Robert A. Peterfreund

Goal: To develop a compact, real-time microfluidic spectroscopy system capable of simultaneously measuring the concentrations of multiple solutes flowing together through a single fluid pathway with high temporal resolution. Methods: The measurement system integrates a Z-flow cell and dual-wavelength LED light sources with a compact spectrophotometer. The experimental setup consisted of two clinical infusion pumps delivering distinct marker dyes through a common fluid pathway composed of a clinical manifold and a single lumen of a clinical intravascular catheter, while a third pump delivered an inert carrier fluid. Concentration measurements of the mixed dyes were performed at high-frequency sampling intervals, with dynamic pump rate adjustments to evaluate the system's ability to detect real-time changes in solute concentration. A MATLAB-based control application enabled automated data acquisition, processing, and system control to enhance experimental efficiency. Results: The system accurately measured solute concentrations, capturing temporal variations with high precision. It demonstrated high reproducibility with a standard error of the mean no larger than $0.19 \,\mu \mathrm{g}\mathrm{/}\mathrm{m}\mathrm{L}$ for Erioglaucine and $1.32 \,\mu \mathrm{g}\mathrm{/}\mathrm{m}\mathrm{L}$ for Tartrazine at steady state, and high accuracy with a maximum deviation of $0.21 \,\mu \mathrm{g}\mathrm{/}\mathrm{m}\mathrm{L}$ for Erioglaucine and $0.5 \,\mu \mathrm{g}\mathrm{/}\mathrm{m}\mathrm{L}$ for Tartrazine from the expected steady-state concentrations. Conclusions: This system enables continuous, real-time monitoring of multiple solutes in dynamic flow conditions, offering a portable solution with high sensitivity to temporal concentration changes—advancing beyond traditional static fluid measurement methods.

Managing delivery of complex multidrug infusions in anesthesia and critical care presents a significant clinical challenge. Current practices relying on manual control of infusion pumps often result in unpredictable drug delivery profiles and dosing errors—key issues highlighted by the United States Food and Drug Administration (FDA). To address these issues, we introduce the SMART (synchronized‐pump management algorithms for reliable therapies) framework, a novel approach that leverages low Reynolds number drug transport physics and machine learning to accurately manage multidrug infusions in real‐time. SMART is activated based on the Shafer number (), a novel non‐dimensional number that quantifies the relative magnitude of a drug's therapeutic action timescale to its transport timescale within infusion manifolds. SMART is useful when , where drug transport becomes the rate limiting step in achieving the desired therapeutic effects. When activated, SMART monitors multidrug concentrations within infusion manifolds and leverages this information to perform end‐to‐end management of drug delivery using an ensemble of deterministic and deep reinforcement learning (RL) decision networks. Notably, SMART RL networks employ differentially sampled split buffer architecture that accelerates learning and improves performance by seamlessly combining deterministic predictions with RL experience during training. SMART deployed in standalone infusion pumps under simulated clinical conditions outperformed state‐of‐the‐art manual control protocols. This framework has the potential to revolutionize critical care by enhancing accuracy of medication delivery and reducing cognitive workloads. Beyond critical care, the ability to accurately manage multi‐liquid delivery via complex manifolds will have important bearings for manufacturing and process control.

A patient with lumbar spine stenosis presented for lumbar spine decompression, clearly stating a preference for spinal anesthesia (SA) over general anesthesia (GA). Surgery was performed under uneventful SA without sedation. The patient recovered from surgery quickly and without incident, requiring no postoperative opioid analgesia. What data support administering SA for lumbar spine surgery? A literature search found nine recently published reviews favoring SA over GA. These reviews cited many of the same, older, flawed, primary research reports. Although choosing SA was reasonable, our literature analysis suggests blind reliance on summary conclusions of reviews and meta‐analyses may be misleading.

Critically ill or anesthetized patients commonly receive pump-driven intravenous infusions of potent, fast-acting, short half-life medications for managing hemodynamics. Stepwise dosing, e.g. over 3–5 min, adjusts physiologic responses. Flow rates range from < 0.1 to > 30 ml/h, depending on pump type (large volume, syringe) and drug concentration. Most drugs are formulated in aqueous solutions. Hydrophobic drugs are formulated as lipid emulsions. Do the physical and chemical properties of emulsions impact delivery compared to aqueous solutions? Does stepwise dose titration by the pump correlate with predicted plasma concentrations? Precise, gravimetric, flow rate measurement compared delivery of a 20% lipid emulsion (LE) and 0.9% saline (NS) using different pump types and flow rates. We measured stepwise delivery and then computed predicted plasma concentrations following stepwise dose titration. We measured the pharmacokinetic coefficient of short-term variation, (PK-CV), to assess pump performance. LE and NS had similar mean flow rates in stepwise rate increments and decrements between 0.5 and 32 ml/h and continuous flows 0.5 and 5 ml/h. Pharmacokinetic computation predictions suggest delayed achievement of intended plasma levels following dose titrations. Syringe pumps exhibited smaller variations in PK-CV than large volume pumps. Pump-driven deliveries of lipid emulsion and aqueous solution behave similarly. At low flow rates we observed large flow rate variability differences between pump types showing they may not be interchangeable. PK-CV analysis provides a quantitative tool to assess infusion pump performance. Drug plasma concentrations may lag behind intent of pump dose titration.

