Diabetes insipidus related to sedation in the intensive care unit: A review of the literature.

PURPOSE: To identify cases of diabetes insipidus (DI) related to sedation in the ICU to determine which medications pose the greatest risk and understand patterns of presentation. MATERIALS AND METHODS: We searched PubMed, Embase, Scopus, Google Scholar, and Web of Science. Search terms included "polyuria," "diabetes insipidus," "hypnotics and sedatives," "sedation," as well as individual medications. Case reports or series involving DI or polyuria related to sedation in the ICU were identified. RESULTS: We identified 21 cases of diabetes insipidus or polyuria in the ICU attributed to a sedative. Dexmedetomidine was implicated in 42.9% of cases, followed by sevoflurane (33.3%) and ketamine (23.8%). Sevoflurane was implicated in all 7 cases in which it was used (100%; 95% CI 59.0%, 100.0%), dexmedetomidine in 9 of 11 cases (81.8%; 95% CI 48.2, 97.7), and ketamine in 5 of 9 cases (55.6%; 95% CI 21.2%, 86.3%). CONCLUSIONS: Awareness of the potential for sedatives to cause DI may lead to greater identification with swifter medication discontinuation and subsequent resolution of DI.

Unilateral Hypoglossal Nerve Palsy in a Patient with a Difficult Airway Requiring Prolonged Intubation.

Isolated cranial nerve injury is a very rare complication of anesthesia. Specifically, hypoglossal nerve palsy affects mobility of the tongue and basic functions of swallowing and speech, and injury can be associated with placement and/or positioning of the endotracheal tube. Many etiologies are described that are unrelated to anesthesia such as tumors, stroke, trauma, or surgical dissection. Identification of hypoglossal neuropraxic-type injury from compression or stretching during anesthetic procedures can be difficult and tends to be a diagnosis of exclusion. Here, we present a case of a unilateral isolated hypoglossal nerve palsy following prolonged intubation in a surgery that involved large fluid shifts resulting in tongue swelling, in which establishment of the airway was initially difficult requiring two attempts. We suggest it is equally as possible that stretch injury occurred during airway instrumentation versus prolonged compression of the nerve between the endotracheal tube and the hyoid bone, possibly relating to a swollen tongue. We outline some treatments that have been used in previous reports and analyze their relation to improvements in symptoms. We conclude that instrumentation of the airway and prolonged intubation are both potential risk factors for hypoglossal nerve palsy, and identification of these risk factors can improve patient care by prompting patient discussions, guiding intraoperative management, and initiating earlier therapies.

Transient Protein Expression by Agroinfiltration in Lettuce.

Current systems of recombinant protein production include bacterial, insect, and mammalian cell culture. However, these platforms are expensive to build and operate at commercial scales and/or have limited abilities to produce complex proteins. In recent years, plant-based expression systems have become top candidates for the production of recombinant proteins as they are highly scalable, robust, safe, and can produce complex proteins due to having a eukaryotic endomembrane system. Newly developed "deconstructed" viral vectors delivered via Agrobacterium tumefaciens (agroinfiltration) have enabled robust plant-based production of proteins with a wide range of applications. The leafy Lactuca sativa (lettuce) plant with its strong foundation in agriculture is an excellent host for pharmaceutical protein production. Here, we describe a method for agroinfiltration of lettuce that can rapidly produce high levels of recombinant proteins in a matter of days and has the potential to be scaled up to an agricultural level.

Efficient agroinfiltration of plants for high-level transient expression of recombinant proteins.

Mammalian cell culture is the major platform for commercial production of human vaccines and therapeutic proteins. However, it cannot meet the increasing worldwide demand for pharmaceuticals due to its limited scalability and high cost. Plants have shown to be one of the most promising alternative pharmaceutical production platforms that are robust, scalable, low-cost and safe. The recent development of virus-based vectors has allowed rapid and high-level transient expression of recombinant proteins in plants. To further optimize the utility of the transient expression system, we demonstrate a simple, efficient and scalable methodology to introduce target-gene containing Agrobacterium into plant tissue in this study. Our results indicate that agroinfiltration with both syringe and vacuum methods have resulted in the efficient introduction of Agrobacterium into leaves and robust production of two fluorescent proteins; GFP and DsRed. Furthermore, we demonstrate the unique advantages offered by both methods. Syringe infiltration is simple and does not need expensive equipment. It also allows the flexibility to either infiltrate the entire leave with one target gene, or to introduce genes of multiple targets on one leaf. Thus, it can be used for laboratory scale expression of recombinant proteins as well as for comparing different proteins or vectors for yield or expression kinetics. The simplicity of syringe infiltration also suggests its utility in high school and college education for the subject of biotechnology. In contrast, vacuum infiltration is more robust and can be scaled-up for commercial manufacture of pharmaceutical proteins. It also offers the advantage of being able to agroinfiltrate plant species that are not amenable for syringe infiltration such as lettuce and Arabidopsis. Overall, the combination of syringe and vacuum agroinfiltration provides researchers and educators a simple, efficient, and robust methodology for transient protein expression. It will greatly facilitate the development of pharmaceutical proteins and promote science education.

Agroinfiltration as an Effective and Scalable Strategy of Gene Delivery for Production of Pharmaceutical Proteins.

Current human biologics are most commonly produced by mammalian cell culture-based fermentation technologies. However, its limited scalability and high cost prevent this platform from meeting the ever increasing global demand. Plants offer a novel alternative system for the production of pharmaceutical proteins that is more scalable, cost-effective, and safer than current expression paradigms. The recent development of deconstructed virus-based vectors has allowed rapid and high-level transient expression of recombinant proteins, and in turn, provided a preferred plant based production platform. One of the remaining challenges for the commercial application of this platform was the lack of a scalable technology to deliver the transgene into plant cells. Therefore, this review focuses on the development of an effective and scalable technology for gene delivery in plants. Direct and indirect gene delivery strategies for plant cells are first presented, and the two major gene delivery technologies based on agroinfiltration are subsequently discussed. Furthermore, the advantages of syringe and vacuum infiltration as gene delivery methodologies are extensively discussed, in context of their applications and scalability for commercial production of human pharmaceutical proteins in plants. The important steps and critical parameters for the successful implementation of these strategies are also detailed in the review. Overall, agroinfiltration based on syringe and vacuum infiltration provides an efficient, robust and scalable gene-delivery technology for the transient expression of recombinant proteins in plants. The development of this technology will greatly facilitate the realization of plant transient expression systems as a premier platform for commercial production of pharmaceutical proteins.