Severe Metabolic Derangements Research Articles

Concurrent acute spontaneous tumor lysis syndrome complicated with multiple organ failure in a patient with pre-existing undiagnosed lung cancer.

Acute kidney injury, a common complication associated with malignancy, occurs in various clinical situations for numerous reasons. Acute tumor lysis syndrome (TLS) is possibly the most significant cause of acute kidney injury in cancer patients, because it is fulminant at onset and associated with severe metabolic derangements. Acute spontaneous tumor lysis syndrome is rare and most of the related malignancies belong to hematologic malignancies but it has seldom been investigated as bulky or advanced metastatic non-hematologic malignancies. TLS comprises a clinical laboratory derangement of cellular metabolism which can lead to acute renal impairments, cardiac arrhythmia, seizures and patient demise. Prevention and treatment of tumor lysis syndrome depends on early recognition of at-risk patients, volume repletion and xanthin oxidase inhibitors. In addition, in patients with high risk tumor types, prophylactic use of rasburicase before chemotherapy is required. If dialysis is required, continuous modalities may be favored, particularly in patients with more severe TLS. This case report discusses a 79-year-old man with controlled Alzheimer's disease presented with picture of septic shock and multiorgan dysfunction (acute kidney injury, acute lung injury, acute brain injury) pulmonary suppuration in the right lung field due to aspiration pneumonia with infection-induced systemic inflammatory response (SIRS) was diagnosed. Further work-up revealed lung cancer on chest CT scan. Antibiotic, respirator and hemodialysis treatment improved his condition but died several days later. Acute spontaneous TLS may present in association with infectious SIRS and multiple organ failure, the combination of which results in significant mortality.

G203(P) Status dystonicus presenting in an acute setting in association with viral illnesses

<h3>Aims</h3> We report 2 cases of status dystonicus seen in our hospital in 2014. Status dystonicus is a rare condition with a potentially life-threatening outcome. The patients’ background, clinical features, management, likely triggers, differential diagnosis and outcome is discussed. <h3>Methods</h3> Review of charts. Review of existing literature. <h3>Description</h3> <i>Case1</i>:A 9-year-old female with dystonic quadriparesis GMFCS class IV, intellectual disability and gastrostomy feeds was admitted with a febrile illness (pneumonia) and treated with intravenous antibiotics, oxygen and fluid support. Her dystonic movements had not required treatment before this. During the admission, she developed severe abnormal movements and unusual posturing with sustained hyperpyrexia, sweating and rising creatinine kinase (CK) &gt; 23,000. Blood and urine cultures were negative. She was intubated and ventilated, transferred to PICU, and received chloral hydrate, clonidine, and oseltamivir. She was subsequently confirmed as having Influenza A, H3N2 strain. During recovery, sedation was gradually weaned; however, dystonic movements recurred, requiring institution of a slower weaning regimen. She went home on trihexyphenidyl and remains well. <i>Case2</i>: A 5-year-old male with microcephaly, spastic quadriparesis GMFCS class V (intra-thecal baclofen pump), visual impairment, profound intellectual disability, recurrent urinary tract infections (UTI), nephcalcinosis, gastrostomy feeds was admitted with Pseudomonas UTI and treated with ciprofloxacin. His recovery was complicated by norovirus gastro-enteritis with dehydration, pre-renal failure and increasingly severe dystonic posturing (tongue protrusion, sustained muscle contractions, ophisthotonus) with fever, sweating and rising CK (&gt; 23000). He was treated with: transfer to HDU, close management of fluid and electrolyte balance, sedation with chloral hydrate, clonidine and midazolam. Resolution of the movement disorder and fever and normalisation of CK followed. He re-presented a month later with similar symptomatology; however, early treatment with hydration, clonidine and chloral hydrate appeared to halt progression to status dystonicus. He went home on low-dose clonidine and remains well. <h3>Conclusion</h3> Status dystonicus is a rare condition with a high morbidity and mortality. A rising CK, severe dystonic movements and metabolic derangements suggest the diagnosis. Maintaining a high index of suspicion can identify such cases early and halt further progression. CK is simple test to monitor response to treatment.

