Tumescent technique for local anesthesia improves safety in large-volume liposuction

The tumescent technique for local anesthesia improves the safety of large-volume liposuction ( > or = 1500 ml of fat) by virtually eliminating surgical blood loss and by completely eliminating the risks of general anesthesia. Results of two prospective studies of large-volume liposuction using the tumescent technique are reported. In 112 patients, the mean lidocaine dosage was 33.3 mg/kg, the mean volume of aspirated material was 2657 ml, and the mean volume of supernatant fat was 1945 ml. The mean volume of whole blood aspirated by liposuction was 18.5 ml. For each 1000 ml of fat removed, 9.7 ml of whole blood was suctioned. In 31 large-volume liposuction patients treated in 1991, the mean difference between preoperative and 1-week postoperative hematocrits was -1.9 percent. The last 87 patients received no parenteral sedation. In a second study, a 75-kg woman received 35 mg/kg of lidocaine on two separate occasions, first without liposuction and 25 days later with liposuction; peak plasma lidocaine concentrations occurred at 14 and 11 hours after beginning the infiltration and were 2.37 and 1.86 micrograms/ml, respectively.     

A prospective study of Clostridium difficile infection and colonization in pediatric oncology patients

BACKGROUND: Tumescent liposuction has proven to be an extremely safe and effective method of liposuction. However, the infusion of tumescent anesthesia can take 1 hour or more to complete. OBJECTIVE: To document the types, dosages, and routes of administration of premedication utilized by four experienced tumescent liposuction surgeons. To determine if infusion rates for tumescent anesthesia are affected by types of premedication. METHODS: Four experienced liposuction surgeons were asked to review their most recent 100 tumescent liposuction patients with respect to types and dosages of premedication and routes of administration. Data were also provided on corresponding infusion pump settings and infusion rates. Volumes of tumescent anesthesia and corresponding volumes of fat aspirated were also collected on the same 400 patients. RESULTS: Infusion of tumescent anesthesia could be performed more rapidly in patients who were given greater amounts of premedication. Volumes of tumescent anesthesia infused were generally two or more times the volume of fat aspirated. Patients could be infused with less premedication if slow infiltration was employed. CONCLUSION: Infusion rates for tumescent anesthesia can be increased of greater amounts of premedication are given. However, this must be balanced against the safety of the premedication.     

Use of preoperative subcutaneous "wetting solution" and epidural block anesthesia for liposuction in the office-based surgical suite

Uniform saturation of subcutaneous fat using the "wetting solution" formula described by Klein for his "tumescent technique" has been shown to decrease operative blood loss associated with liposuction procedures and to eliminate the requirement for general anesthesia for selected patients. However, we found this infusate provided an inadequate level of anesthesia for many of our patients. We use preoperative infusion of Klein's epinephrine and lidocaine containing wetting solution in our lipoplasty practice only for control of blood loss and postoperative pain. Our anesthetic of choice for liposuction is the epidural block technique, which provides consistent intraoperative comfort for the patient. We report our experience with 85 consecutive lipoplasty patients who underwent liposuction under epidural anesthesia after subcutaneous fat perfusion with Klein's wetting solution. Our epidural block technique uses the rapidly metabolized local anesthetic agent, chloroprocaine, which has the lowest systemic toxicity risk of any local anesthetic agent. Chloroprocaine's anesthetic characteristics are particularly well suited for the outpatient surgery patient with few undesirable side effects.     

Should interstitial thermometry be used for deep hyperthermia?

