Permanent implantation of peripheral nerve stimulator for combat injury-related ilioinguinal neuralgia.

A peripheral nerve stimulator (PNS) can be an alternative for long-term pain relief refractory to conventional therapeutic modalities. We present a case of chronic incapacitating ilioinguinal neuralgia, which was successfully managed with permanent implantation of a peripheral nerve stimulator. A 26-year-old active duty African American man was referred to the University Pain Clinic with left ilioinguinal neuralgia due to shrapnel injury during his military service 6 years prior to his visit. Most of the shrapnel were surgically removed, but the patient subsequently developed left lower abdominal pain. Multiple surgeries, including inguinal herniorrhaphy, varicocelectomy, and orchiectomy, failed to provide satisfactory relief of his neuralgia. Other therapies tried resulting in limited outcomes were multiple ilioinguinal nerve blocks and cryoanalgesia. A trial of PNS was successful and the implantation of permanent leads was carried out. At his 3-month visit, the patient reported to have minimal pain, was tapered off oral analgesics, was able to return to work, and had resumed his normal daily activities. Recent technological advances in programming software and surgical techniques have led to renewed interest in PNS for the treatment of chronic refractory peripheral nerve injury. Despite our limited understanding of its exact mechanism of action, it can be considered as a therapeutic potential for a few carefully selected, intractable cases. Its minimally invasive and reversible features make PNS a favorable option for these patients. The stringent and rigorous screening procedures for suitable candidacy, documentation of previously failed treatments, psychiatric evaluation, and 3-5 days of preplacement trial, improve the success rate.

Managing difficult airway in patients with post-burn mentosternal and circumoral scar contractures.

Securing the airway is a crucial aspect during reconstructive surgeries of patients with extensive post-burn mentosternal scar contractures; however, the American Society of Anesthesiologists Difficult Airway Management Algorithm recommendation of initial direct laryngoscopy may not be appropriate for these complicated patients. Consequently, there is a significant risk for failure of intubation and airway emergency. We suggest that initial attempts at securing the airway be made with indirect laryngoscopy. Many airway techniques have been effectively used in burn patients, but the role of awake blind or fiberoptic bronchoscopy, although well established in the non-burn population, has yet to be evaluated in burn patients. We report a case series of successful management of difficult airways with fiberoptic bronchoscopy in patients with varying degrees of post-burn head and neck scar contractures.

Population pharmacokinetics and pharmacodynamics of brief etomidate infusion in healthy volunteers.

This study established the pharmacokinetic and pharmacodynamic relationships of the bispectral index (BIS) and Observer's Assessment of Alertness/Sedation (OAA/S) scale with effect site drug concentrations during and after brief etomidate infusion. Eighteen American Society of Anesthesiologists status I or II volunteers received etomidate (0.2%) infusion at 5 mg/min until the loss of eyelash reflexes, and spontaneous recovery was allowed. Data for plasma etomidate concentrations, BIS, and OAA/S were collected every minute and analyzed by NONMEM. A 2-compartment pharmacokinetic model and a pharmacodynamic sigmoid E(max) model fit the data best, with volumes of distribution at central and peripheral compartments of 4.45 and 74.90 L, respectively, and systemic and intercompartmental clearances of 0.63 and 3.16 L/min, respectively. t(1/2)k(e0) was 1.550 min. EC(50) values were 0.526 and 0.554 µg/mL, and gamma values were 2.25 and 6.24 for BIS and OAA/S, respectively. The prediction probability between OAA/S and BIS was 0.8. The slopes of the curves suggest that BIS is a better monitor of depth of sedation and hypnosis, whereas OAA/S may be more useful for monitoring sleep versus wakefulness. These results should be interpreted within the context of short-term etomidate infusion of less than 10 minutes.

Population pharmacokinetics of a propofol bolus administered in patients with major burns.

