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Safety and Efficacy of 23.4% Sodium Chloride Administered via Peripheral Venous Access for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation

Faiver, Laura; Hensler, David; Rush, Stephen C; Kashlan, Osama; Williamson, Craig A; Rajajee, Venkatakrishna
BACKGROUND:Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access. METHODS:We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes. RESULTS:We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (- 13 mm Hg [central] vs. - 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration. CONCLUSIONS:Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.
PMID: 34173156
ISSN: 1556-0961
CID: 4965572

Dose-Response Relationships for Meningioma Radiosurgery

Sethi, Rajni A; Rush, Stephen C; Liu, Shian; Sethi, Suresh A; Parker, Erik; Donahue, Bernadine; Narayana, Ashwatha; Silverman, Joshua; Kondziolka, Douglas; Golfinos, John G
OBJECTIVE: Dose-response relationships for meningioma radiosurgery are poorly characterized. We evaluated determinants of local recurrence for meningiomas treated with Gamma Knife radiosurgery (GKRS), to guide future treatment approaches to optimize tumor control. MATERIALS AND METHODS: A total of 101 consecutive patients (108 tumors) who underwent GKRS for benign, atypical, or malignant meningiomas between 1998 and 2011 were studied. Local recurrence was assessed. Cox proportional hazards and logistic regression analyses were used to determine the association of patient-related, tumor-related, and treatment-related characteristics with local recurrence. Acute and late toxicity was evaluated. RESULTS: World Health Organization (2007 classification) tumor grade was I (82%), II (11%), or III (7%). Median dose was 14 Gy (range, 10 to 18 Gy) for grade I tumors and 16 Gy (range, 12 to 20 Gy) for grade II and III tumors. Median follow-up was 25 months (maximum, 17 y). Two- /5-year actuarial local control rates were 100%/98% for grade I tumors and 76%/56% for grade II/III tumors. Higher tumor grade and lower GKRS dose were associated with local failure. In this cohort, there was a 42% relative reduction in local recurrence for each 1 Gy of dose escalation. CONCLUSIONS: Treatment was well tolerated with no moderate or severe toxicity. Tumor control was excellent in benign tumors and suboptimal in higher grade tumors. Because the main determinant of local recurrence was GKRS dose, we recommend dose escalation for atypical or malignant tumors to doses between 16 and 20 Gy where critical structures allow.
PMID: 26595685
ISSN: 1537-453x
CID: 1856322

Evolution of pararescue medicine during operation enduring freedom

Rush, Stephen; Boccio, Eric; Kharod, Chetan U; D'Amore, Jason
This article highlights recent advances made in U.S. Air Force Pararescue Medical Operations in relation to tactical evacuation procedures. Most of these changes have been adopted and adapted from civilian medicine practice, and some have come from shared experiences with partner nations. Patient assessment includes a more comprehensive evaluation for hemorrhage and indications for hemorrhagic control. Ketamine has replaced morphine and fentanyl as the primary sedative used during rapid sequence intubation and procedural sedation. There has been an increasing use of the bougie to clear an airway or nasal cavity that becomes packed with debris. Video laryngoscopy provides advantages over direct laryngoscopy, especially in situations where there are environmental constraints such as the back of a Pave Hawk helicopter. Intraosseous access has become popular to treat and control hemorrhagic shock when peripheral intravenous access is impractical or impossible. Revisions to patient treatment cards have improved the efficacy and compliance of documentation and have made patient handoff more efficient. These improvements have only been possible because of the concerted efforts of U.S. Air Force and partner platforms operating in Afghanistan.
PMID: 25747635
ISSN: 0026-4075
CID: 1495782

