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Severe acidosis caused by starvation and stress

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Abstract

A 1-year-old boy had severe anoxic brain injury owing to a cardiorespiratory arrest. He had an initial metabolic acidosis, but this largely resolved by hospital day 2. He then had a persistent, profound metabolic acidosis. Evaluation on hospital day 6 found that the patient had ketonemia, ketonuria, and a normal serum glucose level; he had received no intravenous dextrose during his hospitalization. The dextrose-free fluids were given initially to protect his brain from the deleterious effects of hyperglycemia after brain injury. Continuation beyond 24 hours was inadvertent. The initiation of dextrose-containing intravenous fluids produced a rapid resolution of his metabolic acidosis. Starvation usually produces a mild metabolic acidosis, but when combined with physiologic stress, starvation may cause a severe metabolic acidosis. Among the few reports of severe starvation ketoacidosis, our case is unique because the patient was monitored closely in an intensive care unit, allowing us to describe the time course of the acidosis in detail.

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... 5,12 Ketoacidosis occurs when there is no carbohydrate substrate and thus no insulin secretion, triggering lipolysis and ketogenesis to prevent hypoglycemia. 13 Patients with lower serum bicarbonate levels are less likely to tolerate oral fluids, 5,14 leading to the belief that acidosis contributes to failure of oral rehydration. Because the administration of carbohydrate substrate limits fatty acid oxidation and ketone production, IV glucose should encourage the resolution of ketosis and acidosis, hastening the tolerance of oral intake and speeding recovery. ...
... 5,15 Children are at increased risk for dehydration 5 and ketosis, due to higher brain energy requirements and lower glycogen stores to produce glucose in times of decreased carbohydrate intake. 13 Acute dehydration thus leads to ketonemia sooner in children than adults (1 day v. 3 days). 13,16 These pathophysiologic features suggest that pediatric patients with dehydration, particularly from vomiting and diarrhea, should be most likely to benefit from IV dextrose. ...
... 13 Acute dehydration thus leads to ketonemia sooner in children than adults (1 day v. 3 days). 13,16 These pathophysiologic features suggest that pediatric patients with dehydration, particularly from vomiting and diarrhea, should be most likely to benefit from IV dextrose. ...
Article
CLINICIAN'S CAPSULE What is known about the topic? Intravenous dextrose halts endogenous ketone production and is commonly recommended in dehydrated patients unable to tolerate oral intake. What did this study ask? Is there evidence that the addition of dextrose to intravenous fluids provides a clinically meaningful benefit in dehydrated patients? What did this study find? Intravenous dextrose has not been shown to provide any important benefit to patients in this setting, but further research is needed. Why does this study matter to clinicians? In dehydrated patients, clinicians should not feel obligated towards dextrose containing solutions, which may be more expensive and less readily available.
... Investigations were carried out to exclude the different causes of her high anion gap metabolic acidosis including lactate, salicylate levels, blood glucose levels, urine (ideally blood ketone metre readings), calcium oxalate crystals on urine microscopy and/or a high osmolar gap (obtained by comparing the patient's measured serum osmolality against predicted osmolality) may suggest ethylene glycol poisoning especially if clinically A Lulsegged, 1 consultant physician, endocrinology and diabetes; E Saeed, 2 foundation year 1, general medicine; E Langford, 2 consultant physician, cardiology; C Duffield, 3 foundation year 1, general surgery; S El-Hasani, 3 ...
... Investigations were carried out to exclude the different causes of her high anion gap metabolic acidosis including lactate, salicylate levels, blood glucose levels, urine (ideally blood ketone metre readings), calcium oxalate crystals on urine microscopy and/or a high osmolar gap (obtained by comparing the patient's measured serum osmolality against predicted osmolality) may suggest ethylene glycol poisoning especially if clinically A Lulsegged, 1 consultant physician, endocrinology and diabetes; E Saeed, 2 foundation year 1, general medicine; E Langford, 2 consultant physician, cardiology; C Duffield, 3 foundation year 1, general surgery; S El-Hasani, 3 ...
... Diabetic ketoacidois is a common cause of metabolic acidosis observed in daily clinical practice. Thus, in the context of a metabolic acidosis involving elevated osmolarity and anion gap, a diagnosis of ketoacidosis due to starvation should be considered in differential diagnosis 1,2 . Metabolic acidosis related to starvation is usually mild, but different factors such as stress could exacerbate it 2 . ...
... Metabolic acidosis related to starvation is usually mild, but different factors such as stress could exacerbate it 2 . During prolonged fasting, insulin secretion is diminished and the systemic response to insulin production is altered [1][2][3] . Diverse metabolic effects resulting from refeeding, are mainly related to alterations in plasma levels of glucose and insulin [4][5][6] . ...
Article
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The present paper presents the first clinical case of a patient suffering from Frutarianism a new "Eating disorder" and severe Ketoacidosis. The life-style feed strictly only on fruits (not even other vegetables, since plant death is necessary previous consumption).This behavioural alteration frequently leads to starvation and the subsequent Ketoacidosis due to starvation.
... This alteration in Bcl-2/Bax ratio occurs due to modulation in the expression of pro-and antiapoptotic Bcl-2 family proteins such as PUMA, Bad, Bim, or Mcl-1, thus altering the response to proapoptotic stimuli. 49,50 Cells die by apoptosis when not needed, especially after pathogen elimination or when injured. 51 Different molecular instructions or stress signals that cells receive internally or externally can activate intrinsic or extrinsic apoptotic signaling pathways. ...
Article
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Cellular starvation occurs when a cell is deprived of nutrition and oxygen availability. The genesis of this state of deprivation is exclusively contingent upon the inadequacy in the supply of essential components, namely amino acids, glucose, and oxygen. Consequently, the impact of this altered condition manifests in the regulation of cellular respiratory, metabolic, and stress responses. Subsequently, as a reactive outcome, cell death may transpire through mechanisms such as autophagy or apoptosis, particularly under prolonged circumstances. However, the cell combats such situations by evolving altered activity in their metabolic and protein level. Modulated signaling cascades help them to conquer starvation. But as in a prolonged condition, the battle that a cell has to evolve will come into and result in the form of cellular death. Therefore, in cancer therapy, cellular starvation may also act as a possible way out so that the cancer cell can undergo its death pathway in an induced starved condition. This review has collectively depicted the mechanism of cellular starvation. Besides this, the cellular response in this starved condition has also been summarized. Gaining such knowledge of the causation of cell starvation and cellular response during starvation not only generates new insight into the mechanism of cell survivability but also may act as a beneficial role in combating cellular diseases like cancer.
... Fasting ketoacidosis is observed in prolonged starvation, pregnancy, postpartum states, lactating women, and while on low-carbohydrate diets. [19][20][21][22] ...
Article
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Euglycemic ketoacidosis (EKA) is a life-threatening emergency seen in diabetic and non-diabetic populations, such as individuals with chronic alcohol ingestion, starvation, pregnancy, and lactating women. More recently, an increasing incidence has been noted with the rising popularity of sodium-glucose cotransporter-2 (SGLT2) inhibitors for treating type 2 diabetes, heart failure, and kidney disease. This condition is characterized by euglycemia to milder degrees of hyperglycemia, metabolic acidosis, and ketonemia. Near-normal glucose levels can often mislead clinicians, resulting in a delayed diagnosis and treatment of this potentially devastating metabolic condition with consequences ranging from hemodynamic instability and electrolyte disturbances to seizures and cerebral edema. The objective of our review is to describe and educate, in detail, all the common etiologies for euglycemic ketoacidosis in diabetic as well as non-diabetic patients.
... Starvation ketoacidosis usually causes mild ketoacidosis which makes this diagnosis less likely. 7 Alcoholic ketoacidosis: unlikely given no reported history of alcohol excess. ...
Article
Euglycaemic diabetic ketoacidosis is a serious but rare adverse effect of treatment with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A man in his 60s with type 2 diabetes mellitus underwent total hip replacement for an intracapsular neck of femur fracture. His SGLT-2 inhibitor was continued perioperatively and blood glucose levels were normal throughout the admission. A diagnosis of severe euglycaemic diabetic ketoacidosis was made in the operating theatre which required treatment in a critical care unit. This resulted in increased morbidity due to decreased postoperative mobilisation and a new requirement for subcutaneous insulin. This case highlights the need for withholding SGLT-2 inhibitors in patients admitted for emergency surgery and a need for regular ketone monitoring in these patients, even in the context of normoglycaemia.