OBJECTIVE: In operating theaters and burn units, propofol is commonly used for sedation and anesthesia in patients with major burns. This study determined the population pharmacokinetics of propofol in burns and identified clinically significant covariates. METHOD: Seventeen adults, age 42±10 (mean±SD) years, with 41±19% total body surface area burns, were enrolled at 16±14 days after-burn. Non-burn adults (n=19) served as controls. After an intravenous bolus of 2mg/kg propofol, the plasma concentration was determined at designated times for up to 4.5h. Concentration-time profiles were analyzed using nonlinear mixed-effect modeling. RESULTS: A three-compartment model gave the best fit. The volume of distribution of the central compartment (V(1)) was considerably greater in the burned than non-burned group (48.4 L vs. 27.6 L, respectively). The clearances of the central (CL(1)) and slow peripheral (CL(3)) compartments were higher in burn patients (4.2 L/min vs. 1.7 L/min and 3.6 L/min vs. 1.1 L/min, respectively). Adding the covariates BURN to V(1), CL(1), and CL(3) and WT (weight) to CL(1) significantly improved the model performance. CONCLUSION: The pharmacokinetic characteristics of a propofol bolus administered in patients with major burns were enhanced clearance and expanded volume of distribution. BURN and WT were the important covariates. For sedation or anesthesia induction, a higher than recommended dose of propofol may be required to maintain therapeutic plasma drug concentrations in patients with severe burns. Vigilance regarding the burned individual and careful titration of hypnotics to the desired effect cannot be overemphasized.

Pharmacokinetic characteristics of bolus-administered mannitol in patients undergoing elective craniotomy.

To better understand mannitol pharmacokinetics, the authors constructed and compared population models for high-versus low-dose bolus infusions in humans. Patients (aged 18-75, American Society of Anesthesiologists physical status 1-3) scheduled for elective craniotomy with an anticipated need for intraoperative mannitol were randomly assigned to receive either 0.5 (n = 10) or 1.0 (n = 12) g/kg of 20% mannitol over 15 minutes. Serial blood samples were collected at the predetermined intervals over 12 hours. Plasma mannitol concentrations were measured by gas chromatography and subjected to pharmacokinetic analysis; a 3-compartment model best described mannitol disposition characteristics. Weight and dose were the important covariates for rapid peripheral volume of distribution (V2) and central clearance (CL1), respectively. Estimated population means were 2.80, 8.86, and 12.0 L for central (V1), rapid (V2), and slow (V3) volumes of distribution, respectively. Clearances of the central compartments (CL1) were 0.07 versus 0.04 L/min in the high-versus low-dose group, respectively. Thus, mannitol kinetics can be considered as nonlinear. Clearances of the rapid peripheral (CL2) and slow peripheral compartments (CL3) were identical (2.07 and 0.16 L/min) in both. The current weight-based dosing guidelines yielded greater than expected plasma drug concentrations in obese patients.

Comparative population pharmacokinetics of fentanyl using non-linear mixed effect modeling: burns vs. non-burns.

OBJECTIVE: Fentanyl is a commonly used analgesic and sedative for the burned in the operating theater as well as the burn care units. The aim of this study was to characterize fentanyl population pharmacokinetics in burns and to identify clinically significant covariates. METHOD: Twenty adults, aged 37+/-3 years, with 49+/-4% (mean+/-S.E.) total body surface area burn, were enrolled at 17+/-3 days after the injury. Twenty non-burn adults served as controls. After an intravenous bolus of 200 mcg fentanyl, the plasma concentrations were sequentially determined up to 4.5 h. Concentration-time profiles were subjected to non-linear mixed effect modeling. Cardiac indices were estimated with esophageal Doppler monitor. RESULTS: Burned patients have higher cardiac index than the non-burned. Three-compartment model was the best fit. The volumes of distribution were considerably expanded in all three compartments (27.9 L vs. 63.4 L, 64.7 L vs. 92.9 L, 153 L vs. 301 L, respectively) compared to the non-burned. BURN was the single most important covariate significantly improving the model. CONCLUSION: The primary effect of burn trauma on fentanyl pharmacokinetics is substantially expanded volumes of distribution, i.e., dilutional. Difference in simulation, however, was insufficient to explain the augmented resistance to fentanyl, implying the importance of titrating analgesics to the clinical effect.

Propofol clearance and volume of distribution are increased in patients with major burns.