Ketamine produces antidepressant effects in patients with treatment-resistant depression, but its usefulness is limited by its psychotropic side effects. Ketamine is thought to act via NMDA receptors and HCN1 channels to produce brain oscillations that are related to these effects. Using human intracranial recordings, we found that ketamine produces gamma oscillations in prefrontal cortex and hippocampus, structures previously implicated in ketamine’s antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, previously proposed as a mechanism for its dissociative effects. We analyzed oscillatory changes after subsequent propofol administration, whose GABAergic activity antagonizes ketamine’s NMDA-mediated disinhibition, alongside a shared HCN1 inhibitory effect, to identify dynamics attributable to NMDA-mediated disinhibition versus HCN1 inhibition. Our results suggest that ketamine engages different neural circuits in distinct frequency-dependent patterns of activity to produce its antidepressant and dissociative sensory effects. These insights may help guide the development of brain dynamic biomarkers and novel therapeutics for depression.

Spinal anesthesia (SA) has been utilized for lumbar surgical procedures; however, postdural puncture headache (PDPH) and subdural hemorrhage (SDH) are potential consequences. We present the case of a 76-year-old with progressive neurogenic claudication secondary to lumbar spinal stenosis who received SA for a 2-level lumbar posterior decompression. After decompression, the site of dural puncture from a 24-gauge Sprotte spinal needle was identified. Our intraoperative image demonstrates the submillimeter dural defect that can potentially engender complications as significant as PDPH and/or SDH. We recommend searching for, and preemptively sealing, the dural puncture site when SA is used for lumbar spine surgery.

Vagus nerve injury may complicate carotid endarterectomy (CEA). The recurrent laryngeal nerve (RLN) branches from the vagus nerve, innervating the ipsilateral vocal cord. Vagus nerve injury can cause vocal cord dysfunction. Intraoperative vocal cord monitoring can detect vagus nerve injury during CEA. A patient with distorted neck anatomy from radiotherapy to treat oropharyngeal cancer and resultant right vocal cord paralysis required left CEA. Anticipating difficult neck dissection risking vagus nerve damage with associate RLN malfunction, we added vocal cord electromyography (EMG) to routine CEA electroencephalography (EEG). We recommend vocal cord EMG in anatomically complex CEA to avoid vagus nerve injury.

Anesthesiologists at our hospital commonly administer spinal anesthesia for routine lumbar spine surgeries. Anecdotal impressions suggested that patients received fewer anesthesia–administered intravenous medications, including vasopressors, during spinal versus general anesthesia. We hypothesized that data review would confirm these impressions. The objective was to test this hypothesis by comparing specific elements of spinal versus general anesthesia for 1–2 level open lumbar spine procedures. Retrospective single institutional study. Academic medical center, operating rooms. Consecutive patients (144 spinal and 619 general anesthesia) identified by automatic structured query of our electronic anesthesia record undergoing lumbar decompression, foraminotomy or microdiscectomy by one surgeon under general or spinal anesthesia. Spinal or general anesthesia. Numbers of medications administered during the case. Anesthesiologists administered in the operating room a total of 10 ± 2 intravenous medications for general anesthetics and 5 ± 2 medications for spinal anesthetics (-5, 95% CI -5 to -4, p<0.001, univariate analysis). Multivariable analysis supported this finding (spinal versus general anesthesia: -4, 95% CI -5 to -4, p<0.001). Spinal anesthesia patients were less likely to receive ephedrine, or phenylephrine (by bolus or by infusion) (all p<0.001, Chi-squared test). Spinal anesthesia patients were also less likely to receive labetolol or esmolol (both p = 0.002, Fishers’ Exact test). No neurologic injuries were attributed to, or masked by, spinal anesthesia. Three spinal anesthetics failed. For routine lumbar surgery in our cohort, spinal compared to general anesthesia was associated with significantly fewer drugs administered during a case and less frequent use of vasoactive agents. Safety implications include greater hemodynamic stability with spinal anesthesia along with reduced risks for medication error and transmission of pathogens associated with medication administration.