... 3 6 Some previous case reports describe severe SKA in the context of pregnancy, infant intensive care and bariatric surgery complication. [6][7][8] Starvation usually results in decreased levels of cortisol and catecholamines, 3 however stress leads to increased ketogenesis due to raised hormones including catecholamines, cortisol and glucagon. [9][10][11] This man had a mildly raised CRP but marked leucocytosis at admission with peak CRP at day 4 of 336 mg/L and was diagnosed with acute cholecystitis and possible pancreatitis. ...
Article
Starvation ketoacidosis (SKA) is a rarer cause of ketoacidosis. Most patients will only have a mild acidosis, but if exacerbated by stress can result in a severe acidosis. We describe a 66-year-old man admitted with reduced consciousness and found to have a severe metabolic acidosis with raised anion gap. His body mass index (BMI) was noted to be within the healthy range at 23 kg/m ² ; however, it was last documented 1 year previously at 28 kg/m ² with no clear timeframe of weight loss. While his acidosis improved with intravenous fluids, he subsequently developed severe electrolyte imbalance consistent with refeeding during his admission. Awareness of SKA as a cause for high anion gap metabolic acidosis is important and knowledge of management including intravenous fluids, thiamine, dietetic input and electrolyte replacement is vital.
... In a normal healthy individual, short-term starving will only result in mild ketosis. Nonetheless, the effects of ketosis can become more severe if there is a relatively stress and insulin resistance, such as in pregnant or lactating woman or in very young individual such as neonates [1][2][3][4][5]. We report a unique case of severe starvation-induced ketoacidosis in a non-diabetic and non-pregnant patient with a history of multiple recurrent pancreatitis. ...
Article
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Starvation-induced ketoacidosis in non-diabetic and non-pregnant, otherwise healthy patients is not common. In an otherwise normal healthy individual, short-term starving will only result in mild ketosis. Nonetheless, the effects of ketosis can become more severe if there is stress and insulin resistance, such as in pregnant or lactating woman or in very young individual such as neonates. We report a case of severe starvation-induced ketoacidosis in a non-diabetic and non-pregnant 37-year-old African American female patient with a history of multiple recurrent pancreatitis. The patient was initially presented to the emergency department with abdominal pain, nausea and vomiting over two days. The patient also reported starving for two days prior to admission. Biological findings, however, showed a severe degree of metabolic acidosis with an increased anion gap. Serum glucose was normal and 3+ ketonuria were present. Lactic acid was 1.7 mmol/L with no uremia. Salicylate acid, acetaminophen and ethanol level were normal. The patient’s beta-hydroxybutyrate level elevated with ketonuria, suggestive of ketoacidosis as the cause of metabolic acidosis. To our knowledge, the presenting case was novel as no case reports or case series have been reported in these groups of patients. Short-term starvation, if it occurs during periods of stress and medication, may result in life-threatening ketoacidosis, even among non-diabetic women and non-pregnant patients. Awareness of this condition may facilitate prompt recognition and proactive treatment for dietary and stress control.
... The amount of the produced acetyl-CoA may exceed the capacity of the citric acid cycle, resulting in the generation of β-Hydroxybutyrate, acetoacetate, and acetone. [41][42][43][44][45] The proposed mechanism of KA development through Hypoinsulinemic hypoglycemia is reflected in Figure 6. [47] Clearly, all of the above predisposes to ketoacidosis development. ...
Article
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Background: Latest studies have shown the remarkable ability of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce cardiovascular morbidity and mortality. However, real-life data and the results of several other studies seem to contradict these outcomes, pointing out possibilities of serious side effects. Ketoacidosis (KA) remains one of the most dangerous complications, yet, not fully understood. All of the above urgently requires real-practice data, which may shed some light on side effects of this novel anti-diabetic drug family. Aims: To investigate the real-life rates of hypoglycemia and ketosis (K) in SGLT2i treated patients, using Continuous Glucose Monitoring (CGM) and capillary blood β-hydroxybutyrate measurements. Methods: We report the results of a two-year retrospective analysis of 136 Type 2 Diabetes (T2DM) patients, all (100%) treated with SGLT2i, combined with Metformin or Metformin with Incretin-Based therapy (MT-IBT). CGM recordings were done in 52 persons. In 9 patients (Group A), CGM-proved hypoglycemic episodes were discovered. The rest of 43 patients (Group B) didn’t show any hypoglycemia. Three patients in Group A and 11 from Group B were also treated with small doses of basal insulin on admission; the insulin was later discontinued in all patients of Group A and seven patients of Group B. Main characteristics of two groups were subsequently compared. Results: CGM data analysis showed significantly lower average Sensor Glucose (SG), 7.2±1.3 vs. 8.2±1.7 mmol/l, p=0.04, and estimated HbA1c , 6.1±0.7 vs. 6.8±1.1%, p=0.02, in Group A patients. We also report three cases of ketosis, proved by elevated capillary β-hydroxybutyrate concentrations. Pathophysiological link between frequent hypoglycemia rates (Six patients without insulin treatment (11.5 % in total CGM group of 52 patients)) and ketosis development (Three patients (2.2% in total cohort of 136 participants)) was suggested. Conclusions: More frequent than previously reported rates of hypoglycemia and ketoacidosis were discovered in patients taking SGLT2 inhibitors. Pathophysiological link between the two conditions is assumed. More studies are needed to confirm our hypothesis.
... Hence, the reduced muscular mass combined with the fasting state, and the perioperative stress led the ICU consultation team to presume that the patient could have been subject to severe ketosis due to her proneness to rapid depletion of liver and muscle glycogen stores [10]. In fact, starvation and stressinduced acidosis perioperatively and in the ICU setting have previously been described in certain circumstances [11,12], in which several factors in combination can result in moderate or severe ketoacidosis. Repeated episodes of stressinduced ketoacidosis were also reported in an adult patient with SMA type 2, and it was suggested that this metabolic disorder can be easily corrected within hours or few days, provided it is recognized early [13]. ...
Article
Full-text available
Euglycemic ketoacidosis is defined by the triad of high anion gap acidosis, increased plasma ketones, and the absence of hy-perglycemia. Apart from diabetes mellitus, the disorder may occur in prolonged fasting, excessive alcohol consumption, pregnancy, and inborn errors of metabolism. Here, we highlight the diagnosis of euglycemic ketoacidosis in a pediatric non-diabetic patient with spinal muscular atrophy (SMA) type 1 (Werdnig-Hoffmann disease), who, subsequently to her postoperative admission to the intensive care unit following a spinal surgery, developed high anion gap metabolic acidosis. We discuss the pathophysiology of acid-base disorders in SMA, along with the glucose and fatty acids metabolism, the necessary knowledge for medical practitioners.
... Se diagnostica una severa acidosis metabólica con anión gap elevado y cetonas positivas. Manejado con dextrosa 26 . No encontramos ningún caso específico de ayuno prequirúrgico. ...
... The Germ-Terrain duality (GTD) theory is a harmonization of the current Germ Theory (popularized by Louis Pasteur) and the hitherto discarded Terrain Theory (popularized by Pierre Bechamp). The blood's Acid -base balance is affected by physical stress/strain and heat [5][6][7]. ...
... Parenteral glucose terminates starvation ketoacidosis and counteracts the suppressed hepatic gluconeogenesis in MALKA. Accordingly, patients with MALKA seem to benefit primarily from parenteral glucose infusion, reflected in a case report of starvation metabolic acidosis [7] and the management of euglycemic ketoacidosis in pregnancy [4]. Interestingly, new evidence suggests that SGLT2-inhibitors might also cause euglycemic ketoacidosis [8]. ...
Article
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Background In renal failure metformin can lead to lactic acidosis. Additional inhibition of hepatic gluconeogenesis by accumulation of the drug may aggravate fasting-induced ketoacidosis. We report the occurrence of metformin-associated lactic acidosis (MALA) with concurrent euglycemic ketoacidosis (MALKA) in three patients with renal failure. Case presentationsPatient 1: a 78-year-old woman (pH = 6.89, lactic acid 22 mmol/l, serum ketoacids 7.4 mmol/l and blood glucose 63 mg/dl) on metformin and insulin treatment. Patient 2: a 79-year-old woman on metformin treatment (pH = 6.80, lactic acid 14.7 mmol/l, serum ketoacids 6.4 mmol/l and blood glucose 76 mg/dl). Patient 3: a 71-year-old man on metformin, canagliflozin and liraglutide treatment (pH = 7.21, lactic acid 5.9 mmol/l, serum ketoacids 16 mmol/l and blood glucose 150 mg/dl). In all patients, ketoacidosis receded on glucose infusion and renal replacement therapy. Conclusion This case series highlights the parallel occurrence of MALA and euglycemic ketoacidosis, the latter exceeding ketosis due to starvation, suggesting a metformin-triggered inhibition of gluconeogenesis. Affected patients benefit from glucose infusion counteracting suppressed hepatic gluconeogenesis.
