Changes in vitamin D metabolites at the time of critical illness and 6 months later-A prospective observational study.

BACKGROUND: Despite multiple studies suggesting that low 25(OH)D-vitamin levels are associated with worse outcomes in critically ill individuals, attempts to mitigate the outcomes by fixed dose enteral supplementation unguided by baseline or target blood levels have been unsuccessful. Since a single measurement of 25(OH)D may not optimally reflect an individual's vitamin D status, we studied the plasma concentration of different vitamin D metabolites and their recovery during and following resolution of acute critical illness. METHODS: A prospective observational study including patients 18 years and older admitted to a mixed medical-surgical ICU in Reykjavik, Iceland, located at a high-northern altitude (64° N). Vitamin D metabolites were measured at three timepoints; On admission (S1), 3-5 days following admission (S2) and after recovery from acute illness (median 178 days) (S3). Concentrations of total 25(OH)D-vitamin, cholecalciferol (D3 ), total 24,25(OH)D-vitamin, vitamin D binding protein (VDBP) were measured with LC-tandem mass spectrometry (LC-MS/MS) and free 25-(OH)D was measured with enzyme-linked immunosorbent assay. RESULTS: Most individuals were vitamin D deficient when assessed during critical illness, with 25(OH)D-vitamin levels under 30 ng/ml for 37/40 individuals at timepoint S1 and 34/38 at S2. After recovery, 18/30 patients were deficient at S3. Levels of all vitamin D metabolites measured were low during critical illness but rose substantially following resolution of acute illness. No strong correlation was found between markers of acute illness severity or duration and resolution of vitamin D metabolites in the interval between acute illness and recovery. CONCLUSIONS: In critically ill patients, levels of multiple vitamin D metabolites are low but substantial recovery occurs following resolution of acute illness. It is unclear whether a single metabolite is sufficient to assess vitamin D status of critically ill patients and guide potential supplementation.

Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management.

Hyperammonemia occurs frequently in the critically ill but is largely confined to patients with hepatic dysfunction or failure. Non-hepatic hyperammonemia (NHHA) is far less common but can be a harbinger of life-threatening diagnoses that warrant timely identification and, sometimes, empiric therapy to prevent seizures, status epilepticus, cerebral edema, coma and death; in children, permanent cognitive impairment can result. Subsets of patients are at particular risk for developing NHHA, including the organ transplant recipient. Unique etiologies include rare infections, such as with Ureaplasma species, and unmasked inborn errors of metabolism, like urea cycle disorders, must be considered in the critically ill. Early recognition and empiric therapy, including directed therapies towards these rare etiologies, is crucial to prevent catastrophic demise. We review the etiologies of NHHA and highlight the first presentation of it associated with a concurrent Ureaplasma urealyticum and Mycoplasma hominis infection in a previously healthy individual with polytrauma. Based on this clinical review, a diagnostic and treatment algorithm to identify and manage NHHA is proposed.

Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations From Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III.

OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.

Perioperative Considerations for Evolving Artificial Pancreas Devices.

Type 1 diabetes mellitus is a lifelong condition. It requires intensive patient involvement including frequent glucose measurements and subcutaneous insulin dosing to provide optimal glycemic control to decrease short- and long-term complications of diabetes mellitus without causing hypoglycemia. Variations in insulin pharmacokinetics and responsiveness over time in addition to illness, stress, and a myriad of other factors make ideal glucose control a challenge. Control-to-range and control-to-target artificial pancreas devices (closed-loop artificial pancreas devices [C-APDs]) consist of a continuous glucose monitor, response algorithm, and insulin delivery device that work together to automate much of the glycemic management for an individual while continually adjusting insulin dosing toward a glycemic target. In this way, a C-APD can improve glycemic control and decrease the rate of hypoglycemia. The MiniMed 670G (Medtronic, Fridley, MN) system is currently the only Food and Drug Administration-cleared C-APD in the United States. In this system, insulin delivery is continually adjusted to a glucose concentration, and the patient inputs meal-time information to modify insulin delivery as needed. Data thus far suggest improved glycemic control and decreased hypoglycemic events using the system, with decreased need for patient self-management. Thus, the anticipated use of these devices is likely to increase dramatically over time. There are limited case reports of safe intraoperative use of C-APDs, but the Food and Drug Administration has not cleared any device for such use. Nonetheless, C-APDs may offer an opportunity to improve patient safety and outcomes through enhanced intraoperative glycemic control. Anesthesiologists should become familiar with C-APD technology to help develop safe and effective protocols for their intraoperative use. We provide an overview of C-APDs and propose an introductory strategy for intraoperative study of these devices.

A Misguided Contraindication: International Normalized Ratio in Acute Liver Failure Precluding Thrombolysis for Massive Pulmonary Embolism: A Case Report.

Massive pulmonary embolism and its treatment with thrombolysis both carry grave risks. Optimal management hinges on determining the risk-to-benefit ratio of thrombolytic administration. For patients with liver dysfunction, assessing bleeding risk is challenging because they may have elevations in the international normalized ratio yet be hypercoagulable. We describe a patient with massive pulmonary embolism and new-onset liver failure, who-absent contraindications-warranted thrombolysis. Initial laboratory values, however, revealed an elevated international normalized ratio, which precluded lysis, despite a hypercoagulable Thromboelastogram. We believe that viscoelastic testing of coagulation is essential for evaluating coagulation in liver dysfunction, particularly when considering thrombolysis.

Complete Neurologic Recovery From Extreme Hypoglycemia Secondary to Cardiogenic Liver Failure: A Case Report.

Cardiogenic shock from acute severe mitral valve regurgitation can cause acute liver failure due to hypoperfusion. Impaired liver glycogenesis can then lead to profound hypoglycemia. The time frame for restoring normoglycemia without neurologic sequelae is not clearly established in humans. Thus, the clinical decision to provide further resuscitation in the setting of extreme hypoglycemia mainly depends on the patient's overall clinical condition, provider opinion, and/or institutional practice. Here, we report a case where the patient made complete neurologic recovery from extreme hypoglycemia (<5 mg/dL by central laboratory testing) secondary to acute cardiogenic shock and liver failure.