Physical and Chemical Compatibility of Medications Commonly Used in Critically Ill Patients With Balanced Crystalloids: A Systematic Review.

OBJECTIVE: Evaluate available evidence of physical and/or chemical compatibility of commonly used medications in critically ill patients with balanced crystalloids. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were queried from inception to September 2022. STUDY SELECTION AND DATA EXTRACTION: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies reporting physical and/or chemical compatibility data between 50 selected medications and balanced crystalloids were included. A previously designed tool to assess risk of bias was adapted for use. DATA SYNTHESIS: Twenty-nine studies encompassing 39 (78%) medications and 188 unique combinations with balanced crystalloids were included. Combinations included 35 (70%) medications with lactated Ringer's, 26 (52%) medications with Plasma-Lyte, 10 (20%) medications with Normosol, and one (2%) medication with Isolyte. Studies commonly evaluated physical and chemical compatibility (55.2%). More medications were evaluated via Y-site than admixture. Incompatibilities were identified in 18% of combinations comprising 13 individual drugs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This systematic review evaluates the compatibility of select critical care medications with balanced crystalloid solutions. Results may be used as a tool to guide clinicians on balanced crystalloid compatibility, potentially increasing ubiquitous use and reducing patient exposure to normal saline. CONCLUSION AND RELEVANCE: Data are limited regarding chemical/physical compatibility of commonly used medications in critically ill patients with balanced crystalloids. Additional compatibility studies are warranted, particularly methodologically rigorous studies assessing Plasma-Lyte, Normosol, and Isolyte. Of the evaluated medications, there was a low frequency of incompatibilities with balanced crystalloids.

A Comprehensive, Retrospective Analysis of Variables for Potential Mortality Impact in Patients With Thermal or Inhalation Injury.

Age, percentage TBSA burned, and the presence of inhalation injury have been used historically in the prediction of mortality in thermally injured patients despite other factors being also associated with mortality. Recent literature has identified novel factors associated with increased length of stay (LOS) and may provide a better prediction model for mortality in burn patients. The study objective was to perform a subset analysis of a multitude of known and novel variables for potential association with mortality. Demographics and injury characteristics along with during stay variables were collected and analyzed. This study is a re-analysis of a retrospective study examining variables associated with increased LOS. Of the 629 patients screened, 396 were included in the analysis. After univariable analysis, 35 variables had significant associations with mortality, including age, house fire, acute kidney injury, heart failure, inhalation injury, and history of diabetes. After multivariable analysis, the best performing model included heart failure, acute kidney injury, admission Glasgow Coma Scale score, and revised Baux score. Quantile analysis of age revealed greater than 60 years was most predictive of mortality. The best multivariable model for patients greater than 60 years old included heart failure, vasopressor use, acute respiratory distress syndrome, and TBSA burned. Considering only variables present on admission, the best multivariable model for patients greater than 60 years old included heart failure, % TBSA burned, and inhalation injury. The addition of variables into current prediction models and databases may be warranted.

Protein requirements for critically ill ventilator-dependent patients with COVID-19.

BACKGROUND: Recent studies indicate critically ill patients with coronavirus disease 2019 (COVID-19) are hypermetabolic; however, protein requirements in critically ill COVID-19 patients are unknown. Our intent was to evaluate the nitrogen accretion response to varying protein intakes for critically ill ventilator-dependent patients with COVID-19. METHODS: Adult patients (age ≥ 18 years) with COVID-19, admitted to the intensive care unit (ICU) and who required mechanical ventilation were retrospectively evaluated. Patients received continuous enteral nutrition (EN), including supplemental protein boluses, and had a 24-h urine collection for determination of nitrogen balance (NBAL). Data are expressed as mean ± SD with a P-value < .05 as significant. RESULTS: Twenty-two patients provided 29 NBAL determinations. Protein intake from EN and protein supplements was 0.9 ± 0.7 g/kg/day at the time of the NBAL with an NBAL of -12.1 ± 10.9 g/day at 7 ± 4 days in the ICU. Combined caloric intake from EN and propofol at the time of the NBAL was 12 ± 8 kcal/kg/day. Nitrogen equilibrium (NBAL of -4 g/day or better) occurred in five patients. Patients achieving nitrogen equilibrium received more protein than those with a negative NBAL (1.2 ± 0.4 g/kg/day vs 0.8 ± 0.8 g/kg/day, P = .046). The linear regression for NBAL in response to graded increases in protein intake was as follows: NBAL = 8.5 × protein intake (g/kg/day) - 18.8 (r = 0.450, P < .001). CONCLUSION: Critically ill ventilator-dependent patients with COVID-19 exhibit significant variability in nitrogen accretion response to increases in protein intake and often have a markedly negative NBAL.

