Diabetic Ketoasidosis (DKA) is metabolic disturbance disorder that be signed by Bagian/SMF Ilmu Penyakit Dalam, FK Unud/RSUP Sanglah Denpasar. PDF. Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) appear as 2 extremes in the spectrum of diabetic decompensation.1 They. These documents are available to download from the ABCD website at http:// terney.info Diabetic ketoacidosis (DKA) , though preventable, remains a frequent and life threatening complication of.
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Diabetic. Ketoacidosis. DKA. Resource Folder. by Eva Elisabeth Oakes, RN, nurses who have not cared for a patient with diabetic ketoacidosis for some Available URL: terney.info < Accessed . PDF | Diabetes mellitus (DM), belongs to the class of metabolic diseases which the main symptom associated with this Download full-text PDF . threatening to the life is the hyperglycemia accompanied with ketoacidosis or. PDF | Introduction: Diabetic ketoacidosis (DKA) is an acute complication of diabetes mellitus that requires prompt treatment. However Download full-text PDF.
T1DM is caused by destruction of pancreatic beta cells by autoreactive T-cells. Non-obese diabetic NOD mice have been studied extensively as an experimental model since they feature many aspects of T1DM similar to humans. Nivolumab was approved by the FDA in for the second line treatment of advanced NSCLC based on the results of two large randomized open-label phase III trials which demonstrated a survival benefit for patients treated with nivolumab versus docetaxel [ 14 , 15 ].
The first of these to be published Checkmate included patients with squamous cell lung carcinoma randomized to treatment with nivolumab or docetaxel. A subsequently published trial Checkmate included patients with advanced NSCLC randomized to treatment with nivolumab or docetaxel.
No episodes of treated-related hyperglycemia or DKA were noted in either of these studies. Blood glucose levels were normal prior to the initiation the treatment with nivolumab.
At the time of diagnosis of autoimmune diabetes, the HbA1C value was 7. The presence of GAD 65, IA-2, and ZnT8 antibodies prior to treatment may have predisposed the patient to the development of autoimmune diabetes. After treatment nivolumab and at onset of diabetes after treatment with exogenous insulin , IAA seroconverted from negative to positive, perhaps demonstrating the enhanced immune activation against islet antigens.
In contrast to other autoimmune sequelae of anti-PD1 therapy such as pneumonitis or colitis that are routinely treated with high dose steroids per clinical trial protocol specifications and published guidelines, there is little data regarding the use of steroids in the setting of autoimmune diabetes.
High dose steroids are usually avoided since they exacerbate hyperglycemia and complicate the management of insulin dependent diabetes.
Standard irAE immunosuppression with prednisolone in an attempt to reverse pembrolizumab-induced T1DM did not salvage beta cell function in one case reported by Aleksova et al. Current management includes traditional treatment strategies for DKA, including intravenous IV insulin therapy, IV hydration and frequent monitoring of labs to correct the anion gap and electrolyte derangements.
Co-management and communication between medical oncology and endocrinology is essential to coordinate education and close outpatient follow-up to optimize patient outcomes. Development of DKA is not an absolute contraindication to continuing nivolumab therapy in patients with advanced NSCLC once the DM is well-controlled, given the paucity of treatment options for these patients.
In keeping with a shared decision making model, careful discussion of risks and benefits between the patient and clinician is required. Of note, our patient has experienced a significant ongoing response to nivolumab and has not received antineoplastic treatment since December Since it is not standard practice to check for the presence of diabetes autoantibodies prior to ICI treatment, the pre-treatment diabetes antibody status was typically unavailable for the previously reported cases.
However, Lowe et al reported a case of autoimmune diabetes following combination therapy with ipilimumab and nivolumab that demonstrated anti-GAD antibody seroconversion from negative to positive [ 6 ].
It is not known whether diabetes antibodies were present prior to ICI treatment in the other reported cases to date. To our knowledge, this is the first reported case to describe a patient who was found to have GAD 65, IA-2 and ZnT8 antibodies prior to treatment with nivolumab who then subsequently developed new insulin antibodies and autoimmune diabetes following treatment. PD-1 inhibition may have simply accelerated a pre-existing autoimmune process that ultimately led to the development of T1DM in this patient.
Although our patient did not have any first degree relatives with diabetes, she almost certainly was at increased risk of developing T1DM prior to treatment with nivolumab due to the presence of these antibodies. Reported cases of T1DM related to anti PD-1 have shown conflicting results regarding the presence of diabetes related autoantibodies after development of T1DM.
Hughes et al.
Three of the five patients described developed at least one positive diabetes related autoantibody after onset of T1DM [ 5 ]. At least half of the reported cases of ICI related autoimmune diabetes show no detectable diabetes autoantibodies at onset [ 2 , 4 , 5 , 8 , 9 , 10 ].
Similar results have been found in the NOD mouse model of autoimmune diabetes. Ansari and colleagues found no correlation between insulin autoantibody levels and development of autoimmune diabetes in NOD mice treated with PD-1—PD-L1 blockade; some mice developed diabetes with no antibodies and others developed antibodies but did not develop diabetes [ 13 ].
