Effect of chronic ß-blockade on the utility of an epinephrine-containing test dose to detect intravascular injection in nonsedated patients.

BACKGROUND AND OBJECTIVES: A test dose containing epinephrine is routinely used during epidural blockade to detect accidental intravenous needle or catheter placement before the administration of local anesthetics to avert local anesthetic systemic toxicity. ß-Blocker therapy may interfere with the expected hemodynamic response from an intravascular injection. This study describes a cohort of 24 patients and their response to an epinephrine test dose (ie, if expected increased heart rates during test-dose administration are valid in this population.) METHODS: Twenty-four nonsedated, chronically ß-blocked patients were enrolled in a prospective, order-randomized, crossover, double-blind study with injections of both placebo and a 15-µg epinephrine test dose in each individual. After injection into a peripheral vein, we observed blood pressure and pulse rate for 5 minutes, injected the other remaining solution (placebo or epinephrine), and observed hemodynamic parameters in the same fashion. RESULTS: Epinephrine raised the heart rate 17.8 beats per minute (bpm) (95% confidence interval [CI], 15.5-20.1) versus placebo 2.0 bpm (95% CI, - 0.3-4.3 P < 0.001) and the systolic blood pressure 23 mm Hg (95% CI, 17.2-28.9) versus placebo 4.4 (95% CI, - 1.5-10.3); P < 0.001 in our chronically ß-blocked population. A threshold increase of 20 bpm yielded a sensitivity of 37.5% (95% CI, 18.8%-59.4%) and specificity of 100% (95% CI, 85.8%-100%). Revising a threshold to include a change of 10 bpm or increase in systolic blood pressure of 15 mm Hg or greater yielded 100% (95% CI, 85.8%-100%) sensitivity and 87.5% (95% CI, 67.6%-97.3%) specificity. CONCLUSIONS: Epinephrine test-dose administration in nonsedated, chronically ß-blocked patients cannot distinguish intravenous injection at the classic threshold increase of 20 bpm. The response in individuals is varied, and thresholds for a positive test need revising for this population of patients on therapeutic ß-blockers.

Measured density and calculated baricity of custom-compounded drugs for chronic intrathecal infusion.

BACKGROUND AND OBJECTIVES: To minimize the frequency that intrathecal pumps require refilling, drugs are custom compounded at very high concentrations. Unfortunately, the baricity of these custom solutions is unknown, which is problematic, given baricity's importance in determining the spread of intrathecally administered drugs. Consequently, we measured the density and calculated the baricity of clinically relevant concentrations of multiple drugs used for intrathecal infusion. METHODS: Morphine, clonidine, bupivacaine, and baclofen were weighed to within 0.0001 g and diluted in volumetric flasks to produce solutions of known concentrations (morphine 1, 10, 25, and 50 mg/mL; clonidine 0.05, 0.5, 1, and 3 mg/mL; bupivacaine 2.5, 5, 10, and 20 mg/mL; baclofen 1, 1.5, 2, and 4 mg/mL). The densities of the solutions were measured at 37°C using the mechanical oscillation method. A "best-fit" curve was calculated for plots of concentration versus density for each drug. RESULTS: All prepared solutions of clonidine and baclofen were hypobaric. Higher concentrations of morphine and bupivacaine were hyperbaric, whereas lower concentrations were hypobaric. The relationship between concentration and density is linear for morphine (r > 0.99) and bupivacaine (r > 0.99) and logarithmic for baclofen (r = 0.96) and clonidine (r = 0.98). CONCLUSIONS: This is the first study to examine the relationship between concentration and density for custom drug concentrations commonly used in implanted intrathecal pumps. We calculated an equation that defines the relationship between concentration and density for each drug. Using these equations, clinicians can calculate the density of any solution made from the drugs studied here.

Prevention of local anesthetic systemic toxicity.

Although new drugs and techniques may improve outcomes when unintended high blood levels of local anesthetics occur, the primary focus of daily practice should remain the prevention of such events. Although adoption of no single "safety step" will reliably prevent systemic toxicity, the combination of several procedures seems to have reduced the frequency of systemic toxicity since 1981. These include the use of minimum effective doses, careful aspiration, and incremental injection, coupled with the use of intravascular markers when large doses are used. Epinephrine remains the most widely used and studied marker, but its reliability is impaired in the face of beta-blockade, anesthesia, advanced age, and active labor. As an alternative, the use of subtoxic doses of local anesthetics themselves can produce subjective symptoms in unpremedicated patients. Fentanyl has also been confirmed to produce sedation in pregnant women when used as an alternative. The use of ultrasound observation of needle placement and injection may be useful, but has also been reported as not completely reliable. Constant vigilance and suspicion are still needed along with a combination of as many of these safety steps as practical.

ASRA practice advisory on local anesthetic systemic toxicity.

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.