Pharmacologic Therapy for Spinal Cord Injury.

Neuroprotective strategies aimed at preventing secondary neurologic injury following acute spinal cord injury remain an important area of clinical, translational, and basic science research. Despite recent advancement in the understanding of basic mechanisms of primary and secondary neurologic injury, few pharmacologic agents have shown consistent promise in improving neurologic outcomes following SCI in large randomized clinical trials. The authors review the existing literature and clinical guidelines for pharmacologic therapy investigated for managing acute SCI, including corticosteroids, GM-1 ganglioside (Sygen), Riluzole, opioid antagonists, Cethrin, minocycline, and vasopressors for mean arterial pressure augmentation. Therapies for managing secondary effects of SCI, such as bradycardia, are discussed. Current clinical trials for pharmacotherapy and cellular transplantation following acute SCI are also reviewed. Despite the paucity of current evidence for clinically beneficial post-SCI pharmacotherapy, future research efforts will hopefully elucidate promising therapeutic agents to improve neurologic function.

Correlation of intraventricular nicardipine for refractory vasospasm in aneurysmal subarachnoid hemorrhage with improved neurophysiology on intracranial multimodality monitoring: illustrative case.

BACKGROUND: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage can lead to considerable mortality and morbidity affecting the intracranial vessels, leading to delayed cerebral ischemia and stroke. Therapeutic options for patients with treatment-refractory vasospasm are limited, particularly in the setting of significant cardiopulmonary disease. Administration of nicardipine, a calcium channel blocker, into the intrathecal space may represent a potential treatment option for this population. OBSERVATIONS: A 56-year-old woman had treatment-refractory vasospasm, severe acute respiratory distress syndrome, and Takotsubo cardiomyopathy. As an adjunct to vasopressor administration and endovascular intraarterial calcium channel blocker administration, the patient received intraventricular nicardipine. The patient demonstrated improved neurophysiology on invasive multimodality neuromonitoring, with increased cerebral blood flow and oxygenation as a result of intraventricular nicardipine administration. LESSONS: Intraventricular nicardipine can be used as rescue therapy for patients with treatment-refractory cerebral vasospasm. This case demonstrates that intrathecal nicardipine may prevent delayed ischemic neurological deficits and improve outcomes.

An Audit and Comparison of pH, Measured Concentration, and Particulate Matter in Mannitol and Hypertonic Saline Solutions.

Background: The preferred hyperosmolar therapy remains controversial. Differences in physical properties such as pH and osmolality may be important considerations in hyperosmolar agent selection. We aimed to characterize important physical properties of commercially available hyperosmolar solutions. Methods: We measured pH and concentration in 37 commonly-used hyperosmolar solutions, including 20 and 25% mannitol and 3, 5, 14.6, and 23.4% hypertonic saline. pH was determined digitally and with litmus paper. Concentration was determined by freezing point and vapor pressure osmometry. Salinity/specific gravity was measured with portable refractometry. Particulate matter was analyzed with filtration and light microscopy and with dynamic light scattering nephelometry. Results: pH of all solutions was below physiological range (measured range 4.13-6.80); there was no correlation between pH and solution concentration (R 2 = 0.005, p = 0.60). Mannitol (mean 5.65, sd 0.94) was less acidic than hypertonic saline (5.16, 0.60). 14/59 (24%) pH measurements and 85/111 concentration measurements were outside manufacturer standards. All 36/36 mannitol concentration measurements were outside standards vs. 48/72 (67%) hypertonic saline (p < 0.0001). All solutions examined on light microscopy contained crystalline and/or non-crystalline particulate matter up to several hundred microns in diameter. From nephelometry, particulate matter was detected in 20/22 (91%) solutions. Conclusion: We present a novel characterization of mannitol and hypertonic saline. Further research should be undertaken, including research examining development of acidosis following hyperosmolar therapy, the relevance of our findings for dose-response, and the clinical relevance of particulate matter in solution.