... In an otherwise-healthy individual, mild ketosis generally develops after a 12-to 14-hour fast although pH usually remains above 7.3 [4]. However, when combined with physiologic stress or when there is a large glucose requirement, starvation may cause a severe acid-base disturbances [5]. This exaggerated response to fasting has been described in pregnant patients, in the elderly, and in young infants [3,6,7]. ...
Article
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Objective: Unusual clinical course Background: Besides providing anesthesia for surgery, the anesthesiologist’s role is to optimize the patient for surgery and for post-surgical recovery. This involves timely identification and treatment of medical comorbidities and abnormal laboratory values that could complicate the patient’s perioperative course. There are several potential causes of anion and non-anion gap metabolic acidosis in surgical patients, most of which could profoundly affect a patient’s surgical outcome. Thus, the presence of an acute acid-base disturbance requires a thorough workup, the results of which will influence the patient’s anesthetic management. Case Report: An otherwise-healthy 24-year-old female presented for elective spine surgery and was found to have metabolic acidosis, hypotension, and polyuria intraoperatively. Common causes of acute metabolic acidosis were investigated and systematically ruled out, including lactic acidosis, diabetic ketoacidosis, drug-induced ketoacidosis, ingestion of toxic alcohols (e.g., methanol, ethylene glycol), uremia, and acute renal failure. Laboratory workup was remarkable only for elevated serum and urinary ketone levels, believed to be secondary to starvation ketoacidosis. Due to the patient’s unexplained acid-base disturbance, she was kept intubated postoperatively to allow for further workup and management. Conclusions: Starvation ketoacidosis is not widely recognized as a perioperative entity, and it is not well described in the medical literature. Lack of anesthesiologist awareness about this disorder may complicate the differential diagnosis for acute intraoperative metabolic acidosis and lead to a prolonged postoperative stay and an increase in hospital costs. The short- and long-term implications of perioperative ketoacidosis are not well defined and require further investigation.
... Indeed, starvation ketosis causing severe metabolic acidosis is occasionally described in the medical literature and rarely reported in the forensic setting. 1,7,8 This notwithstanding, significantly increased blood ketone body levels can be sporadically observed in forensic casework in situations other than exposure to cold, diabetic or alcoholic ketoacidosis. Though infrequent, these cases do occur and deserve thorough evaluation in order to establish appropriate differential diagnoses and quantify the role that hyperketonemia may play in the death process. ...
Article
Significantly increased blood ketone body levels can be occasionally observed in the forensic setting in situations other than exposure to cold, diabetic or alcoholic ketoacidosis. Though infrequent, these cases do occur and deserve thorough evaluation in order to establish appropriate differential diagnoses and quantify the role that hyperketonemia may play in the death process. Starvation ketoacidosis is a rare cause of metabolic acidosis and is a phenomenon that occurs normally during fasting, as the body switches from carbohydrate to lipid energy sources. The levels of ketonemia in starvation ketoacidosis is usually mild in comparison to those seen in diabetic or alcoholic ketoacidosis. In the clinical setting, several cases of starvation-induced ketoacidosis mainly associated with gastric banding, pregnancy, malnutrition and low-carbohydrate diets have been reported. However, starvation ketosis causing severe metabolic acidosis has been rarely described in the medical literature. In the realm of forensic pathology, starvation-induced hyperketonemia has been rarely described. In this paper we present the postmortem biochemical results observed in situations of suspected starvation-induced hyperketonemia that underwent medico-legal examination. In all these cases, the diagnosis of starvation induced-hyperketonemia and the subsequent ketoacidosis was established per exclusionem based on all postmortem investigation findings. A review of the literature pertaining to the clinical diagnosis of starvation ketoacidosis is also provided.
... Se diagnostica una severa acidosis metabólica con anión gap elevado y cetonas positivas. Manejado con dextrosa 26 . No encontramos ningún caso específico de ayuno prequirúrgico. ...
Article
Full-text available
Objectives To discuss a clinical case and a non-systematic literature review on severe metabolic acidosis due to pre-surgical fasting, its incidence, etiology, and pathophysiology. Materials and methods Discussion of a case of a patient with fasting-induced severe metabolic acidosis during a laparoscopic cholecystectomy, its management and outcomes. The Ethics Committee of our institution approved the case discussion. The literature search included Pub Med, Scielo and Bireme. Results Fasting-induced metabolic acidosis is underdiagnosed and is related to the search for an alternate energy source in the absence of glucose and glycogen. Free fatty acids are these alternate source and generate ketone bodies that accumulate and lead to the development of acidosis. This is the first case of a non-diabetic patient at our institution. We found no other reports at the national level. There are some cases in the world literature associated with fasting from vomiting during the third trimester of pregnancy, psychiatric disorders, strict dieting, gastric band dysfunction and alcohol abuse Conclusions The anesthesiologist must be aware of this possibility in patients with fasting induced metabolic acidosis with normal lactate values and hemodynamic impairment that are either too young or too old, non-diabetic and with no history of alcohol abuse. The anion gap calculation tool is a simple diagnostic approach. The incidence of the condition increases during pregnancy.
... 11 The acidosis produced is generally mild, 12 but there are case reports of a more severe acidosis when starvation is combined with other forms of physiological stress, such as infection and dehydration in a postpartum woman 13 and in a paediatric patient with hypoxic brain injury. 9 Ketoacidosis is the result of production of ketones by the liver, a clinical picture recognised most commonly in the setting of insulin deficiency and hyperglycaemia of diabetes. In that situation, hypoinsulinaemia promotes lipolysis of peripheral fat stores and stimulates the production of ketones, which are derived from the partial oxidation of free fatty acids in the liver. ...
... Acute starvation does not typically lead to acidosis because of the presence of insulin. Stress may also worsen starvation ketoacidosis [1]. ...
Article
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A 36 year-old 5 weeks postpartum lactating woman presented to the emergency room with severe nausea and vomiting for 48 hours. The patient was found to be in non-diabetic ketoacidosis with a serum pH 6.9 and a HCO3 of <5mEq/L. This condition rapidly improved with the administration of intravenous dextrose and bicarbonate and with the cessation of breast feeding. The course and pathophysiology of the rarely described phenomenon of bovine ketosis in a human is discussed here.
Article
Introduction: In case of failure of oral rehydration, children with acute gastroenteritis can be hydrated using intravenous (IV) solution. The choice of the intravenous solution itself (solutions containing dextrose versus crystalloids alone) and the glucose quantities to administer are not well established. Objectives: The main objective of this study was to evaluate the association between the amount of intravenous glucose provided and hospitalization for children with acute gastroenteritis. Another objective was to evaluate practice variation regarding the amount of glucose provided for IV rehydration in a pediatric emergency department (ED). Method: We conducted a retrospective cohort study from 2019 to 2022 in a Canadian pediatric ED. We included children with acute gastroenteritis undergoing IV rehydration. Patient with hypoglycemia, metabolic disease, or diabetes were excluded. The IV glucose administered during the initial 4 hours of rehydration was quantified. The primary outcome was hospitalization, and return visit within the following week was a secondary outcome. Ten percent of the charts were evaluated in duplicate to assess interrater reliability. We examined glucose distribution at 1 and 4 hours and utilized multiple logistic regression to relate glucose amounts with hospitalization and second visit, accounting for age, weight, bicarbonate levels, ondansetron use, and amount of liquid infused. It was estimated that the evaluation of 250 cases would have at least 50 admissions. Results: Among 6939 children evaluated for potential acute gastroenteritis, 250 met our inclusion/exclusion criteria. All variables included in the analysis had excellent interrater reliability. Notable variations existed in glucose quantities provided, both at 1 hour (first quartile, 87 mg/kg; third quartile, 294 mg/kg) and 4 hours (first quartile, 681 mg/kg; third quartile, 1174 mg/kg) of rehydration. Multiple logistic regression showed a negative association between hospitalization and glucose administration during the initial hour (OR for each 100 mg/kg increment, 0.60; 95% CI, 0.42-0.84) and 4 hours (OR, 0.76; 95% CI, 0.63-0.91) of rehydration. Moreover, children who received more dextrose during the first hour of rehydration were less likely of having a return visit (OR for each 100 mg/kg increment: 0.52; 95% CI, 0.35-0.78), as well as during the first 4 hours (OR for each 100 mg/kg increment, 0.83; 95% CI, 0.73-0.94). Conclusions: There was a wide practice variation in intravenous glucose provided to children with acute gastroenteritis. In this population, higher intravenous glucose amount was associated to a lower risk of hospitalization and lower risk of return visit.