Partial and Generalized Lipodystrophy: Comparison of Baseline Characteristics and Response to Metreleptin

Lipodystrophies are extreme forms of metabolic syndrome. Metreleptin was approved in the United States for generalized lipodystrophy (GLD) but not partial lipodystrophy (PLD). The objective of the study was to test metreleptin's efficacy in PLD vs GLD and find predictors for treatment response. This was a prospective, single-arm, open-label study since 2000 with continuous enrollment. Current analysis included metreleptin treatment for 6 months or longer as of January 2014. The study was conducted at the National Institutes of Health (Bethesda, Maryland). Patients clinically diagnosed with lipodystrophy, leptin less than 8 ng/mL (males) or less than 12 (females), age older than 6 months, and one or more metabolic abnormalities (diabetes, insulin resistance, or hypertriglyceridemia) participated in the study. The interventions included sc metreleptin injections (0.06-0.24 mg/kg · d). Changes in glycated hemoglobin A1c (HbA1c) and triglycerides after 6 and 12 months of metreleptin were measured. Baseline metabolic parameters were similar in 55 GLD [HbA1c 8.4% ± 2.3%; triglycerides, geometric mean (25th, 75th percentile), 467 mg/dL (200, 847)] and 31 PLD patients [HbA1c 8.1% ± 2.2%, triglycerides 483 mg/dL (232, 856)] despite different body fat and endogenous leptin. At 12 months, metreleptin decreased HbA1c (to 6.4% ± 1.5%, GLD, P < .001; 7.3% ± 1.6%, PLD, P = .004) and triglycerides [to 180 mg/dL (106, 312), GLD, P < .001; 326 mg/dL (175, 478), PLD, P = .02]. HbA1c and triglyceride changes over time significantly differed between GLD and PLD. In subgroup analyses, metreleptin improved HbA1c and triglycerides in all GLD subgroups except those with baseline triglycerides less than 300 mg/dL and all PLD subgroups except baseline triglycerides less than 500 mg/dL, HbA1c less than 8%, or endogenous leptin greater than 4 ng/mL. In addition to its proven efficacy in GLD, metreleptin is effective in selected PLD patients with severe metabolic derangements or low leptin.

A Natural Course of an Infantile Hypertrophic Pyloric Stenosis without Adequate Surgical Procedure

Infantile hypertrophic pyloric stenosis (IHPS) is one of the common surgical abdomen in infancy, characterized by progressive non-bilious vomiting. The etiology is unknown, but it likely develops after birth. The pylorus of the stomach becomes thick and triggers progressive vomiting. Abdominal ultrasonography (US) is widely used as a diagnostic tool. Currently, there is a rare IHPS patient with severe metabolic derangement because of general use of abdominal US and its accuracy. We experienced a natural course of a 62- day-old male infant with IHPS who was suffering from intermittent vomiting, loss of weight but had not been properly treated for 1 month. It is needed to make an effort to diagnose differentially in recurrent vomiting infant and check-up regularly, and also educate parents properly.

Anesthetic Management of Emergent Laparoscopic Bilateral Adrenalectomy in a Patient with a Life-Threatening Cortisol Crisis

Cushing syndrome may rarely present with life-threatening hypercortisolism, manifested by hypertension, hypokalemia, hyperglycemia, and edema. If medical treatment proves ineffective in ameliorating the symptoms, emergent rescue adrenalectomy may be the only way to relieve the crisis. We describe the anesthetic management of a patient with an ectopic adrenocorticotropic hormone-secreting tumor, whose condition was rapidly deteriorating due to severe cortisol excess, and emergent adrenalectomy was the only available therapeutic modality. Despite severe metabolic derangement, edema, and incipient respiratory failure, emergent bilateral laparoscopic adrenalectomy was performed and the patient improved sufficiently to undergo surgery for the ectopic lesion without incident.

Prevalence and spectrum of illness among hospitalized adults with malaria in Blantyre, Malawi.