Propofol pharmacokinetics were examined in 17 adults with major burns during the hyperdynamic convalescent phase. Eighteen nonburned surgical patients served as controls. After a 2-mg/kg intravenous dose of propofol, blood samples were collected at multiple time points. Noncompartmental methods were used to calculate the pharmacokinetic parameters. The following indices were higher in burns than controls: propofol clearance (64+/-17 vs 29+/-4 mL/kg/min, P<.001) and volume of distribution (8+/-3 vs 4+/-1 L/kg, P<.001). The area under the curve was smaller in burns (556+/-152 vs 1193+/-183 microg/mL h, P<.001). The higher clearance of propofol in burned patients may imply that these patients require higher doses or infusion rates of propofol to attain a target plasma concentration or pharmacodynamic effect.

Burns in epilepsy: seven years of experience from the Hallym Burn Center in Korea.

The objective of this retrospective epidemiological study was to identify the characteristics of burn injuries of seizure disorder patients in Korea, with the goal of developing programs to prevent or reduce the frequency and morbidity of such injuries. We reviewed the medical records of 34 acutely burned, epileptic-seizure patients who were admitted to a single regional burn center unit during the 7 years between January 1997 and April 2003, all of whom had been burned during an epileptic seizure. The most commonly associated seizure type was generalized tonic-clonic, followed by absence and complex partial. Females predominated in all age groups. There were more seizures in the morning hours between 3 and 10 am. The mean age was 43 +/- 16 years. Seizures occurred at home, while the patient was conducting daily household chores. Scalding was the most common injury, leaving small-but-deep wounds that required a mean hospital stay of 37 +/- 27 days. Typically, upper limbs and trunk were affected. To implement a successful burns injury-prevention program, patients with epilepsy should be better recognized as a high-risk group. Specific passive as well as active recommendations are suggested based on the epidemiologic features of seizure disorder patients in Korea.

Bispectral index does not correlate with observer assessment of alertness and sedation scores during 0.5% bupivacaine epidural anesthesia with nitrous oxide sedation.

The bispectral index (BIS) has been used as a measure of the degree of sedation and level of hypnosis for IV hypnotics and sedatives, potent volatile anesthetics. We evaluated the effect of increasing concentrations of nitrous oxide (N2O) on BIS and compared it with the Observer's Assessment of Alertness and Sedation (OAA/S) scale in patients undergoing regional anesthesia. We studied 48 unpremedicated, ASA physical status I-II adult patients scheduled for lower extremity surgery under lumbar epidural anesthesia. N2O was given in oxygen to achieve measured end-tidal concentrations of 33%, 50%, and 67% N2O by a tight-fitting facemask, and each N2O concentration was maintained for 20 min. Paired measurements of BIS and OAA/S scores were obtained just before each increase in N2O concentration. Forty of the 48 subjects completed the study. Increasing N(2)O concentrations produced no changes in BIS despite a significant decrease in OAA/S scores at 50% and 67% N2O concentrations. The prediction probability for BIS and OAA/S calculated by Somers' d(x.y) were 0.60 and 0.84, respectively. Anesthesiologists should be aware that the BIS monitor may not be sensitive enough to provide an adequate measure of the depth of sedation and hypnosis when using N2O alone for sedation. It may be better to monitor sedation clinically (e.g., with the OAA/S scale) to determine the dose requirement and the adequacy of depth of sedation and hypnosis.

Face burns caused by flambé drinks.

This study was conducted to identify the epidemiology of face burns in Korean adults caused by flambé drinks in the hope of developing preventive programs. We reviewed the medical records of 25 patients with burns caused by flame drinks that were admitted to the Hallym Burn Centre, Hangang Sacred Heart Hospital, Seoul, Korea, during the 30-month period of July 2002 to December 2004. The injuries occurred while drinking and spilling the whisky on the flame (68%) during the hours of social gathering and festivity. There were more men than women (male:female ratio=21:4); the mean age was 27.5+/-5.7 years (mean 27, range 21-43 years). Alcohol flames inflicted superficial (56%) to mid-second-degree burns in a relatively small area of body (TBSA 3.2+/-3.0%). The head was most commonly involved, followed by the upper extremity and trunk. All patients except two were treated with observation and daily dressing changes only. The mean length of hospital stay was 12.1+/-6.5 (10, 5-25) days. Long-term cosmetic outcomes were excellent. Some victims suffered mild corneal (n=4) and ear (n=6) burns, without permanent sequelae. Post-traumatic stress disorder and depression also were reported. Burn injuries induced by flambé drinks may be prevented by increasing public awareness about its danger and the potential risk for corneal and facial burns and by implementing a safety policy. All the involved parties--public, distillers, and bar and restaurant management--need to coordinate their efforts achieve a reduction in injuries.