Article
Background Our bodies have adaptive mechanisms to fasting, in which glycogen stored in the liver and muscle protein are broken down, but also lipid mobilisation is triggered. As a result, glycerol and fatty acids are released into the bloodstream, increasing the production of ketone bodies in liver. However, there are limited studies on the incidence of perioperative urinary ketosis, the intraoperative blood glucose changes and metabolic acidosis after fasting for surgery in non‐diabetic adult patients. Methods We conducted a retrospective cohort study involving 1831 patients undergoing gynecologic surgery under general anesthesia from January to December 2022. Ketosis was assessed using a postoperative urine test, while blood glucose levels and acid–base status were collected from intraoperative arterial blood gas analyses. Results Of 1535 patients who underwent postoperative urinalysis, 912 (59.4%) patients had ketonuria. Patients with ketonuria were younger, had lower body mass index, and had fewer comorbidities than those without ketonuria. After adjustments, younger age, higher body mass index and surgery starting late afternoon were significant risk factors for postoperative ketonuria. Of the 929 patients assessed with intraoperative arterial blood gas analyses, 29.0% showed metabolic acidosis. Multivariable logistic regression revealed that perioperative ketonuria and prolonged surgery significantly increased the risk for moderate‐to‐severe metabolic acidosis. Conclusion Perioperative urinary ketosis and intraoperative metabolic acidosis are common in patients undergoing gynecologic surgery, even with short‐term preoperative fasting. The risks are notably higher in younger patients with lower body mass index. Optimization of preoperative fasting strategies including implementation of oral carbohydrate loading should be considered for reducing perioperative metabolic derangement due to ketosis.
Article
Diabetic ketoacidosis is defined as hyperglycemia >250 mg/dL with metabolic acidosis of arterial pH <7.3, serum bicarbonate <18 mEq/L with positive urine and serum ketones and an anion gap >10. Euglycemic ketoacidosis has been reported in patients with type 2 diabetes and in patients with type 1 diabetes. However, as a surgical complication, euglycemic ketoacidosis has not been reported. We report 2 cases from 2 teaching tertiary care centers of patients with type 2 diabetes who developed high‐gap ketoacidosis in an intensive care unit while recovering from emergent abdominal surgery. Both patients developed altered mental status, metabolic acidosis with a bicarbonate level as low as 14 mEq/L, and an anion gap > 18, without hyperglycemia. Both patients had β‐hydroxybutyrate levels > 5 mmol/L.
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Prepare your students for their future careers with Essentials of Pathophysiology: Concepts of Altered Health States, 4/e. This clear, readable, and student-friendly text delivers "need to know" disease content, along with the essential foundation in science that nursing, physician assistant, pharmacology, advanced health science, and medical students need to succeed in their future careers. Approaching the topic as an exploration of pathophysiology, the book relates normal body functioning to the physiologic changes that occur as a result of disease and provides concise yet complete coverage of how the body works. The Fourth Edition builds on the book's extremely successful art program and the "Understanding" feature and incorporates summary concept boxes after each section. In addition, an expanded, robust, and flexible suite of supplements, including a Study Guide, over 40 advanced 3-D animations, prepU, and Lippincott's CoursePoint, provide students with all the tools they need to succeed. Student Resources: • Learning Objectives for each chapter provide an outline of key content that must be mastered. • Journal Articles by chapter, updated for this edition, offer access to current research available in LWW journals. • Concepts in Action Animations for every chapter help students master key topics. • New! More than 40 Advanced, 3-D Narrated Animations help students master complex athophysiological concepts. • A Spanish-English Audio Glossary provides terms and phrases for communicating with patients in Spanish. • Monographs of the most commonly prescribed drugs provide up-to-date information. • 600 NCLEX-style Review Questions help students improve their test-taking skills and prepare for the NCLEX. • A Dosage Calculations Question & Review Question Bank gives students practice in math skills and calculating drug dosages and reinforce key topics of the course. Instructor Resources: • PowerPoint presentations make it easy for you to integrate the textbook with your students' classroom experience, via either handouts or slide shows. • Guided Lecture Notes walk you through the chapters, objective by objective, and provide corresponding PowerPoint numbers. • Discussion Topics (and suggested answers) can be used as a conversation starter or in online discussion boards. • Assignments (and suggested answers) include group, written, clinical, and Web assignments. • Case Studies (with related questions and suggested answers) give your students an opportunity to apply their knowledge to a client case similar to what they will encounter in practice. • Journal Articles, updated for this edition, offer access to research available in LWW journals. • Answers to Review Exercises in the Book are provided for your convenience. • Pre-Lecture Quizzes (and answers) are quick, knowledge-based assessments that allow you to check students' reading. • Learning Objectives for each chapter allow you to assess your students' mastery of key skills. • A QSEN Map demonstrates how the text supports QSEN competencies and their relationship to excellent clinical practice. • A Sample Syllabus provides guidance for structuring your course. • Concepts in Action Animations and Advanced 3-D Narrated Animations are provided to enhance your lectures. To further support your course, the Fourth Edition is accompanied by a Study Guide, prepU, and new to this edition, Lippincott CoursePoint, a digital curriculum solution that integrates adaptive learning powered by prepU with access to personalized, perfectly timed remediation built on trusted content. Each product in the suite can be purchased separately or packaged with the main text.
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Non-fibrillatory cardiac arrest is a term used to encompass the defined cardiac arrest rhythms, pulseless electrical activity (PEA) and asystole, arrest rhythms that are distinct from ventricular fibrillation or pulseless ventricular tachycardia. Until recently, the term electromechanical dissociation (EMD) was used in place of PEA. EMD was defined as the presence of electrical complexes without accompanying mechanical contractions of the heart. Several studies have demonstrated that often during EMD arrest there actually is mechanical cardiac activity associated with the electrical complexes seen on a cardiac monitor. PEA, defined as organized electrical activity with the absence of clinically detectable pulses, is thus a physiologically more appropriate terminology. Patients in asystole, by definition, have no discernible ventricular activity by electrocardiography or ultrasonography, and no associated perfusion. This chapter will focus on the diagnosis and treatment of PEA subsets. The incidence of PEA during cardiac arrest appears to be changing. Prior to 1990, PEA was reported to be the initial presenting rhythm in approximately 20% of hospitalized patients who are monitored at the onset of cardiac arrest and 16.5% of patients who present to a prehospital system in cardiac arrest. Several recent studies have reported the incidence of PEA to be 35%-40% of all in-hospital resuscitation events. Data from the Ontario province advanced life support (OPALS) study found over a 4-year study period an increasing PEA incidence of 19.9% to 24.5%, with a coexisting shortened EMS system response time.8 The OPALS group further demonstrated a 50.1% incidence of PEA arrests in the subgroup of patients that arrested after the arrival of EMS. © Norman A. Paradis, Henry R. Halperin, Karl B. Kern, Volker Wenzel and Douglas A. Chamberlain 2007 and Cambridge University Press 2009.
Article
Ketoacidosis is a life threatening condition usually caused by diabetes mellitus or alcohol. In this case report we present a lactating woman who developed a severe ketoacidosis a few weeks post partum. Her nutritional status was inadequate due to illness and a diet low on carbohydrates. Five case reports regarding ketoacidosis in lactating women have previously been described in the literature. This case report highlights the importance of nutrition during periods of breast feeding.