BackgroundAs control interventions are rolled out, the burden of malaria may shift from young children to older children and adults as acquisition of immunity is slowed and persistence of immunity is short-lived. Data for malaria disease in adults are difficult to obtain because of co-morbid conditions and because parasitaemia may be asymptomatic. Regular surveys of adult admissions to a hospital in Malawi were conducted to characterize the clinical spectrum of malaria and to establish a baseline to monitor changes that occur in future.MethodsIn 2011–2012, at Queen Elizabeth Hospital, Blantyre, four separated one-week surveys in the peak malaria transmission period (wet season) and three one-week surveys in the low transmission period (dry season) were conducted using rapid diagnostic tests (RDT) with confirmation of parasitaemia by microscopy. All adults (aged ≥15) being admitted to the adult medical wards regardless of the suspected diagnosis, were enrolled. Participants with a positive malaria test underwent a standardized physical examination and laboratory tests. Malaria syndromes were characterized by reviewing charts and laboratory results on discharge.Results765 adult admissions were screened. 63 (8.2%) were RDT-positive with 61 (8.0%) positive by microscopy. Over the course of the seven study weeks, two patients were judged to have incidental parasitaemia, 31 (4.1%) had uncomplicated malaria and 28 (3.7%) had severe malaria. Both uncomplicated and severe malaria cases were more common in the rainy season than the dry season. Prostration (22/28 cases) and hyperparasitaemia (>250,000 parasites/μl) (9/28) were the most common features of severe malaria. Jaundice (4/28), severe anaemia (2/28), hyperlactataemia (2/28), shock (1/28) and haemoglobinuria (1/28) were less commonly seen, and no patient had severe metabolic derangement or organ failure. There were no deaths attributable to malaria.ConclusionIn this study of adults admitted to hospital in southern Malawi, an area with year-round transmission of Plasmodium falciparum, classical metabolic and organ complications of malaria were not encountered. Prostration and hyperparasitaemia were more common indicators of severity in patients admitted with malaria, none of whom died. These data will provide a baseline for monitoring trends in the frequency and clinical patterns of severe malaria in adults.

The Effect of a Diiodothyronine Mimetic on Insulin Sensitivity in Male Cardiometabolic Patients: A Double-Blind Randomized Controlled Trial

Background and aimsObesity and its associated cardiometabolic co-morbidities are increasing worldwide. Since thyroid hormone mimetics are capable of uncoupling the beneficial metabolic effects of thyroid hormones from their deleterious effects on heart, bone and muscle, this class of drug is considered as adjacent therapeutics to weight-lowering strategies. This study investigated the safety and efficacy of TRC150094, a thyroid hormone mimetic.Materials and MethodsThis 4-week, randomized, placebo-controlled, double-blind trial was conducted in India and The Netherlands. Forty subjects were randomized at a 1∶1 ratio to receive either TRC150094 dosed at 50 mg or placebo once daily for 4 weeks. Hyperinsulinemic euglycemic clamp and 1H-Magnetic Resonance Spectroscopy (MRS) were performed before and after treatment.ResultsAt baseline, subjects were characterized by markedly impaired hepatic and peripheral insulin sensitivity. TRC150094 dosed 50 mg once daily was safe and well tolerated. Hepatic nor peripheral insulin sensitivity improved after TRC150094 treatment, expressed as the suppression of Endogenous Glucose Production from 59.5 to 62.1%; p = 0.477, and the rate of glucose disappearance from 28.8 to 26.4 µmol kg−1min−1, p = 0.185. TRC150094 administration did not result in differences in fasting plasma free fatty acids from 0.51 to 0.51 mmol/L, p = 0.887 or in insulin-mediated suppression of lipolysis from 57 to 54%, p = 0.102. Also, intrahepatic triglyceride content was unaltered.ConclusionCollectively, these data show that, in contrast to the potent metabolic effects in experimental models, TRC150094 at a dose of 50 mg daily does not improve the metabolic homeostasis in subjects at an increased cardiometabolic risk. Further studies are needed to evaluate whether TRC150094 has beneficial effects in patients with more severe metabolic derangement, such as overt diabetes mellitus and hypertriglyceridemia.Trial Registrationclinicaltrials.gov NCT01408667

Compartment Syndrome and Rhabdomyolysis Presenting with the Rare Pseudo-Infarction Pattern of Hyperkalemia