Emergent Reversal of Direct Oral Anticoagulants Permitting Neurosurgical Intervention for Nonhemorrhagic Pathology.

BACKGROUND: Direct oral anticoagulants (DOACs) are becoming the medication of choice for the management of venous thromboembolism and stroke prevention in atrial fibrillation because of simplified dosing, a more predictive pharmacokinetic profile, and better clinical outcomes when compared with traditional vitamin K antagonists. Recently, reversal agents for DOACs have been approved by the U.S. Food and Drug Administration for use in managing life-threatening or uncontrolled bleeding; however, for acute nonhemorrhagic conditions requiring surgical intervention, such as acute hydrocephalus requiring ventriculostomy, there is little evidence to help guide appropriate management for patients on DOACs. CASE DESCRIPTION: We report the use of andexanet alfa to counteract rivaroxaban treatment in a 28-year-old woman who developed herniation syndrome and acute hydrocephalus from a cerebellar tumor. CONCLUSIONS: We describe how appropriate timing of administration of the DOAC reversal agent may permit urgent neurosurgical intervention.

Visual compatibility of i.v. medications routinely used in bone marrow transplant recipients.

PURPOSE: The visual compatibility of i.v. medications routinely used in bone marrow transplant recipients was studied. METHODS: A total of 17 drug combinations were tested using simulated Y-site administration. Medications were prepared to the standard concentrations used at University of Utah Health Care and infused at the appropriate rate. For each combination, the two drugs had 99 cm of shared tubing. At the end of the shared tubing was a 0.8-microm filter disk. All of the drug combinations were tested in triplicate. After the infusion was complete, each filter was bubble-point tested to ensure filter integrity and to remove residual solution. The tubing and dried filter were examined by eye as well as a magnification microscope. Drug combinations were considered incompatible if a precipitate or color change was visible to the naked eye during filtration or if the number of particles observed under the microscope exceeded 12 particles of > or =10 microm in diameter per milliliter of solution or if 2 or more particles of > or =25 microm in diameter per milliliter of solution were observed, per guidelines established by the United States Pharmacopeia for large-volume injections. RESULTS: Of the 17 drug combinations tested, 5 combinations were observed to be visually incompatible. All of the incompatible combinations included acyclovir as the primary infusion. Acyclovir was incompatible with cyclosporine, diphenhydramine, gentamicin, granisetron, and metoclopramide. CONCLUSION: Of the 17 drug combinations tested, 5 combinations were observed to be visually incompatible during simulated Y-site injection. The combinations found to be visually incompatible included acyclovir with cyclosporine, diphenhydramine, gentamicin, granisetron, or metoclopramide.

Visual compatibility of caspofungin acetate with commonly used drugs during simulated Y-site delivery.

PURPOSE: The physical compatibility of i.v. caspofungin with other commonly used i.v. medications was tested. METHODS: Two methods were used to combine caspofungin and the secondary drugs. For drugs administered by i.v. push, caspofungin was delivered through a poly-vinyl chloride (PVC) i.v. solution set with secondary drugs injected into the Y-site of the i.v. extension set. For drugs given by i.v. infusion (over 10 minutes), secondary drugs were infused into the Y-site of the i.v. solution set through microbore PVC tubing. The two drugs shared 39 in of tubing. Attached to each end of the i.v. extension set were 0.8-mum filter disks. All drug combinations were tested three times; after each infusion, the filters were bubble-point tested. Drug combinations were considered physically compatible if no visible precipitate was seen and no color change was noted by the unaided eye during the infusion, or if the number of particles found on the filter under a microscope did not exceed the number stated in United States Pharmacopeia guidelines for particulate levels of large-volume parenteral fluids. RESULTS: A total of 8 of the 31 drugs tested (acyclovir, ceftriaxone, cefazolin, clindamycin, furosemide, heparin, pantoprazole, and piperacillin-tazobactam) were found to be physically incompatible with caspofungin. CONCLUSION: Caspofungin acetate was physically compatible during Y-site injection with 23 of 31 medications tested.