Article
Objetivos Presentación de un caso clínico y revisión no sistemática de la literatura sobre acidosis metabólica severa por ayuno prequirúrgico, su incidencia, etiología y fisiopatología. Materiales y métodos Con autorización del Comité de Ética de nuestra institución, se presenta el caso de un paciente con acidosis metabólica severa inducida por ayuno durante una colecistectomía laparoscópica, su manejo y desenlace. La búsqueda bibliográfica se realizó en PubMed, Scielo y Bireme. Resultados La acidosis metabólica secundaria a ayuno es subdiagnosticada y está relacionada con la búsqueda de una fuente alterna de energía en ausencia de glucosa y glucógeno. Los ácidos grasos libres constituyen esta alternativa, generando cuerpos cetónicos que, al acumularse, desencadenan una cetoacidosis. Este el primer caso en nuestra institución en un paciente no diabético. No encontramos reportes a nivel nacional. Existen en la literatura médica mundial casos asociados a ayuno secundarios a vómito durante el tercer trimestre de embarazo, trastornos psiquiátricos, dietas estrictas, disfunción de banda gástrica y abuso de alcohol. Conclusiones El anestesiólogo debe contemplar esta posibilidad en pacientes con acidosis metabólica inducida por ayuno con valores de lactato normal y clínica de deterioro hemodinámico, que estén en los extremos de la vida, no diabéticos ni con antecedentes de abuso de alcohol. El cálculo de anión gap es una herramienta sencilla de aproximación diagnóstica. Su incidencia aumenta durante el embarazo.
Article
The present paper presents the firts clinical case of a patient suffering from Frutarianism a new "Eating disorder" and severe Ketoacidosis. The life-style feed strictly only on fruits (not even other vegetables, since plant death is necessary previous consumption).This behavioural alteration frequently leads to starvation and the subsequent Ketoacidosis due to starvation.
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We herein report an autopsy case involving a 27-year-old Caucasian woman suffering from chronic adrenocortical insufficiency with a background of a polyendocrine disorder. Postmortem biochemistry revealed pathologically decreased aldosterone, cortisol, and dehydroepiandrosterone levels in postmortem serum from femoral blood as well as decreased cortisol and 17-hydroxycorticosteroid in urine. Decreased vitreous sodium and increased 3-beta-hydroxybutyrate and C-reactive protein concentrations were observed. The cause of death was determined to be acute adrenocortical insufficiency. Fasting ketoacidosis was postulated to have precipitated the Addisonian crisis. Traumatic causes of death and third-party involvement were excluded. The case highlights the importance of systematically performing exhaustive postmortem biochemical investigations to formulate appropriate hypothesis regarding the pathophysiological mechanisms involved in the death process.
Article
Ketoacidotic syndromes are frequently encountered in acute care medicine. This article focuses on ketosis and ketoacidotic syndromes associated with intoxications, alcohol abuse, starvation, and certain dietary supplements as well as inborn errors of metabolism. Although all of these various processes are characterized by the accumulation of ketone bodies and metabolic acidosis, there are differences in the mechanisms, clinical presentations, and principles of therapy for these heterogeneous disorders. Pathophysiologic mechanisms that account for these disorders are presented, as well as guidance regarding identification and management.
Article
Lactation ketosis is a recognised disorder in postpartum lactating cows where a negative energy balance develops because the energy demands of milk production exceed the energy capacity of the animal. Rarely, nursing women can develop problems with lactation ketosis when their glycogen stores are depleted, causing the body to turn to gluconeogenesis as an energy substrate for galactopoiesis. The authors describe the case of a breastfeeding woman admitted to hospital and made nil per os (NPO) to treat a bowel obstruction. She did not receive intravenous glucose and 3 days postadmission developed a dangerous starvation ketosis (venous pH of 6.64). She was treated with intravenous dextrose, bicarbonate as well as cessation of breastfeeding and recovered quickly. Only four previous reports describe human lactation ketosis and this is the first iatrogenic case reported to our knowledge. It highlights the importance of addressing the unique caloric requirements of nursing women, especially when they are kept NPO.
Article
A previously healthy boy was admitted with fever, tachycardia, dyspnea, and was vomiting. A blood test showed a severe metabolic acidosis with pH 7.08 and an anion gap of 36 mmol/L. His urine had an odor of acetone. The serum glucose was 5.6 mmol/L, and no glucosuria was found. Diabetic ketoacidosis could therefore be eliminated. Lactate level was normal. Tests for the most common metabolic diseases were negative. Because of herpes stomatitis, the boy had lost appetite and only been drinking Diet Coke and water the last days. Diet Coke or Coca-Cola Light is sweetened with a blend containing cyclamates, aspartame, and acesulfame potassium, all free of calories. The etiology of the metabolic acidosis appeared to be a catabolic situation exaggerated by fasting with no intake of calories. The elevated anion gap was due to a severe starvation ketoacidosis, mimicking a diabetic ketoacidosis. Pediatricians should recommend carbohydrate/calorie-containing fluids for rehydration of children with acute fever, diarrhea, or illness.
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Data from 191 post-mortem cases where post-mortem blood beta-hydroxybutyrate (βHB) and acetone concentrations and vitreous humor glucose concentrations (where available) had been measured were retrospectively investigated to determine the markers required to identify and distinguish between Alcoholic Ketoacidosis (AKA), Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS). Blood βHB concentrations above 250 μg/mL were considered significant and it was shown to be the preferred marker of ketoacidosis. All cases with significant βHB detected also had acetone present (greater than 2mg/dL) demonstrating that acetone can be used as a marker to identify ketoacidosis and can be used to indicate when βHB measurement is necessary. Vitreous humor glucose concentrations above 6.9 mmol/L were considered high and indicative of hyperglycemia prior to death. Vitreous humor glucose concentrations can be used to distinguish between DKA and ketoacidosis from other causes and to identify deaths due to HHS. The data showed that ketoacidosis can occur without a history of alcoholism or diabetes. Many diabetics are undiagnosed for many years. Therefore, DKA or HHS should be considered in sudden or unexplained deaths and glucose should be routinely measured especially in cases with risk factors for diabetes including obesity, old age, a history of mental health problems or treatment with atypical antipsychotic drugs including clozapine, olanzapine, quetiapine and risperidone.
Article
Altered level of consciousness describes the reason for 3% of critical emergency department (ED) visits. Approximately 85% will be found to have a metabolic or systemic cause. Early laboratory studies such as a bedside glucose test, serum electrolytes, or a urine dipstick test often direct the ED provider toward endocrine or metabolic causes. This article examines common endocrine and metabolic causes of altered mentation in the ED via sections dedicated to endocrine-, electrolyte-, metabolic acidosis-, and metabolism-related causes.
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Although the presence and etiology of a metabolic acidosis in a tachypnic, dehydrated patient with a sweet odor on his or her breath and complaints of vomiting and polyuria is obvious, the physician is rarely so fortunate. More often, a metabolic acidosis must be confirmed by means of a simultaneous arterial blood gas and an electrolyte panel. Serum anion gap must be calculated to differentiate between an elevated gap and normal gap acidosis. The applicable mnemonic must be recalled, and each etiology examined and considered or rejected as a possibility in the given clinical scenario. As in nearly every etiology discussed in this article, the key to diagnosis can be found with a careful history and a high index of suspicion for toxic exposure.
Article
A 35-year-old postpartum lactating woman presented with dyspnea and was found to be in non-diabetic ketoacidosis (pH 7.24, HCO3 10 mmol/L, urine ketones >80 mg/dL). Rapid clinical and laboratory resolution occurred after intravenous dextrose and enteral feeding along with discontinuation of lactation. This represents a rarely reported case of lactation "bovine" ketoacidosis in humans. We review the historical precedence for the diagnosis and detail the underlying physiology. (C) 2008 Elsevier Inc.
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We evaluated the use of the urinary anion gap (sodium plus potassium minus chloride) in assessing hyperchloremic metabolic acidosis in 38 patients with altered distal urinary acidification and in 8 patients with diarrhea. In seven normal subjects given ammonium chloride for three days, the anion gap was negative (-27 +/- 9.8 mmol per liter) and the urinary pH under 5.3 (4.9 +/- 0.03). In the eight patients with diarrhea the anion gap was also negative (-20 +/- 5.7 mmol per liter), even though the urinary pH was above 5.3 (5.64 +/- 0.14). In contrast, the anion gap was positive in all patients with altered urinary acidification, who were classified as having classic renal tubular acidosis (23 +/- 4.1 mmol per liter, 11 patients), hyperkalemic distal renal tubular acidosis (30 +/- 4.2, 12 patients), or selective aldosterone deficiency (39 +/- 4.2, 15 patients). When the data on all subjects studied were pooled, a negative correlation was found between the urinary ammonium level and the urinary anion gap. We conclude that the use of the urinary anion gap, as a rough index of urinary ammonium, may be helpful in the initial evaluation of hyperchloremic metabolic acidosis. A negative anion gap suggests gastrointestinal loss of bicarbonate, whereas a positive anion gap suggests the presence of altered distal urinary acidification.