The rapid identification and treatment of patients with ST-segment elevation myocardial infarction (STEMI) is a priority for emergency department providers. Occasionally conditions other than acute coronary syndrome (ACS) can mimic the presence of ST-elevation on electrocardiogram (ECG), making the accurate identification of these patients challenging. We present a case in which severe metabolic derangements resulted in a rare pseudo-STEMI pattern on ECG. A 26 year old male was found at home by family after a reported fall. A pre-hospital ECG conducted by EMS personnel indicated STEMI and the cardiac catheterization team was activated prior to patient arrival. Before undergoing PCI, laboratory values revealed severe hyperkalemia and rhabdomyolysis. Treatment of the patient’s hyperkalemia resulted in resolution of ECG abnormalities. The patient later developed acute compartment syndrome and underwent emergent fasciotomy. This case demonstrates the rare pseudo-infarction pattern of hyperkalemia and underscores the importance of clinical context in the initial evaluation of the emergency patient.

Fulminant Hepatitis: Definitions, Causes and Management

Fulminant hepatitis (FH) is a rare and devastating syndrome caused by a variety of hepatic insults. It characterized by severe metabolic derangements, neurologic complications and ultimately, multiorgan failure. Liver transplantation is the gold standard therapy for patients with irreversible FH. The major areas of current research in this field include the development of: hepatic support devices, strategies to accelerate hepatic regeneration and criteria for accurate prognostic classification of patients. This review aims to focus on the definitions, aetiologies and management strategies for FH.

Management of acute hyperglycemic emergencies: focus on diabetic ketoacidosis.

Management of acute hyperglycemic emergencies: focus on diabetic ketoacidosis.

The Blue Man

Muriatic acid (hydrochloric acid), a common cleaning and resurfacing agent for concrete pools, can cause significant burn injuries. When coating a pool with chlorinated rubber-based paint, the pool surface is initially cleansed using 31.45% muriatic acid. Here we report a 50-year-old Hispanic male pool worker who, during the process of a pool resurfacing, experienced significant contact exposure to a combination of muriatic acid and blue chlorinated rubber-based paint. Confounding the clinical situation was the inability to efficiently remove the chemical secondary to the rubber-based nature of the paint. Additionally, vigorous attempts were made to remove the rubber paint using a variety of agents, including bacitracin, chlorhexidine soap, GOOP adhesive, and Johnson's baby oil. Resultant injuries were devastating fourth-degree burns requiring an immediate operative excision and amputation. Despite aggressive operative intervention and resuscitation, he continued to have severe metabolic derangements and ultimately succumbed to his injuries. We present our attempts at debridement and the system in place to manage patients with complex chemical burns.

Physical Parameters and Risk Factors Associated with the Elimination of Arabian and Crossed Arabian Endurance Horses during a 120-km Endurance Race

Endurance racing is one long-distance event among the equine sporting activities associated with severe injuries and metabolic derangements that impede the health status of horses participating in the event. Therefore, this study evaluated the physical parameters and risk factors associated with the elimination of Arabian and crossed Arabian endurance horses during a 120-km race. Fifty-three Arabian and crossed Arabian endurance horses aged 6 to 15 years old participated in an endurance race of 120 km. All the horses were examined and found fit according to Fédération Équestre Internationale (FEI) regulations. After the endurance race 14 Arabian endurance horses completed the race successfully while 31 Arabian and crossed Arabian were eliminated. Their speed and heart rates were significantly higher (P < .0001). There were significant differences in skin recoil (P < .0395), color of mucous membrane (P < .0189), intestinal motility (P < .0124), and capillary refill time (P < .0082). There also were significant differences in age (P < .0018), breed (P < .0119), and equine establishments (P < .0205) among the eliminated horses and the Arabian and crossed Arabian endurance horses that successfully completed the race. In conclusion, the physical parameters and risk factors were significantly associated with the elimination of Arabian and crossed Arabian endurance horses. Therefore, close monitoring of the physical parameters and risk factors are essential in order to improve the performance of Arabian and crossed Arabian horses, and further studies are required on other associated parameters.