Cinnarizine for Sea Sickness During a Remote Pacific Ocean Rescue Mission

Lyon, Regan F; Rush, Stephen C; Roland, J Thomas Jr; Jethanamest, Daniel; Schwan, Christopher P; Kharon, Chetan U
Motion sickness can be a limiting factor for sea and air missions. We report the experience of a Pararescue (PJ) team on a Pacific Ocean rescue mission in which motion sickness was prevalent. Cinnarizine, an antagonist of H1-histamine receptors, was used to treat affected PJs. We also report findings of a survey of PJs regarding motion sickness. A family of four on a disabled sailboat 900 miles off the coast of Mexico sent out a distress call because their 1-year-old daughter became severely ill with fever and diarrhea. Four PJs were deployed on a C-130, performed a free-fall parachute insertion into the ocean, and boarded the sailboat. All four PJs experienced onset of motion sickness at some point during the early part of the mission and symptoms persisted through the first 24 hours. Three PJs experienced ongoing nausea, vomiting, dizziness, and sensory imbalances. The captain of the sailboat offered the three sick PJs approximately 18mg of cinnarizine two or three times a day with relief of symptoms and improvement on operational effectiveness. A new, anonymous, voluntary survey of Air National Guard PJs and combat rescue officers revealed that 78.4% of Operators have experienced motion sickness at sea. We discuss the current theories on motion sickness, the effect of motion sickness on operational effectiveness, and research on treatment of motion sickness, including the medication cinnarizine.
PMID: 26125158
ISSN: 1553-9768
CID: 1650502

A review of the evolution of intraosseous access in tactical settings and a feasibility study of a human cadaver model for a humeral head approach

Rush, Stephen; D'Amore, Jason; Boccio, Eric
In the tactical setting, intraosseous (IO) access has become popular to treat hemorrhagic shock when peripheral intravenous access is difficult or impractical. The traditional sites most commonly used by combat medics, corpsmen, and Pararescuemen (PJs) include the sternum and tibial tuberosity. Recent studies have shown that the humeral head (HH) is an appropriate and effective access site for IO infusion and fluid resuscitation in the clinical setting. In this procedural feasibility study, we assessed the ability of 26 U.S. Air Force PJs to perform HH IO placement on fresh, unfixed human cadavers over two consecutive cadaver lab training sessions. Following a formal didactic session, which highlighted proper patient positioning and technique, the PJs were instructed to attempt to place an IO needle using both a drill and manual driver. Once performed, correct placement was reviewed by a physician and confirmed by aspiration of bone marrow. Rates of success were calculated on first and second pass. First pass success rates were 96% and 90.5% for the drill and driver, respectively. Both devices achieved 100% success by the second pass. Military field personnel would benefit from a HH approach, especially in the care and management of patients of explosive injuries.
PMID: 25102545
ISSN: 0026-4075
CID: 1195562

The accuracy of predicting survival in individual patients with cancer

Kondziolka, Douglas; Parry, Phillip V; Lunsford, L Dade; Kano, Hideyuki; Flickinger, John C; Rakfal, Susan; Arai, Yoshio; Loeffler, Jay S; Rush, Stephen; Knisely, Jonathan P S; Sheehan, Jason; Friedman, William; Tarhini, Ahmad A; Francis, Lanie; Lieberman, Frank; Ahluwalia, Manmeet S; Linskey, Mark E; McDermott, Michael; Sperduto, Paul; Stupp, Roger
Object Estimating survival time in cancer patients is crucial for clinicians, patients, families, and payers. To provide appropriate and cost-effective care, various data sources are used to provide rational, reliable, and reproducible estimates. The accuracy of such estimates is unknown. Methods The authors prospectively estimated survival in 150 consecutive cancer patients (median age 62 years) with brain metastases undergoing radiosurgery. They recorded cancer type, number of brain metastases, neurological presentation, extracranial disease status, Karnofsky Performance Scale score, Recursive Partitioning Analysis class, prior whole-brain radiotherapy, and synchronous or metachronous presentation. Finally, the authors asked 18 medical, radiation, or surgical oncologists to predict survival from the time of treatment. Results The actual median patient survival was 10.3 months (95% CI 6.4-14). The median physician-predicted survival was 9.7 months (neurosurgeons = 11.8 months, radiation oncologists = 11.0 months, and medical oncologist = 7.2 months). For patients who died before 10 months, both neurosurgeons and radiation oncologists generally predicted survivals that were more optimistic and medical oncologists that were less so, although no group could accurately predict survivors alive at 14 months. All physicians had individual patient survival predictions that were incorrect by as much as 12-18 months, and 14 of 18 physicians had individual predictions that were in error by more than 18 months. Of the 2700 predictions, 1226 (45%) were off by more than 6 months and 488 (18%) were off by more than 12 months. Conclusions Although crucial, predicting the survival of cancer patients is difficult. In this study all physicians were unable to accurately predict longer-term survivors. Despite valuable clinical data and predictive scoring techniques, brain and systemic management often led to patient survivals well beyond estimated survivals.
PMID: 24160479
ISSN: 0022-3085
CID: 687512

Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study

Sheehan, Jason P; Starke, Robert M; Mathieu, David; Young, Byron; Sneed, Penny K; Chiang, Veronica L; Lee, John Y K; Kano, Hideyuki; Park, Kyung-Jae; Niranjan, Ajay; Kondziolka, Douglas; Barnett, Gene H; Rush, Stephen; Golfinos, John G; Lunsford, L Dade
Object Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). Results Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Conclusions Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.
PMID: 23621595
ISSN: 0022-3085
CID: 335232

Forward aeromedical evacuation: a brief history, lessons learned from the Global War on Terror, and the way forward for US policy [Historical Article]

Olson, Chris M Jr; Bailey, Jeffrey; Mabry, Robert; Rush, Stephen; Morrison, Jonathan J; Kuncir, Eric J
PMID: 23883897
ISSN: 2163-0755
CID: 759392

Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery

Mathew, Maya; Tam, Moses; Ott, Patrick A; Pavlick, Anna C; Rush, Stephen C; Donahue, Bernadine R; Golfinos, John G; Parker, Erik C; Huang, Paul P; Narayana, Ashwatha
The anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab has been shown to improve survival in patients with metastatic non-CNS melanoma. The purpose of this study was to investigate the efficacy of CTLA-4 inhibitors in the treatment of metastatic melanoma with limited brain metastases treated with stereotactic radiosurgery (SRS). Between January 2008 and June 2011, 58 patients with limited brain metastases from melanoma were treated with SRS with a median dose of 20 Gy delivered to the 50% isodose line (range, 15-20 Gy). In 25 patients, ipilimumab was administered intravenously at a dose of 3 mg/kg over 90 min every 3 weeks for a median of four doses (range, 1-8). Local control (LC), freedom from new brain metastases, and overall survival (OS) were assessed from the date of the SRS procedure. The median LC, freedom from new brain metastases, and OS for the entire group were 8.7, 4.3, and 5.9 months, respectively. The cause of death was CNS progression in all but eight patients. Six-month LC, freedom from new brain metastases, and OS were 65, 35, and 56%, respectively, for those who received ipilimumab and 63, 47, and 46% for those who did not (P=NS). Intracranial hemorrhage was noted in seven patients who received ipilimumab compared with 10 patients who received SRS alone (P=NS). In this retrospective study, administration of ipilimumab neither increased toxicity nor improved intracerebral disease control in patients with limited brain metastases who received SRS.
PMID: 23462208
ISSN: 0960-8931
CID: 315922

Recent consideration in tactical medicine

Rush, Stephen
A philosophical approach to tactical and remote medicine should be reflected in the gear (e.g., equipment and technology) chosen as well as the protocols used. The gear needs to be lightweight and small volume. Asmuch as possible, it should have multiple uses, and there should be no redundancy with other items. When modern technology (e.g., hemostatic gauze, pulse oximeters, etc.) allows it to have unique applications, it should be used. Otherwise, if simple basic gear works, it should remain a staple (e.g., cravats). Protocols should reflect the goal to provide thorough care in an efficient manner. They should be straightforward and scaleable and be capable of being trained in a fashion that will allow them to become automatic under duress. These guiding principles establish a basis from which the Special Operations Forces/Tactical Medic or PJ can operate to maximal effectiveness. This article will describe current thinking in Pararescue as it relates to gear and protocols.
PMID: 23817879
ISSN: 1553-9768
CID: 3663902