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The development of diabetic ketoacidosis (DKA) involves a series of closely interrelated derangements of intermediary metabolism and of body fluid volume and composition whose fundamental nature has not been completely unraveled [1–8]. The composite clinical picture in full-blown DKA on admission includes hyperglycemia with hyperosmolality, metabolic acidosis due to the accumulation of ketoacids, extracellular and intracellular fluid (ECF and ICF, respectively) volume depletion, and varying degrees of electrolyte deficiency, particularly of potassium and phosphate [9–11]. Since proper correction of the alterations in volume status, acid-base, and electrolyte composition is critical for survival, a clear understanding of the pathogenesis of these derangements is essential for the adequate management of DKA. The present review will focus on the role of the kidney in the pathogenesis of the different patterns of electrolyte and acid-base composition observed on admission for and during recovery from DKA. Special emphasis will be placed on the role of the kidney in the defense of acid-base homeostasis during the recovery phase. Other aspects of the alterations that develop in DKA have been reviewed in detail elsewhere [12–14].
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Intensive efforts are presently directed toward developing pharmacologic therapy to protect the ischemic brain. Preclinical data from animal models indicate that insulin, already available for human use, may reduce damage in both global and focal ischemia. Two kinds of mechanisms may be involved: one in which insulin interacts directly with brain tissue and one in which insulin acts indirectly by reducing peripheral blood glucose levels. Animal data indicate that part of the former, direct mechanism is mediated by insulin-like growth factor-1 receptors. The direct effect appears to predominate in global ischemia. In focal ischemia, unlike global ischemia, the effect of insulin is predominantly via peripheral hypoglycemia, because neuroprotection is largely annulled by co-administration of glucose. The two clinical counterparts of global and focal ischemic models are, respectively, cardiac arrest encephalopathy and focal ischemic stroke. Insulin use in both of these clinical situations could be evaluated in clinical trials that attempt to reduce ischemic brain damage, because insulin has a long and safe history of human use in diabetes treatment.
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Ischemic stroke is a leading cause of death and long-term disability, and hyperglycemia is believed to aggravate cerebral ischemia. To review animal and human studies on the relationship between hyperglycemia and brain ischemia that elucidate some of the mechanisms for the deleterious effect of hyperglycemia. To discuss present and future clinical recommendations for glucose control. Computerized data sources and published indexes and articles from 1976 through 2000 were searched for human studies that evaluated the association between stroke and hyperglycemia, and studies focused on experimental models of hyperglycemic animals with focal and global brain ischemia. Most human studies have shown that in acute stroke, admission hyperglycemia in patients with or without diabetes is associated with a worse clinical outcome than in patients without hyperglycemia. This association is more consistent in the nonlacunar type of stroke. Animal studies support these findings by showing both in global and in focal postischemic models that hyperglycemia exaggerates the following damaging processes: intracellular acidosis, accumulation of extracellular glutamate, brain edema formation, blood-brain barrier disruption, and tendency for hemorrhagic transformation. Insulin treatment of hyperglycemic animals was found to have a beneficial effect in focal and global brain ischemia, which may be mediated by the glucose-reduction effect or by a direct neuroprotection. Most studies show the deleterious effect of early hyperglycemia, especially in patients with nonlacunar focal or global ischemia. Clinical trials of intensive insulin treatment are needed. Meanwhile simple measures to avoid excessive hyperglycemia are recommended.
Article
Objective.— To review limitations of the use of serum anion gap in clinical practice.Data Sources.— Original reports and reviews.Study Selection.— Sources containing the most recent pertinent information.Data Synthesis.— Theoretical and practical limitations beset the use of serum anion gap. Awareness of these limitations reduces but does not eliminate wrong diagnoses based on the anion gaps.Conclusions.— Serum anion gap has a limited value in the differential diagnosis of acid-base disorders and can be misleading.(Arch Intern Med. 1992;152:1625-1629)
Article
• Using modern electrode technology (Beckman ASTRA analyzer), we evaluated the reference range for the anion gap (calculated as sodium minus chloride minus bicarbonate concentrations) in serum to determine whether the 8 to 16 mmol/L reference range in common use is still valid. After measurement of electrolytes in (1) serum from 29 healthy volunteers, (2) aqueous standards verified against National Bureau of Standards reference material, and (3) serum from 120 blood donors, we drew the following conclusions. (1) The reference range for the anion gap has shifted downward (to 3 to 11 mmol/L in one of our laboratories), primarily because of an upward shift in chloride values. (2) Using the ASTRA analyzer, a majority of normal individuals can be expected to have serum anion gaps of 6 mmol/L or less unless chloride calibration is deliberately altered. (3) If the anion gap is to remain an effective tool in diagnosing acid-base disorders, clinicians need to be aware that the traditional reference range may not be appropriate with new instrumentation. (Arch Intern Med. 1990;150:311-313)
Article
We have studied 35 patients to find the occurrence of hyperchloremic acidosis during the recovery phase of diabetic ketoacidosis. At admission the patients had typical normochloremic acidosis, with increased anion gap exactly balancing decreased serum bicarbonate. In contrast, in 18 patients with phenformin-induced lactic acidosis, the increase in anion gap at admission was much greater than the decrease in bicarbonate. The difference between lactic acidosis and ketoacidosis may be explained by a slower rate of excretion of lactate than of ketone anions. After the patients with ketoacidosis were treated, the acidosis became predominantly hyperchloremic with normal anion gap. Failure to normalize serum bicarbonate is attributed to excretion of ketone anions in the urine.
Article
Previous studies have attributed norepinephrine's ketogenic activity to its ability to mobilize peripheral fat stores. This study was designed to determine whether norepinephrine has ketogenic activity independent of its lipolytic effect in diabetic man. Six insulin-dependent diabetic subjects were infused with pathophysiologic concentrations of norepinephrine (0.08 μg./kg./ min.). As a control for norepinephrine's lipolytic effect, a separate heparin-induced free fatty acid generation study was performed on each subject. The results demonstrate, for the first time in man, that norepinephrine has ketogenic activity independent of its lipolytic effect. Furthermore; physiologic elevations of norepinephrine concentration were also demonstrated to increase plasma glucagon concentration. Our data are consistent with the possibility that the rise in concentration of glucagon may have a participated in the catecholamine-augmented ketogenesis.
Article
The anion gap can be readily calculated from routine laboratory data, and although it has its widest application in the diagnosis of various forms of metabolic acidosis, it may sometimes provide an important clue to the diagnosis of disorders such as multiple myeloma or bromide intoxication. However, the concept of the anion gap is often misunderstood and misapplied. The purpose of this communication is to discuss in some detail the concept of the anion gap, the implications of abnormalities of the anion gap and, finally, its application to the differential diagnosis of metabolic acidosis.
Article
Hyperglycemia is known to aggravate ischemic brain damage. This study sought to determine if preischemic insulin-induced normoglycemia would improve outcome in hyperglycemic rats. Normal rats and rats with 5-7 days of streptozotocin-induced diabetes were studied. Normal rats served as either fasted normoglycemic controls or dextrose-infused (hyperglycemic) controls. In the acutely diabetic rats either no insulin was given or insulin was given at 30 or 90 minutes before ischemia so as to induce preischemic normoglycemia. All rats underwent 10 minutes of forebrain ischemia. After 5 days of recovery, motor function and histological outcome were assessed. Untreated diabetic rats and dextrose-infused control rats had greater hippocampal CA1 damage than normoglycemic control rats. In contrast, insulin-treated diabetic rats had less hippocampal CA1 damage than either untreated diabetic rats or dextrose-infused control rats. Injury in the two insulin-treated groups was not significantly different from that in the normoglycemic control group (all three groups had plasma glucose values of 120-150 mg/dl immediately prior to ischemia). Despite similar plasma glucose values (300-400 mg/dl), fewer postischemic seizures (0% versus 67%) were observed in the untreated diabetic group than in the dextrose-infused control group (p < 0.001). Hyperglycemia caused by either dextrose infusion or streptozotocin-induced diabetes resulted in exacerbated ischemic brain damage. Insulin therapy to rapidly induce preischemic normoglycemia improved outcome from forebrain ischemia in the acutely diabetic rats. Glucose-infused hyperglycemic rats frequently exhibited postischemic generalized seizures while acutely diabetic rats did not. The latter results implicate some adaptive/protective mechanism associated with acute streptozotocin-induced diabetes that results in a decreased sensitivity to hyperglycemia-augmented ischemic brain damage.