This study was performed to determine whether premedication with midazolam and fentanyl prevents reliable detection of an i.v. lidocaine test dose. Thirty ASA physical status I or II patients received either 3 mL of saline or 1.5 mg of midazolam (1.5 mL) plus 75 microg of fentanyl (1.5 mL) i.v. in a randomized, double-blind fashion. Five minutes later, lidocaine 1 mg/kg was injected i.v. At 1.5 min before and every minute after lidocaine administration, each subject was questioned regarding the presence of four symptoms of systemic lidocaine toxicity. Any new tinnitus, perioral numbness, metallic taste, or light-headedness within 5 min after lidocaine administration was considered a positive response. All 15 patients in the saline group (100% sensitivity) had a positive response to i.v. lidocaine, but only 9 of 15 patients in the sedation group had a positive response (60% sensitivity; P = 0.017). We conclude that midazolam and fentanyl premedication decreases the reliability of subjective detection of i.v. lidocaine. Implications: Anesthesiologists often rely on subjective symptoms to prevent local anesthetic toxicity while performing regional anesthesia. Sedatives are often administered during the administration of regional anesthesia. This study demonstrates that typical sedation decreases the reliability of detection of local anesthetic toxicity by subjective symptoms.     

Plasma concentrations and cardiovascular influence of lidocaine infusions during isoflurane anesthesia in healthy dogs and dogs with subaortic stenosis

OBJECTIVE: To determine the plasma concentrations and cardiovascular changes that occur in healthy dogs and dogs with aortic stenosis that are given an infusion of lidocaine during isoflurane anesthesia. STUDY DESIGN: Phase 1, controlled randomized cross-over trial; Phase 2, before and after trial ANIMALS: Phase 1, 6 healthy dogs (4 female, 2 male) weighing 23.8 +/- 7.4 kg; Phase 2, 7 dogs (4 female, 3 male) with moderate to severe subaortic stenosis (confirmed by Doppler echocardiography) weighing 31.1 +/- 14.5 kg. METHODS: After mask induction, intubation, and institution of positive pressure ventilation, instrumentation was performed to measure hemodynamic variables. After baseline, measurement at an end-tidal isoflurane concentration of 1.9% (phase 1) or 1.85% (phase 2), a loading dose infusion of lidocaine at 400 microg/kg/min was given. Phase 1: Maintenance doses of lidocaine were administered consecutively (40, 120, and 200 microg/kg/min) after the loading dose (given for 10, 10, and 5 minutes, respectively) in advance of each maintenance concentrations. Measurements were taken at the end of each loading dose and at 25 and 35 minutes during each maintenance level. The same animals on a different day were given dextrose 5% and acted as the control. Phase 2: Dogs were studied on a single occasion during an infusion of lidocaine at 120 microg/kg/ min given after the loading dose (10 minutes). Measurements occurred after the loading dose and at 25 and 35 minutes. A blood sample for lidocaine concentration was taken at 70 minutes. Data were compared using a one-way ANOVA for phase 1, and between phase 1 and 2. Statistical analysis for phase 2 was performed using a paired t-test with a Bonferroni correction. A P value < or = .05 was considered significant. RESULTS: Phase 1: Plasma lidocaine concentrations achieved with 40, 120, and 200 microg of lidocaine/kg/min were 2.70, 5.27, and 7.17 microg/mL, respectively. A significant increase in heart rate (HR) (all concentrations), central venous pressure (CVP), mean pulmonary arterial pressure (PAP), and a decrease in stroke index (SI) (200 microg/kg/min) were observed. An increase in systemic vascular resistance (SVR) and mean PAP, and a decrease in SI also followed the loading dose given before the 200 microg/kg/min infusion. No other significant differences from the control measurements, during dextrose 5% infusion alone, were detected. Phase 2: Plasma lidocaine concentrations achieved were 5.35, 4.23, 4.23, and 5.60 microg/mL at 10, 25, 35, and 70 minutes, respectively. They were not significantly different from concentrations found in our healthy dogs at the same infusions. A significant but small increase in CVP compared with baseline was noted after the loading dose. There were no significant differences from baseline shown in all other cardiovascular data. There were no statistically significant differences in any measurements taken during the lidocaine infusion between the dogs in phase 1 and phase 2. Dogs with aortic stenosis tended to have a lower cardiac index than healthy dogs at baseline (88 v 121 mL/kg/min) and during lidocaine infusion (81 v 111 mL/kg/min). A small, statistically significant difference in systolic PAP was present at baseline. CONCLUSIONS: There does not appear to be any detrimental cardiovascular effects related to an infusion of lidocaine at 120 microg/kg/min during isoflurane anesthesia in healthy dogs or dogs with aortic stenosis. The technique used in this study resulted in therapeutic plasma concentrations of lidocaine.CLINICAL RELEVANCE: Methods shown in the study can be used in clinical cases to achieve therapeutic lidocaine levels without significant cardiovascular depression during isoflurane anesthesia.     