As the approved indications for anti-PD1 therapy expand in the coming years, the number of patients receiving these drugs will dramatically increase, as will the frequency of autoimmune adverse events. Medical oncologists must be aware of the possibility of anti-PD1 therapy induced autoimmune diabetes and counsel their patients to report symptoms that may be related to DKA, as this is a medical emergency.
The presence of diabetes autoantibodies prior to anti-PD1 therapy likely predisposed our patient to developing T1DM. Future correlative studies in this small patient population are needed to delineate genetic and immunologic biomarkers to identify those at highest risk for autoimmune sequelae, such as autoimmune DM.
These studies did not report any fatal outcomes secondary to hypokalemia; however, the theoretical risk is of substantial concern, especially when considering the widespread use of this intervention.
Acute reversal of acidosis with bicarbonate has previously been linked to worsening tissue oxygenation. Acidosis will induce the Bohr effect and reduce total hemoglobin-oxygen affinity. However, it also lowers the concentration of 2,3-DPG in erythrocytes which leads to a counter-active increased hemoglobin-oxygen affinity.
There exists a delicate balance in favor of the Bohr effect in the initial presentation of DKA, which theoretically can be pushed towards lower 2,3-DPG levels with bicarbonate administration and abrupt acidemia reversal. However, there is evidence to suggest that this may occur regardless of bicarbonate administration, and levels of 2,3-DPG remain quite low for several days beyond the treatment of acidosis[ 19 ].
Finally, bicarbonate administration can lead to post-treatment metabolic alkalosis as insulin mediated ketoacid metabolism leads to both spontaneous bicarbonate generation and resolution of metabolic acidosis.
Although no prospective randomized trials have been conducted on patients with severe DKA, the American Diabetes Association recommends the administration of mmol sodium bicarbonate in mL sterile water with 20 mEq of KCl to patients with a pH of less than 6.
This is largely due to the concern of cardiovascular compromise in the setting of severe acidemia[ 8 ]. Additionally, bicarbonate administration is reasonable in the setting of life threatening hyperkalemia, since its administration may shift potassium into cells. Another potential setting in which bicarbonate therapy may be helpful is during the recovery phase.
Intravenous hydration therapy with 0. Also contributing to hyperchloremia is the preferential renal excretion of ketones over chloride anions. This may lead to reduced renal bicarbonate genesis in the setting of concomitant kidney injury and volume related hyperchloremic acidosis. This is perhaps the mechanism of the initial favorable physiologic outcome in the two previously discussed RCTs[ 14 , 16 ] with bicarbonate therapy as it may represent a reduced risk of hyperchloremic acidosis.
However, the evidence is weak at best: the effect was transient and of uncertain clinical significance. Taken in context of patient care, the theoretical benefits that provided the rational basis of rapid acidemia reversal with bicarbonate administration failed to provide any significant clinical differences or improved outcomes. This holds true for patients with severe DKA as well, albeit their sparse involvement in trials precludes any robust, evidence-based conclusion.
Transient paradoxical worsening of ketosis and increased need for potassium replacement were the major clinical issues found to be of concern. In the pediatric population, retrospective analysis yielded evidence of clinical harm including increased risk of cerebral edema and prolonged hospitalization with bicarbonate administration. The findings and conclusions drawn from the available literature are summarized in Table 2.
The most fundamental element upon which all else is built is a thorough history and physical exam. Patients who present with DKA characteristically develop a rapid onset of signs and symptoms that prompt initial evaluation. Classically, complaints of polyuria, polydipsia, weight loss, nausea and vomiting, abdominal pain and generalized weakness are among the most common symptoms.
Physical findings can include dry mucus membranes and poor skin turgor, tachycardia, Kussmaul respirations, fruity odor, and diffuse abdominal tenderness to palpation[ 5 ]. Caution needs to be exercised to assess for infection, as it is the most common cause of DKA.
Other factors such as medication compliance, changes in medications or dosages, myocardial infarction, and pancreatitis must be assessed as well. The triad of hyperglycemia, anion gap metabolic acidosis and ketonemia are the hallmark findings that help establish the diagnosis. The American Diabetes Association have proposed diagnostic criteria which stratify DKA severity based on pH, bicarbonate levels, and anion gap in addition to mental status changes[ 5 ].
As such, the measurement of arterial pH in the diagnosis of DKA became an important aspect of the management of these patients. Many protocols for the management of these patients, including the guidelines set forth by the American Diabetes Association, call for the serial measurement of several laboratory parameters including serum chemistry and blood gases as often as every two hours[ 5 ].
As such, attention shifted to the possible role of VBG sampling in the monitoring of DKA in an effort to avoid the complications and patient discomfort that accompanies repeated arterial punctures.
The authors universally agree that VBG analysis for pH and bicarbonate is an acceptable alternative of arterial blood gas ABG analysis.