, polyuria, and lethargy. She received an infusion of Pembrolizuab 5 days prior to onset of symptoms. On admission, she was found to have a BG of 617 mg/dL (reference range (RR): 65-99 mg/dL), ketonuria (3+; 80mg/dL; RR: negative), anion gap of 22 mEq/L (RR: 7-15 mEq/L), serum CO2 17 mEq/L (RR: 24-31 mEq/L), and arterial pH 7.29 (RR: 7.35-7.45). Infection work up was negative. She was treated for DKA with IV fluids and IV insulin. After resolution of acidosis, evaluation revealed normal adrenal and thyroid function but undetectable C-Peptide (< 0.9ng/mL; RR: 1.1-4.4 ng/mL) which was previously normal. Diabetes related antibodies were negative. The patient subsequently required insulin to maintain euglycemia, though she was previously treated with oral agents alone, and was discharged on basal bolus insulin. This series of events signifies the abrupt loss β cell function that resulted in profound insulinopenia and DKA. This is recognized to be a rare immune-related endocrinopathy secondary to Pembrolizumab, with DKA occurring in only 0.1% of patients in clinical trials. Pembrolizumab blocks PD-1 receptors on the surface of T cells in order to restore T cell anti-tumor function. This blockade can trigger T cell mediated destruction of various host cells. Pancreatic β cells express PD Ligand-1, which binds to PD-1 receptors as a mode to evade T cell immunity. PD-1 inhibition potentiates inflammation and destruction of pancreatic β cells resulting in worsening control of DM or in rare instances, fulminant β cell failure and DKA. There does not appear to be a dose dependent relationship or serum antibody markers predictive of this adverse event. Conclusion: The expanding use PD-1 inhibitors in cancer treatment has resulted in a host of IRAEs. This case highlights that clinicians and patients alike must be aware of the importance of recognizing DKA as a rare yet potentially lethal adverse event of PD-1 inhibitors. There is currently no clear method to predict which patients are at risk of developing DKA but early and regular screening for glucose intolerance should be standard of care when initiating anti-PD1 therapy.

Risk factors associated with resolution of diabetic ketoacidosis in pediatric critical care units

Objective: Diabetic ketoacidosis (DKA) is the main cause of morbidity and mortality in children with type-I Diabetes Mellitus. The goals of therapy are to correct dehydration, resolution of acidosis and fading of ketosis. Such serious complications necessitate closed monitoring of DKA patients with delicate, balanced therapy, probably at an intensive care facility. Regarding the fact that, each facility shoul determine the clinical profile of their own patient population, we aimed to investigate the risk factors for consequences and determine the timing of DKA resolution by analyzing the demographic and epidemiologic data, clinical outcome and the prognosis of diabetic ketoacidotic children admitted to PICU. Method: This descriptive, retrospective study was conducted in 105 children admitted to PICU with the complaints of DKA between January 2014 and December 2108. Demograhic data including age, gender, weight, height, body mass index (BMI), initial compliants with clinical findings and level of consciousness were recorded. Children were categorized into two groups depending on the timing of DM diagnosis (new onset of diabetes and established diabetes mellitus). DKA severity was determined by the degree of metabolic acidosis (mild, moderate, severe). SPSS-23 was used for statictics. Descriptive analyses were expressed as percentages, mean±standart deviation (SD), median with minimum and maximum values. Chi square and Fischer exact test were used for comparison of categorical variables. Student’s t-test, Mann Whitney U test and Wilcoxon rank sum test were assessed for continous variables. Pearson correlation coefficient and logistic regressions were used for correlations and to determine the risk factors. P-value < 0.05 was considered significant. Results: The patient demographics presented the mean age as 11.31±4.18 years, female/male ratio 1/1.4 and body mass index 18.48±4.48. Children were classified as mild DKA (29.5%), moderate DKA (35.2%) and severe DKA (35.2%) based on the acidosis severity. 48.6% of the patients had Kusmaull respiration; 30.5% had manifested altered consciousness. One patient had tomography-proven brain edema and had required mechanical ventilation due to neurological incapability to sustain airway Children with new onset of diabetes accounted for 51.4% of the study population. The mean age was 9.70±4.47 years; this group constituted a younger population compared the established DM patients (p<0.001). Altered mental state and kusmaull respiration also occurred at a higher rate and the major complaint seemed ae weight loss within two weeks (p=0.006, p=0.002, p<0.001 respectively). Children with established diabetes mellitus presented significant biochemical abnormalities in terms of elevated BUN and serum potassium levels (p<0.001, p<0.001); infections occurred as the major triggering factor for DKA at a rate of 80.4% at this group. We observed a positive correlation with DKA resolution with serum creatinine, calculated osmolality, anion gap (r=0.242, r=0.215, r=0.302) and a negative correlation with blood gas pH and HCO3 (r= -0.704, r= -0.694). In the multivariable regression model including age, gender, body mass index, PRISM-3 score, BUN, serum potassium, phosphate and chloride, only blood gas pH and new onset of diabetes appeared to be the independent risk factors for DKA resolution. 0.1 unit decrement in blood gas pH elongated the resolution by 3.76 hours (p<0.001, adjusted ratio: 0.743). New onset of diabetes mellitus also increased the length of resolution by 5.30 hours (p<0.001). Conclusions: Inıtial blood gas pH and presence of new onset of diabetes are the major risk factors in resolution of ketoacidosis.

Serum sodium and potassium levels as prognostic indicators in pediatric diabetic ketoacidosis

Introduction : Diabetic ketoacidosis (DKA),a common emergency encountered in children is characterized by deranged acid-base status and a myriad of electrolyte disturbances. Objective : This study was done with the objective of determining the effect of serum sodium and potassium levels on prognosis of children with DKA. Methods : This cross-sectional study was done in the pediatric intensive care unit of a tertiary care center, from January 2015 to September 2015. Children diagnosed with DKA were included in the study. Convenient sample size was adopted. In a structured proforma, demographic and medical history was noted. Serum sodium and potassium were determined by Ion Selective Electrode method at the time of diagnosis and 12 hourly, till resolution of acidosis. The clinical outcome of the child, the duration of insulin infusion and hospital stay were noted. Association between dependent and independent variables was determined by chi-square test and level of significance was fixed at 5%. Results : Thity three patients were included. The mortality rate was 13%. Twenty (60%) patients required insulin infusion for less than 24 hours and 18 (62%) stayed in hospital for less than 2 weeks. Hyperkalemia at presentation was significantly associated with mortality, hyponatremia at the time of admission was found to be significantly associated with prolonged hospital stay and abnormal sodium and potassium levels persisting at the end of 24 hours was significantly associated with need for prolonged insulin infusion. Conclusion : Presence of hyperkalemia and hyponatremia at admission and persistence of abnormal serum sodium and potassium levels beyond 24 hours are poor prognostic markers in children with DKA.