Kenneth Drasner

University of California, San Francisco, San Francisco, California, United States

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Publications (87)374.65 Total impact

  • Kenneth Drasner
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    ABSTRACT: Koller's 1884 report that cocaine induced corneal insensibility enabled ophthalmological procedures and marked the birth of clinical local anesthesia. Soon thereafter, Halsted and Hall produced peripheral nerve blocks while Corning and Bier used cocaine for spinal anesthesia. Toxicity stimulated the search for alternatives. The first new useful local anesthetic was the ester procaine, but its short duration of action limited clinical utility, a limitation overcome by tetracaine. Lidocaine, introduced in 1948, had an amide rather than an ester linkage, imparting greater stability and eliminating concern of allergic reactions from an ester breakdown product. Ironically, chloroprocaine reverted to the ester linkage, as its rapid degradation decreased risk of systemic toxicity. Regrettably, neural injury occurred when a large doses intended for the epidural space was apparently administered intrathecally. Bupivacaine, a longer-acting amide anesthetic was released in 1963. Associated untoward cardiac effects led to modifications in practice, while stereochemical strategies produced levobupivacaine and ropivacaine that have less affinity for cardiac sodium channels. Toxic reactions with spinal lidocaine resulted in its near abandonment as a spinal anesthetic. In 1998, Weinberg suggested that intravenous infusion of lipid could decrease the availability of local anesthetics and thereby treat systemic toxicity. As apparent from this history, toxicity, rather than efficacy, has directed the evolution of these compounds.
    No preview · Article · Oct 2013
  • Article: In reply.
    Kenneth Drasner · Weiming Ruan · Deborah French · Alicia Wong · Alan H B Wu

    No preview · Article · Sep 2012 · Anesthesiology
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    Weiming Ruan · Deborah French · Alicia Wong · Kenneth Drasner · Alan H B Wu
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    ABSTRACT: Lipid emulsion infusion reverses cardiac toxicity of local anesthetics. The predominant effect is likely creation of a "lipid sink." This in vitro study determined the extent to which Intralipid® (Fresenius Kabi, Uppsala, Sweden) and Lipofundin® (B. Braun Melsungen AG, Melsungen, Germany) sequester anesthetics from serum, and whether it varies with pH. Bupivacaine, ropivacaine, and mepivacaine were added to human drug-free serum (pH 7.4) at 10 μg/ml. The lipid emulsions were added, and the mixture shaken and incubated at 37°C. Lipid was removed by ultracentrifugation and drug remaining in the serum measured. Additional experiments were performed using 100 μg/ml bupivacaine and at pH 6.9. Lipofundin® extracted all three anesthetics to a greater extent than Intralipid® (34.7% vs..22.3% for bupivacaine, 25.8% vs..16.5% for ropivacaine, and 7.3% vs..4.7% for mepivacaine). By increasing either concentration of bupivacaine or lipid, there was an increase in drug extraction from serum. Adjusting the pH to 6.9 had no statistically significant effect on the percentage of bupivacaine sequestered. Bupivacaine, ropivacaine, and mepivacaine were sequestered to an extent consistent with their octanol:water partition constants (logP). In contrast with previous studies of extraction of lipids from buffer solutions, an emulsion containing 50% each of medium- and long-chain triglycerides extracted local anesthetics to a greater extent from human serum than one containing exclusively long-chain triglycerides, calling into question recent advanced cardiac life support guidelines for resuscitation from anesthetic toxicity that specify use of a long-chain triglyceride. The current data also do not support recent recommendations to delay administration until pH is normalized.
    Full-text · Article · Feb 2012 · Anesthesiology
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    ABSTRACT: Lipid infusion is useful in reversing cardiac toxicity of local anesthetics, and recent reports indicate it may be useful in resuscitation from toxicity induced by a variety of other drugs. While the mechanism behind the utility of lipid rescue remains to be fully elucidated, the predominant effect appears to be creation of a "lipid sink". Determine whether the extraction of drugs by lipid, and hence the clinical efficacy of lipid rescue in toxicological emergencies can be predicted by specific drug properties. Each drug investigated was added individually to human drug-free serum. Intralipid® was added to this drug-containing serum, shaken and then incubated at 37°C. The lipid was removed by ultracentrifugation and the concentration of drug remaining in the serum was measured by high-pressure liquid chromatography. In this in vitro model, the ability of lipid emulsion to bind a drug was largely dependent upon the drug's lipid partition constant. Additionally, using a multiple linear regression model, the prediction of binding could be improved by combining the lipid partition constant with the volume of distribution together accounting for approximately 88% of the variation in the decrease in serum drug concentration with the administration of lipid emulsion. The lipid partition constant and volume of distribution can likely be used to predict the efficacy of lipid infusion in reversing the cardiac toxicity induced by anesthetics or other medications.
    Full-text · Article · Nov 2011 · Clinical Toxicology
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    ABSTRACT: CONTEXT. Intralipid® infusion is useful in reversing cardiac and central nervous system toxicity of local anesthetic drugs, and recent reports suggest utility in other drug overdoses. CASE DETAILS. A 47-year-old man presented to the emergency department with hypotension and complete heart block 3 h after a sustained-release verapamil overdose. He was given supportive care including calcium and hyperinsulinemia/euglycemia therapy. Nineteen and 29 h post-ingestion, Intralipid® was administered as a bolus, followed by an infusion. OBJECTIVE. The objective of this study was to determine the serum verapamil concentrations before and after Intralipid® administration and to ascertain its clinical effects. DISCUSSION. It was found that administration of Intralipid® was followed by a decrease in verapamil concentration once the lipid had been removed from the sample, demonstrating that Intralipid® was effective in sequestering verapamil, effectively removing it from the serum, and supporting its use in the treatment of verapamil overdose. Intralipid® administration was associated with an increase in the patient's blood pressure, but because other vasoactive drugs were given at the same time, it was difficult to determine its relative contribution to clinical improvement.
    No preview · Article · Apr 2011 · Clinical Toxicology
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    Kenneth Drasner
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Preview · Article · Jan 2011
  • Kenneth Drasner

