Jonathan M. Weimer

Brachial plexus root injection in a human cadaver model: Injectate distribution and effects on the neuraxis

Background The potential for injection into the brachial plexus root at cervical levels must be considered during interscalene block or chronic pain interventions in the neck, but this phenomenon has not been well studied. In this investigation, we performed injections into the brachial plexus roots of unembalmed cadavers, with real-time ultrasound guidance, to evaluate the proximal and distal spread of the injected fluids, the potential of the injectate to reach the neuraxis, and whether the injectate could migrate into the actual substance of the spinal cord itself. Methods A solution of particulate dye mixed with local anesthetic was injected into 8 brachial plexus roots at a lower cervical level, in unembalmed cadaver specimens, utilizing an automated pump and pressure monitor. Two injections were made adjacent to nerve roots as controls. The specimens were then dissected, and gross and microscopic analysis utilized to determine the distribution of the dye and the structures affected. Results The mean peak pressure achieved during plexus root injections was 48.9 psi. After injections into the plexus root, dye was evident within the neural tissue at the level of injection and spread primarily distally in the plexus. In 1 of 8 injections into the brachial plexus root, the dye in the injectate spread proximally into the spinal canal, but in none of the injections was the spinal cord affected by the dye. Conclusions Injection directly into the neural tissue of a brachial plexus root in a cadaver model produced high pressures suggestive of intrafascicular injection and widespread flow of the injectate through the distal brachial plexus. However, proximal movement of the dye-containing injectate was more restricted, with only 1 of the injections leading to epidural spread and no apparent effects on the spinal cord.

Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape.

To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs) taken up via endocytic pathways must efficiently transport across the cell membrane and subsequently escape from the secondary endosomes. We hypothesized that the biomechanical and thermodynamic interactions of NPs with plasma and endosomal membrane lipids are involved in these processes. Using model plasma and endosomal lipid membranes, we compared the interactions of cationic NPs composed of poly(d,l-lactide-co-glycolide) modified with the dichain surfactant didodecyldimethylammonium bromide (DMAB) or the single-chain surfactant cetyltrimethylammonium bromide (CTAB) vs anionic unmodified NPs of similar size. We validated our hypothesis in doxorubicin-sensitive (MCF-7, with relatively fluid membranes) and resistant breast cancer cells (MCF-7/ADR, with rigid membranes). Despite their cationic surface charges, DMAB- and CTAB-modified NPs showed different patterns of biophysical interaction: DMAB-modified NPs induced bending of the model plasma membrane, whereas CTAB-modified NPs condensed the membrane, thereby resisted bending. Unmodified NPs showed no effects on bending. DMAB-modified NPs also induced thermodynamic instability of the model endosomal membrane, whereas CTAB-modified and unmodified NPs had no effect. Since bending of the plasma membrane and destabilization of the endosomal membrane are critical biophysical processes in NP cellular uptake and endosomal escape, respectively, we tested these NPs for cellular uptake and drug efficacy. Confocal imaging showed that in both sensitive and resistant cells DMAB-modified NPs exhibited greater cellular uptake and escape from endosomes than CTAB-modified or unmodified NPs. Further, paclitaxel-loaded DMAB-modified NPs induced greater cytotoxicity even in resistant cells than CTAB-modified or unmodified NPs or drug in solution, demonstrating the potential of DMAB-modified NPs to overcome the transport barrier in resistant cells. In conclusion, biomechanical interactions with membrane lipids are involved in cellular uptake and endosomal escape of NPs. Biophysical interaction studies could help us better understand the role of membrane lipids in cellular uptake and intracellular trafficking of NPs.

Withdrawal of Life-sustaining Therapy in Patients With Intracranial Hemorrhage: Self-fulfilling Prophecy or Accurate Prediction of Outcome?

Objectives:Withdrawal of life-sustaining therapy may lead to premature limitations of life-saving treatments among patients with intracranial hemorrhage, representing a self-fulfilling prophecy. We aimed to determine whether our algorithm for the withdrawal of life-sustaining therapy decision would accurately identify patients with a high probability of poor outcome, despite aggressive treatment. Design:Retrospective analysis of prospectively collected data. Setting:Tertiary-care Neuro-ICU. Patients:Intraparenchymal, subdural, and subarachnoid hemorrhage patients. Interventions:Baseline demographics, clinical status, and hospital course were assessed to determine the predictors of in-hospital mortality and 12-month death/severe disability among patients receiving maximal therapy. Multivariable logistic regression models developed on maximal therapy patients were applied to patients who underwent withdrawal of life-sustaining therapy to predict their probable outcome had they continued maximal treatment. A validation cohort of propensity score–matched patients was identified from the maximal therapy cohort, and their predicted and actual outcomes compared. Measurements and Main Results:Of 383 patients enrolled, there were 128 subarachnoid hemorrhage (33.4%), 134 subdural hematoma (35.0%), and 121 intraparenchymal hemorrhage (31.6%). Twenty-six patients (6.8%) underwent withdrawal of life-sustaining therapy and died, 41 (10.7%) continued maximal therapy and died in hospital, and 316 (82.5%) continued maximal therapy and survived to discharge. The median predicted probability of in-hospital death among withdrawal of life-sustaining therapy patients was 35% had they continued maximal therapy, whereas the median predicted probability of 12-month death/severe disability was 98%. In the propensity-matched validation cohort, 16 of 20 patients had greater than or equal to 80% predicted probability of death/severe disability at 12 months, matching the observed outcomes and supporting the strength and validity of our prediction models. Conclusions:The withdrawal of life-sustaining therapy decision may contribute to premature in-hospital death in some patients who may otherwise have been expected to survive to discharge. However, based on probability models, nearly all of the patients who underwent withdrawal of life-sustaining therapy would have died or remained severely disabled at 12 months had maximal therapy been continued. Withdrawal of life-sustaining therapy may not represent a self-fulfilling prophecy.

Dural Traction a Possible Cause of Hemodynamic Changes During Single-Level Transforaminal Lumbar Interbody Fusion

BACKGROUND Lumbar spinal surgery may be associated with electrophysiologic and hemodynamic abnormalities during the procedure. CASE DESCRIPTION A 58-year-old man with grade II L4-5 spondylolisthesis and degenerative changes underwent single-level transforaminal lumbar interbody fusion. During decompression of the L4 foramina, distraction of the disc space, and placement of the interbody cage and pedicle screws, episodes of extreme bradycardia with up to 5 seconds of asystole were detected on electrocardiogram and invasive hemodynamic monitoring. The events correlated with and possibly could have been a result of traction on the dura mater. CONCLUSIONS Anesthesia providers should be aware of electrophysiologic and hemodynamic abnormalities during lumbar spinal surgery and the need to respond appropriately with sympathomimetic or vagolytic interventions.