Article
Objective.-To review limitations of the use of serum anion gap in dinical practice. Data Sources.-Original reports and reviews. Study Selection.-Sources containing the most recent pertinent information. Data Synthesis.-Theoretical and practical limitations beset the use of serum anion gap. Awareness of these limitations reduces but does not eliminate wrong diagnoses based on the anion gaps. Conclusions-Serum anion gap has a limited value in the differential diagnosis of acid-base disorders and can be misleading.
Article
A case of severe starvation ketoacidosis developing during pregnancy is presented. The insulinopenic/insulin-resistant state found during fasting in late gestation predisposes to ketosis. Superimposition of stress hormones, which further augment lipolysis, exacerbates the degree of ketoacidosis. In our patient, gestational diabetes, twin pregnancies, preterm labor, and occult infection were factors that contributed to severe starvation ketoacidosis. Diagnosis was delayed because starvation ketosis is not generally considered to be a cause of severe acidosis, and because the anion gap was not elevated. Improved understanding of the complex fuel metabolism during pregnancy should aid in prevention, early recognition, and appropriate therapy of this condition.
Article
Pediatricians often tell parents to give their children clear liquids for hydration during acute gastroenteritis. Since the release of aspartame (Nutrasweet) in 1981, the composition of some clear liquids for hydration of children has changed. Although 12 ounces of sucrose-sweetened carbonated beverage contains about 100 calories, the same volume of aspartame-sweetened beverage contains about one calorie. Therefore, using aspartame-sweetened beverage to support hydration in children with diarrhea theoretically increases the potential for a starvation state to develop. A case of oral rehydration associated with starvation ketosis is described. CASE HISTORY In the 3 weeks preceding admission, a 5-year-old boy had been treated with oral cephalexin (Keflex) for a knee infection (septic arthritis vs cellulitis).
Article
Diabetic ketoacidosis may occur in women treated with intravenous beta-sympathomimetic agents for tocolysis. We describe diabetic ketoacidosis and transient severe insulin resistance in a woman with diabetes who was treated with subcutaneous terbutaline infusion. Subcutaneous terbutaline infusion may precipitate transient insulin resistance and diabetic ketoacidosis in women with diabetes.
Article
Using modern electrode technology (Beckman ASTRA analyzer), we evaluated the reference range for the anion gap (calculated as sodium minus chloride minus bicarbonate concentrations) in serum to determine whether the 8 to 16 mmol/L reference range in common use is still valid. After measurement of electrolytes in (1) serum from 29 healthy volunteers, (2) aqueous standards verified against National Bureau of Standards reference material, and (3) serum from 120 blood donors, we drew the following conclusions. (1) The reference range for the anion gap has shifted downward (to 3 to 11 mmol/L in one of our laboratories), primarily because of an upward shift in chloride values. (2) Using the ASTRA analyzer, a majority of normal individuals can be expected to have serum anion gaps of 6 mmol/L or less unless chloride calibration is deliberately altered. (3) If the anion gap is to remain an effective tool in diagnosing acid-base disorders, clinicians need to be aware that the traditional reference range may not be appropriate with new instrumentation.
Article
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
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Use of dextrose in intravenous resuscitation fluids is common practice; however, this study indicates that 5% dextrose solutions, even if administered in physiologic quantities, greatly worsens the outcome of survivable cardiac arrest. Twelve adult male mongrel dogs were premedicated with morphine, anesthetized with halothane, instrumented, intubated, and ventilated. Each dog was first given 500 ml of either lactated Ringer's (LR) (n = 6) or 5% dextrose in LR (D5LR) (n = 6). Halothane was stopped and fibrillation was induced (60 Hz). Blood glucose just before cardiac arrest was 129 mg/dl in the LR dogs and was increased to 335 mg/dl in the D5LR dogs. After eight minutes of arrest, resuscitation, including internal cardiac massage and standard advanced cardiac life support drug protocols (modified for dogs), was begun. When stable cardiac rhythm was obtained, the chest was closed, and LR or D5LR continued until a total of 1L was given. A neurologic score (0 = normal to 100 = dead) was assigned at 1, 2, 6, and 24 hours. The LR group did not differ statistically from the D5LR group in operative time, number of defibrillatory shocks, time to spontaneous ventilation, time to extubation, or drugs required. Resuscitation was successful in all six LR and five of six D5LR group; however, by 2 hours after resuscitation and thereafter, D5LR group had a significantly greater neurologic deficit (p less than 0.05) than did the LR group. By 9 hours, four of six D5LR dogs displayed convulsive activity and died. At 24 hours the D5LR group had a greater (p less than 0.008) neurologic deficit (82 +/- 11) than did the LR group (21 +/- 7), which walked and ate. We conclude that the addition of 5% dextrose to standard intravenous fluids greatly increases the morbidity and mortality associated with cardiac resuscitation.
Article
In a previous study of starvation-induced acute ketoacidosis, net ketoacid production was inhibited by acid and facilitated by base ingestion. To determine whether hydrogen ion modifies net ketoacid production during chronic ketoacidosis, six over-weight volunteers ingested NaHCO3, NaCl, or NH4Cl (2 mmol X kg-1 X day-1), each for 7 days, during weeks 6-8 of ketogenic dieting. During days 4-7 of each phase, blood bicarbonate was stable but lower in the NH4Cl (19.6 +/- 0.7 mM) than the NaHCO3 (23.7 +/- 0.7 mM) phases. Throughout these periods, acid intake differed by 216 mmol/day, whereas acid output differed by 129 mmol/day between the NaHCO3 and the NH4Cl phases. The major contribution to this difference in acid balance was a difference in net organic acid (ketoacid) production. Although blood ketones were stable, ketoacid excretion, reflecting net ketoacid production, was decreased by 59% with acid and increased by 66% with base compared with NaCl (control) ingestion. Thus, in this state of chronic ketoacidosis, challenges to acid-base balance were countered by a rapidly occurring, sustained, reversible, and quantitatively significant modification of net acid production which acted as an effective mechanism for acid-base regulation.
Article
Hypermetabolism characterizes the metabolic response to thermal injury and the extent of energy production is positively related to the rate of urinary catecholamine excretion. Alpha and beta adrenergic blockade decreased metabolism from 69.6 +/- 5.3 Kcal/m(2)/hr to 57.4 +/- 5.2 (p < 0.01), and infusion of 6 microgm epinephrine/minute in normal man significantly increased metabolic rate. Twenty noninfected burned adults with a mean burn size of 45% total body surface (range 7-84%) and four normal controls were studied in an environmental chamber at two or more temperatures between 19 and 33 C with vapor pressure constant at 11.88 mm Hg. All burn patients were hypermetabolic at all temperatures studied and their core and mean skin temperatures were significantly elevated above control values. Between 25 and 33 C ambient, metabolism was unchanged in controls and burns of less than 40% total body surface (48.9 +/- 4.6 Kcal/m(2)/hr vs. 48.9 +/- 4.5), but metabolic rate decreased in larger burns in the warmer environment (72.0 +/- 1.9 vs. 65.8 +/- 1.7, p < 0.001). At 21 C, metabolism and catecholamines increased, except in four nonsurvivors who became hypothermic with decreased catechol elaboration. Metabolic rate in ten patients with bacteremia was below predicted levels while catecholamines were markedly elevated suggesting interference with tissue uptake of the neurohormonal transmitters. Feeding burn patients or administering glucose and insulin improved nitrogen retention and altered substrate flow but did not significantly reduce urinary catecholamines or metabolic rate. Burned patients are internally warm, not externally cold, and catecholamines appear to mediate their increased heat production. Hypermetabolism may be modified by ambient temperature, infection, and pharmacologic means. Alterations in hypothalamic function due to injury, resulting in increased catecholamine elaboration, would explain the metabolic response to thermal injury.