Glycemic control in familial vs. sporadic type 1 diabetes patients over 5 years

Studies have shown that familial type 1 diabetes patients (FTID) have less severe metabolic derangement at presentation compared to sporadic patients (ST1D), but data on long-term metabolic control are lacking. (1) FT1D will have less severe presentation and better HbA1c over 5 years compared to ST1D; (2) HbA1c in the offspring will correlate with parent HbA1c in parent-offspring group; and (3) HbA1c of the second affected sibling (SP2) will correlate with the first affected sibling (SP1) in sib-pairs. Cohort of 33 parent-offspring and 19 sib-pairs; controls included 33 sporadic subjects matched by age, sex, ethnicity, puberty, and insulin regimen. Paired t-test and Pearson's correlation were used for statistical analysis. At diagnosis, mean age in FT1D vs. matched ST1D (7.7±4.9 vs. 7.6±4.5 years), mean HbA1c (9.6% vs. 10.7%), HCO3 (21 vs. 18 meq/L), glucose (428 vs. 463 mg/dL) and pH (7.35 vs. 7.36; p=ns) were not different. At 5 years, HbA1c (8.9% vs. 8.8%; p=0.81), clinic visits (12 vs. 12.5, p=0.68) and emergency room visits (0.48 vs. 0.24, p=0.10) were not different. In affected siblings, only HCO3 was different (SP1:18 vs. SP2: 24 meq/L; p<0.01). HbA1c for SP2 correlated positively with SP1 (r=0.67, p<0.01). Offspring HbA1c correlated positively with affected parents (9.3% vs. 8.6%, r=0.57, p=0.18) but was not significant. Metabolic control at diagnosis and at 5 years was similar in FT1D and ST1D. In sib-pairs, the second affected sibling had milder clinical presentation compared to the first affected sibling.

Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

Cancer-related anorexia and cachexia syndrome (CACS) is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or stages, moving from precachexia through overt cachexia to advanced or refractory cachexia. The purpose of this review is to describe currently effective approaches for the treatment of cachexia, moving forward to drugs and treatments already shown to be effective but needing further clinical trials to confirm their efficacy. We then introduce novel promising investigational drugs and approaches which, based on a strong rationale from the most recent data on the molecular targets/pathways driving the pathophysiology of cachexia, need to be tested either in currently ongoing or appropriate future clinical trials to confirm their clinical potential. Although different drugs and treatments have been tested, we can speculate that a single therapy may not be completely successful. Indeed, considering the complex clinical picture and the multifactorial pathogenesis of CACS, we believe that its clinical management requires a multidisciplinary and multitargeted approach. In our opinion, appropriate treatment for cachexia should target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, immunosuppression, quality of life, and above all, fatigue. A comprehensive list of the most interesting and effective multitargeted treatments is reported and discussed, with the aim of suggesting the most promising with regard to clinical outcome. A critical issue is that of testing therapies at the earliest stages of cachexia, possibly at the precachexia stage, with the aim of preventing or delaying the development of overt cachexia and thereby obtaining the best possible clinical outcome for patients.

Baking Soda Pica Associated With Rhabdomyolysis and Cardiomyopathy in Pregnancy

Pica is a commonly underappreciated disorder in pregnancy that can lead to several complications, including severe metabolic derangements and other adverse outcomes. We report a case of baking soda pica in pregnancy associated with both rhabdomyolysis and cardiomyopathy. A multigravid woman at 37 weeks of gestation presented with weakness and severe hypokalemia. She subsequently had development of rhabdomyolysis and presumed peripartum cardiomyopathy. After delivery, it was discovered that the patient had a long history of consumption of large quantities of baking soda. Her condition improved with cessation of the pica. Clinicians must have a high index of suspicion for pica in pregnancy because it can lead to complex diagnostic challenges and pregnancy complications. The diagnosis should be considered in a patient with unexplained metabolic abnormalities.

Cardiogenic Shock and the ICU Patient

Cardiogenic shock is one of the most important complications of acute myocardial infarction (MI) and acute left ventricular failure (LVF). It threatens the life of 5–10% of patients with ST-segment elevation myocardial infarction (STEMI) particularly in the presence of inappropriately low peripheral vascular resistance. Cardiogenic shock results in poor tissue perfusion, end-organ damage and carries a high mortality risk. The goal of therapy is to prevent end-organ dysfunction and severe metabolic derangement by raising mean arterial blood pressure, which is achieved with the use of inotropes and vasopressors, often at the expense of tachycardia, elevated myocardial oxygen consumption and extended myocardial ischaemia. Current therapeutic approaches include early coronary artery revascularisation (which has significantly improved the survival rate), fluid resuscitation, inotropic support and mechanical circulatory support using intra-aortic balloon pumps or ventricular assist devices. In this article, we review the pathophysiology, diagnosis and management of cardiogenic shock.