    No preview · Article · Jul 2010 · Anesthesiology
  • Andrew T Gray · Kenneth Drasner

    No preview · Article · Jun 2010 · Anesthesiology
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    Kenneth Drasner
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    ABSTRACT: The most feared complication associated with the administration of local anesthetics is the profound and potentially lethal effect that these agents can have on cardiac conduction and function. This review traces the evolution of local anesthetic systemic toxicity beginning with the early deaths associated with the introduction of cocaine into clinical practice. The development of bupivacaine is discussed, with particular emphasis on the delayed recognition and acceptance of its inherent cardiotoxicity. Finally, the origins of lipid resuscitation are reviewed with respect to their theoretical foundation, as well as the confluence of events and experimental investigations that delivered this therapy into clinical practice.
    Preview · Article · Mar 2010 · Regional anesthesia and pain medicine
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    ABSTRACT: The American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity assimilates and summarizes current knowledge regarding the prevention, diagnosis, and treatment of this potentially fatal complication. It offers evidence-based and/or expert opinion-based recommendations for all physicians and advanced practitioners who routinely administer local anesthetics in potentially toxic doses. The advisory does not address issues related to local anesthetic-related neurotoxicity, allergy, or methemoglobinemia. Recommendations are based primarily on animal and human experimental trials, case series, and case reports. When objective evidence is lacking or incomplete, recommendations are supplemented by expert opinion from the Practice Advisory Panel plus input from other experts, medical specialty groups, and open forum. Specific recommendations are offered for the prevention, diagnosis, and treatment of local anesthetic systemic toxicity.
    Full-text · Article · Mar 2010 · Regional anesthesia and pain medicine
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    ABSTRACT: Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes.
    No preview · Article · Mar 2010 · Regional anesthesia and pain medicine
  • K. Drasner

    No preview · Article · Jan 2010 · Obstetric Anesthesia Digest
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    K Drasner

    Preview · Article · Jul 2009 · BJA British Journal of Anaesthesia

  • No preview · Article · Sep 2008 · Regional Anesthesia and Pain Medicine
  • Kenneth Drasner · Richard Smiley

    No preview · Article · Mar 2008 · Anesthesiology
  • K Drasner

    No preview · Article · Oct 2005 · Anesthesia & Analgesia
  • Kenneth Drasner

    No preview · Article · Apr 2005 · Anesthesia & Analgesia
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    Kenneth Drasner

    Preview · Article · Mar 2005 · Anesthesia & Analgesia
  • Kenneth Drasner

    No preview · Article · Sep 2004 · Anesthesia & Analgesia
  • Masahiko Taniguchi · Andrew W Bollen · Kenneth Drasner
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    ABSTRACT: Neurologic deficits after apparent intrathecal injection of 3% Nesacaine-CE intended for epidural administration created concern about the potential toxicity of chloroprocaine and the preservative sodium bisulfite. Although bisulfite-free formulations of chloroprocaine were subsequently introduced into clinical practice, the relative toxicities of this anesthetic and preservative were never clearly established. The current studies used a relevant functional and histologic model to investigate the intrathecal neurotoxicity of these two compounds. In the first experiment, rats implanted with intrathecal catheters were given one of two commercially available solutions of chloroprocaine, one of which contained sodium bisulfite; control animals received saline. Animals were assessed for sensory impairment 7 days after administration using the tail-flick test and were killed to obtain histologic specimens to quantify nerve injury. In the second experiment, identical methodology was used to investigate the effects of freshly prepared solutions of chloroprocaine, chloroprocaine with sodium bisulfite, sodium bisulfite, and saline. The two experiments yielded similar results. In experiment 1, tail-flick latencies and nerve injury scores after administration of plain chloroprocaine were significantly greater than those of chloroprocaine containing bisulfite. Injury scores for animals receiving chloroprocaine with bisulfite were elevated compared with those for animals given saline. In experiment 2, animals receiving plain chloroprocaine developed elevations in tail-flick latencies and nerve injury scores that were significantly greater than those for all other groups. Nerve injury scores with chloroprocaine containing bisulfite were greater than with saline or bisulfite alone. Tail-flick latencies and nerve injury scores with bisulfite alone were similar to those with saline. Clinical deficits associated with unintentional intrathecal injection of chloroprocaine likely resulted from a direct effect of the anesthetic, not the preservative. The data also suggest that bisulfite can reduce neurotoxic damage induced by intrathecal local anesthetic.
    No preview · Article · Feb 2004 · Anesthesiology

Publication Stats

3k Citations
374.65 Total Impact Points

Institutions

  • 1988-2012
    • University of California, San Francisco
      • Department of Anesthesia and Perioperative Care
      San Francisco, California, United States
  • 2005
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 1996-1997
    • Universität Basel
      Bâle, Basel-City, Switzerland
  • 1992
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
    • Northwestern University
      Evanston, Illinois, United States