Impact of Propofol Sedation upon Caloric Overfeeding and Protein Inadequacy in Critically Ill Patients Receiving Nutrition Support.

Propofol, a commonly used sedative in the intensive care unit, is formulated in a 10% lipid emulsion that contributes 1.1 kcals per mL. As a result, propofol can significantly contribute to caloric intake and can potentially result in complications of overfeeding for patients who receive concurrent enteral or parenteral nutrition therapy. In order to avoid potential overfeeding, some clinicians have empirically decreased the infusion rate of the nutrition therapy, which also may have detrimental effects since protein intake may be inadequate. The purpose of this review is to examine the current literature regarding these issues and provide some practical suggestions on how to restrict caloric intake to avoid overfeeding and simultaneously enhance protein intake for patients who receive either parenteral or enteral nutrition for those patients receiving concurrent propofol therapy.

Cenobamate: A New Adjunctive Agent for Drug-Resistant Focal Onset Epilepsy.

OBJECTIVE: To review the pharmacology, efficacy, and safety of oral cenobamate in the treatment of uncontrolled focal epilepsy. DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: cenobamate, Xcopri, and YKP3089. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 2000 and April 2020 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In a phase 2 trial, cenobamate reduced the median percentage change in seizure frequency from baseline by 56% compared with 22% for placebo (P < 0.0001). In another phase 2 trial of multiple cenobamate doses, cenobamate reduced seizure frequency by 36% (P = 0.0071) in the 100-mg group and 55% (P < 0.0001) in both the 200- and 400-mg groups, compared to 24% with placebo. Adverse effects of cenobamate appear to be similar to those of other antiseizure medications and primarily affect the neurological system. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: In patients taking antiseizure medications who continue to have focal seizures, cenobamate has efficacy at multiple doses and is generally well tolerated. Cenobamate may be distinguished from other antiseizure medications by high rates of seizure freedom not seen in previous placebo-controlled trials, which has the potential to significantly improve quality of life. However, despite this efficacy, Drug Reaction with Eosinophilia and Systemic Symptoms may remain a significant concern with cenobamate. CONCLUSION: As seen in clinical trials, cenobamate as an adjunctive, once-daily treatment represents an efficacious and generally well-tolerated therapy for patients with drug-resistant focal epilepsy.

Improvement in Protein Delivery for Critically Ill Patients Requiring High-Dose Propofol Therapy and Enteral Nutrition.

BACKGROUND: Patients with traumatic brain (TBI) injury often require a high dosage of propofol, which can provide an excessive caloric intake. We evaluated our strategy of using liquid protein supplement boluses concurrently with high protein-containing enteral nutrition (EN) formulas and formula rate reduction to avoid caloric overfeeding and inadequate protein intake. METHODS: Adult patients (aged >17 years) with TBI admitted to the trauma intensive care unit (TICU) who received concurrent propofol and EN were retrospectively reviewed. Caloric intakes from propofol and EN were obtained. Actual protein intake was compared with projected protein intakes from high protein content and standard protein content enteral formulas when given at an isocaloric intake. RESULTS: Fifty-one patients were enrolled. Average caloric intake from propofol was 356 ± 243 kcal/d or 5 ± 3 kcal/kg/d (range, <1-15 kcal/kg/d). Daily EN caloric intake ranged from 7 ± 4 kcal/kg/d (day 2) to 16 ± 9 kcal/kg/d (day 5; P < .001). Average protein intake ranged from 0.6 ± 0.4 g/kg/d (day 2) to 1.5 ± 0.7 g/kg/d (day 5; P < .001). The modified EN strategy resulted in daily delivery of 24%-38% more protein than an isocaloric regimen with a high protein-content formula and twice as much protein than the standard protein-content formula (P < .001). CONCLUSION: The strategy of providing an EN regimen comprised liquid protein boluses, and high and very high protein-containing EN formulas at a reduced rate improved protein delivery without caloric overfeeding.