Insulin therapy in sepsis

Severe metabolic derangement is characteristic of systemic inflammatory response in septic conditions. Changes in blood glucose levels are often deleterious further impairing organ functioning. Thus they are a subject of strict and sometimes even too aggressive control. Its disadvantages demand and stimulate research of new strategies. In the present paper we systematically review the current therapeutic options and recent research advances in the field of hyperglycemia in sepsis. They include the pathogenesis of sepsis and the role of insulin in this pathology. A special attention is paid to the glycemic control in sepsis. The correct strategy of glycemic control is combined approach with computerized infusion, continuous blood glucose monitoring and proper feeding support. Scripta Scientifica Medica 2013; 45(1): 7-11.

Acute Thrombosis of the Abdominal Aorta Secondary to Low Cardiac Output Syndrome

Acute aortic occlusion is a rare but catastrophic pathology with very high morbidity and mortality. It may result from thrombus formation, saddle embolism and other etiologies related to arteriosclerosis, low flow states or hypercoagulability. The clinical presentations include ischemic and neurologic symptoms of the lower extremities, abdominal symptoms and acute hypertension. We present a case of acute aortic occlusion resulting from in situ thrombosis secondary to a low cardiac output state due to MI. A 61-year-old man underwent sigmoid colon resection for volvulus formation 5 days before his acute presentation. He presented as acute inferior MI with low cardiac output syndrome. Successful stent implantation of the RCA was performed as an emergency via the right brachial artery since the femoral pulses were not palpable. Abdominal aortography showed total occlusion of the abdominal aorta distal to the renal arteries. Emergency bilateral femoral embolectomy was performed with local anesthesia, resulting in good distal pulses. Postoperatively, he deteriorated with acidosis, hypotension, oliguria and increased inotrop requirement. He died of cardiac failure and severe metabolic derangement on the second day after operation. Early diagmosis and treatment is very important for preventing metabolic compromise in these patients. The choice of surgical procedure depends on the general condition of the patient, the presence of chronic aortic occlusive disease, presence of renal and mesenteric ischemia and cardiac function of the patient. (JAREM 2012; 2: 124-6)

Nursing care of the burns patient

Nursing patients with burn injuries can be hugely challenging as the individual may have severe metabolic, cardiovascular and pulmonary derangements, not to mention large tissue deficits. A range of systems have been developed to classify burn wounds including percentage of body surface involved, through to depth of tissue involved and the use of these systems may help in giving a prognosis of the extent of the injury. The treatment of burn wounds can start at home by the owner and appropriate early therapy can make a huge difference to the extent of the injury. All major body systems may be affected due to the nature of the injury and so early fluid therapy, analgesia, respiratory derangements, including carbon monoxide toxicity, wound management and analgesia need to be addressed appropriately. The close monitoring of these patients is vital in order to achieve a good outcome and so these cases rely heavily on good nursing care and attention to detail, so a good background knowledge of these considerations is essential.

“Brittleness” in Diabetes: Easier Spoken than Broken

By definition, brittle diabetes (BD) is an unstable condition. Patients with BD suffer chronically from poor metabolic control, characterized by severe instability of glycemic values with frequent and unpredictable hypoglycemic and/or diabetic ketoacidosis episodes that cannot be attributed to failure in management. Quality of life is dramatically compromised because of very frequent acute complications leading to hospital admissions and because of premature chronic complications. It remains difficult to identify all patients with BD as diagnostic criteria are still not well defined. In practice, metabolic instability is manifested most obviously by chaotic glycemic profiles, which show greater and more unpredictable variation than in "stable" patients with diabetes. It is important that patients with BD are not adequately controlled, even by closely supervised, intensive insulin regimens, including continuous subcutaneous and/or intravenous insulin infusion. Their care is often very expensive in terms of time and resources, and their lives are constantly at risk for severe metabolic derangement. Management can also be frustrating and demoralizing for everyone involved, including the patient's family as well as the diabetes care team. Adopting a team approach, involving a broad range of disciplines, is essential in treating patients with BD and helping them to achieve and maintain both normoglycemia and quality of life.