Article
In women fasted during the second trimester of pregnancy, concentrations of glucose and insulin in the plasma fell to a greater extent and ketone acid concentrations in the blood rose more rapidly than in nonpregnant controls. Nitrogen excretion in the urine, particularly ammonia, was increased in the pregnant group. Continuous glucose utilization by the conceptus may exaggerate and accelerate the metabolic consequences of starvation.
Article
Usually, ketoacidosis presents few if any diagnostic or therapeutic problems; in this article, we report a case where ketoacidosis was clinically occult and biochemically obscure. The patient presented with acute pancreatitis associated with a modest antecedent alcohol intake. Metabolic acidosis with a normal anion gap (10 meq/L) was observed together with moderate hyperglycemia and a 2 + (but not 4 +) test for serum ketones. None of the usual causes of metabolic acidosis with a normal anion gap was identified nor was there an obvious explanation for a reduction in unmeasured anion gap (e.g., hypoalbuminemia, dysproteinemia, or the presence of abnormal halides). Despite the initial normal anion gap, ketoacidosis was suspected clinically and this was confirmed by the elevated serum B-hydroxybutyrate of 8 mmol/L. We deduced that the serum unmeasured anions, which should have been increased by at least 8 meq/L, were being underestimated because of the effect of hypertriglyceridemia on the serum chloride determination. When the serum chloride was reestimated by a method not influenced by hyperlipidemia, the value was 102 mmol/L not 112 mmol/L and, when reevaluated, the anion gap was indeed appropriately elevated. In addition, the urine anion gap (Na + K - Cl) was 103 meq/L in the absence of renal disease. This indicated that the expected large quantity of urinary ammonium must have been masked by an even greater quantity of unmeasured anion; in this case proven by direct measurement to be B-hydroxybutyrate. Finally, metabolism of the alcohol ingested, which yields hepatic NADH, could explain, in part, the modest hyperglycemia and the absence of a 4 + test for serum ketones.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Total parenteral nutrition with hypertonic glucose/AA solutions given to eighteen nutritionally depleted patients resulted in a rise in the respiratory quotient (RQ) from 0.83 to 1.05 (p less than .001), while oxygen consumption (VO2) increased only 3%. Excess glucose in depleted patients was converted to fat as evidenced by an RQ greater than 1.0. Administration of a similar glucose load to fourteen hypermetabolic patients (injury/infection) resulted in a rise in RQ from 0.76 to 0.90 while VO2 increased 29% (p less than .001) In hypermetabolic patients, even with administration of glucose in quantities above energy expenditure, there was still ongoing utilization of fat for energy, resulting in a RQ significantly less than 1.0. Excess glucose under these circumstances is apparently converted to glycogen while fat stores are utilized to partially meet energy needs. Septic and injuried man seems to preferentially utilize endogenous fat as an energy source. Administration of a large glucose load to hypermetabolic patients does not totally suppress the net fat oxidation as it does in depleted patients. Rather there is an increase in VO2, continuing oxidation of fat and apparently an increase in the conversion of glucose to glycogen.
Article
A 19-yr-old woman developed ketoacidosis 7 wk after the delivery of her first child. Despite breast feeding, she had been on a weight reduction diet resulting in a loss of 12 kg/body wt. With the development of a urinary tract infection, the patient became dehydrated and was found to be in ketoacidosis (arterial pH was 7.25 and PaCO2 was 17 mm Hg). The patient did not use alcohol and was nondiabetic. Therapy with adequate calories, intravenous fluids, and an appropriate antimicrobial agent resulted in prompt normalization of the laboratory abnormalities and resolution of the patient's symptoms. The hypothesis is advanced that the postpartum status of the patient put her at particular risk for development of ketoacidosis and that this may represent the first reported episode of "bovine ketosis" in a human.
Article
Ischemic brain injury is the third-leading cause of death among Americans and the leading cause of serious disability. Based on studies of animal models, a substantial amount of experimental evidence shows that hyperglycemia at the onset of brain ischemia worsens postischemic neurologic outcome. Consistent with these observations, hyperglycemia also is associated with a worsening of postischemic brain injury in humans. In humans, however, data are often difficult to interpret because of problems in determining the timing of hyperglycemia relative to a critical ischemic event and in elucidating the effect of coexisting pathophysiologic processes (for example, a stress response) on outcome. Glucose modulation of neurologic injury is observed when ischemia is either global (for example, that accompanying cardiac arrest or severe systemic hypotension) or focal (for example, that accompanying thrombotic or embolic stroke). Toxicity is probably the result of an intracellular lactic acidosis. Specifically, the associated hydrogen ions are injurious to neurons and glia. On the basis of these factors, we recommend diligent monitoring of blood glucose concentrations in patients who are at increased risk for new-onset, ongoing, or recurring cerebral ischemia. In such patients, the use of fluid infusions, corticosteroid drugs, and insulin, as well as stress management, should be tailored to treat preexisting hyperglycemia and prevent new-onset hyperglycemia. Maintenance of normoglycemia is recommended. When one attempts to treat preexisting hyperglycemia, care should be taken to avoid rapid fluid shifts, electrolyte abnormalities, and hypoglycemia, all of which can be detrimental to the brain.
Article
Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies.
Article
The widespread use of ion-selective electrode causes the reference range of the anion gap (AG) to be lowered from 8-16 to 3-11 mmol/l. The use of the outdated reference range (8-16 mmol/l) leads to the misinterpretation of the value of the anion gap. To interpret the anion gap accurately, one must use an analyzer-specific reference range. This study established the reference ranges of the electrolyte and anion gap in four ion-selective electrode analyzers. We collected clotted and lithium-heparinized blood from 124 healthy volunteers. We determined the electrolyte in the Beckman E4A (serum), Beckman Synchron CX5 (serum), and Nova CRT (serum and plasma). The anion gap was calculated from the formula: [Na(+)-(Cl(-)+HCO3(-))]. Blood sodium, potassium and bicarbonate were determined using the Nova Stat Profile Ultra. We used the plasma chloride from the Nova CRT to calculate the value of the anion gap in the Nova Stat Profile Ultra. We established the reference ranges using the non-parametric percentile estimation method. Accuracy and precision of the electrolyte performances obtained from all analyzers were acceptable. Reference values of serum and plasma sodium, potassium, and chloride were similar in all analyzers. The value of blood sodium obtained from the Nova Stat Profile Ultra was slightly higher than the values for the serum and plasma sodium obtained from the other analyzers. The bicarbonate ranges obtained from the Nova analyzers were higher than the values obtained from the Beckman analyzers. For the anion gap, the reference ranges in this study were low but similar to other studies (3-11 mmol/l) using ion-selective electrode. However, our reference ranges were lower than the previous reference ranges obtained from the continuous-flow analyzer (8-16 or 9-18 mmol/l) incorporated with flame photometry and colorimetry techniques.
Article
Objective: Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. Patients: Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. Interventions: We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate < 22 mmol/l) either with or without increased UMA (> 3 mEq/l). Measurements and results: Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P < 0.0001) but not a lower absolute Cl (P = 0.5) in the acidotic subgroup with raised UMA, and by the inverse relationship between TA and the Cl:Na ratio. (coefficient of determination (r2) = 0.37, P < 0.0001). The best discriminator for the presence of raised TA was the albumin-corrected anion gap (AGcorr), however, this could not track changes in TA with clinical accuracy. The Cl:Na ratio discriminated reasonably well, a ratio of < 0.75 identified TA (positive predictive value (PPV) 88%) with a likelihood ratio (LR) similar to the AG (7.8 vs7.4). Conversely, a high ratio (> 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. Conclusion: In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.
Reference ranges of electrolyte and anion gap on the Beckman E4A
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Lolekha PH, Vanavanan S, Teerakarnjana N, Chai-chanajarernkul U: Reference ranges of electrolyte and anion gap on the Beckman E4A, Beckman Synchron CX5, Nova CRT, and Nova Stat Profile Ultra. Clin Chim Acta 307:87-93, 2001 SEVERE ACIDOSIS CAUSED BY STARVATION AND STRESS
Bo-vine ketosis " in a nondiabetic postpartum woman Lewis P: Starvation ketosis after rehydration with diet soda
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Chernow B, Finton C, Rainey TG, O'Brian JT: " Bo-vine ketosis " in a nondiabetic postpartum woman. Diabetes Care 5:47-49, 1982 21. Lewis P: Starvation ketosis after rehydration with diet soda. Pediatrics 88:806-807, 1991
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