A retrospective analysis of 19,157 burns patients: 18-year experience from Hallym Burn Center in Seoul, Korea.

This is a retrospective, epidemiological study of 19,157 acute burn patients admitted to the Hallym Burn Centre, Hangang Sacred Heart Hospital, Seoul, Korea, during the period 1986-2003. The study was conducted to identify characteristics of burn patients that could lead to development of preventive programs to reduce both the frequency and mortality of burn injury. The majority of patients admitted had relatively minor burns, which were treated conservatively. Males predominated in all age groups with a summer peak seasonal variation. Typical burn in the children <5 years of age was a scald injury, occurring at home, affecting upper limbs and resulting in a relatively short hospital stay. Electrical burns due to steel chopsticks and steam burns due to electric rice cookers were also found in this age group. Adult burns, affecting upper and lower limbs, were caused by flames, hot liquids or electricity. Burns were sustained at the workplace and outdoors. Flame accidents in males were the leading cause of death with overall mortality of 8.2%. 13.9% of admissions needed intensive care and average length of hospital stay was 32.6 days. The annual number of patients undergoing burn related surgery has continuously increased reflecting a more aggressive surgical management. Our ongoing efforts are to promote prevention program and look for changes in the incidence of burn injury based on these epidemiologic features. Further study for implications of changes in management protocols and policies on treatment outcomes would improve the provision of appropriate care for the patients.

The limited immunomodulatory effects of escharectomy on the kinetics of endotoxin, cytokines, and adhesion molecules in major burns.

Escharectomy has been shown to improve the survival rates and the outcomes in burns. This observational study was conducted to assess the role of escharectomy on the inflammatory mediators in major burns. Seventeen ASA physical status II or status III adult surviving major burn patients were recruited. When the escharectomy was scheduled, a series of blood samples was obtained at -3 and -1 days preoperation, and +1 and +3 postoperation. The changing levels of endotoxin, cytokines, and adhesion molecules were measured with a quantitative sandwich immunoassay. Extensive escharectomy did not appear to have any significant impact on the levels of tumor necrosis factor alpha, interleukin-10, soluble intracellular adhesion molecule-1 and soluble vascular adhesion molecule-1. Meanwhile, endotoxin and E-selectin were significantly decreased after escharectomy. Escharectomy appeared to have a limited immunomodulatory effect on the inflammatory mediators in systemic inflammatory responses induced by major burns. This is probably related to the timing and extent of surgery, and the complex nature of burn-related inflammation.

Fluoxetine inhibits A-type potassium currents in primary cultured rat hippocampal neurons.

The effects of fluoxetine (Prozac) on the transient A-currents (IA) in primary cultured hippocampal neurons were examined using the whole-cell patch clamp technique. Fluoxetine did not significantly decrease the peak amplitude of whole-cell K+ currents, but it accelerated the decay rate of inactivation, and thus decreased the current amplitude at the end of the pulse. For further analysis, IA and delayed rectifier K+ currents (IDR) were isolated from total K+ currents. Fluoxetine decreased IA (the integral of the outward current) in a concentration-dependent manner with an IC50 of 5.54 microM. Norfluoxetine, the major active metabolite of fluoxetine, was a more potent inhibitor of IA than was fluoxetine, with an IC50 of 0.90 microM. Fluoxetine (3 microM) inhibited IA in a voltage-dependent manner over the whole range of membrane potentials tested. Analysis of the time dependence of inhibition gave estimates of 34.72 microM(-1) s(-1) and 116.39 s(-1) for the rate constants of association and dissociation, respectively. The resulting apparent Kd was 3.35 microM, similar to the IC50 value obtained from the concentration-response curve. In current clamp configuration, fluoxetine (3 microM) induced depolarization of resting membrane potential and reduced the rate of action potential. Our results indicate that fluoxetine produces a concentration- and voltage-dependent inhibition of IA, and that this effect could affect the excitability of hippocampal neurons.