Subarachnoid anesthesia with minimal doses of lidocaine in ambulatory arthroscopic surgery of the knee

The objective is demonstrate that subarachnoid anesthesia with 2% isobaric lidocaine at low doses (0.5 mg/kg) is safe and effective for outpatient arthroscopic surgery of the knee. This was a prospective study of 150 ASA I-III patients undergoing arthroscopic knee surgery as outpatients under subarachnoid anesthesia. With no prior vascular filling, we provided blockade by administering 2% isobaric lidocaine at a dose of 0.5 mg/kg through a Sprotte 25G needle without vasoconstrictor. We assessed effectiveness and degree of sensory-motor blockade, cardiovascular repercussions, recovery time (until reversal of blockade, ambulation, micturition and discharge) as well as side effects observed. The mean dose of lidocaine used was 33.44 +/- 4.16 mg. The sensory-motor blockade achieved provided optimum conditions for prevention of ischemia and the practice of the surgical procedure in all cases. Surgery lasted a mean 38 +/- 10 min. Hemodynamic changes were not clinically significant and no patients additional fluids, atropine or vasopressors. Time from start of blockade until ambulation, micturition and discharge from the recovery unit were 123 +/- 8.3, 175 +/- 12.4 and 194 +/- 13.4 min, respectively. Micturition was spontaneous in all cases. Complications recorded were cephalea and backache. In conclusion, subarachnoid anesthesia at low doses of 2% isobaric lidocaine provides excellent conditions for practicing arthroscopic surgery of the knee on outpatients, with minimum side effects.     

Safety considerations and fluid resuscitation in liposuction: an analysis of 53 consecutive patients

There is no agreement as to appropriate fluid resuscitation in patients undergoing liposuction. This has assumed greater significance, as surgeons have undertaken larger volume aspirations (> or = 4 liters) and the potential complications of hypovolemia and fluid overload have materialized. This prospective study of 53 consecutive healthy patients undergoing liposuction using a superwet technique served to develop general guidelines for safe perioperative fluid management, especially in regard to large-volume aspirations. In this context, "aspirate" is defined as the total fat and fluid that is removed during liposuction. All patients were monitored using standard noninvasive hemodynamic monitoring. Thirty-six patients were monitored perioperatively with Foley catheters. The 53 patients underwent liposuction alone. We did not include patients who underwent concurrent aesthetic surgical procedures because our intention was to establish fluid administration guidelines for the liposuction patient. There were no significant complications in our series. The intraoperative fluid ratio, defined as (intravenous fluid + infiltrate)/aspirate, was 2.1 for the small-volume group and 1.4 for the large-volume group. These values were significantly different (p < .001, t test). Average urine output in the operating room and recovery room and on the floor was satisfactory (> 0.5 to 1 cc/kg/hr) and did not relate to volume aspirated (p = 0.21, 0.91, and 0.6, respectively, t test). Four patients who underwent "large-volume" aspirations (> or = 4 liters) had transient hypotension, which was immediately responsive to crystalloid fluid boluses in the first postoperative hours. All other patients required only maintenance intravenous crystalloid postoperatively until oral intake had been resumed. There were no statistically significant differences in postoperative fluid administration between the small- and large-volume groups. Ninety-three percent of patients were discharged within 24 hours of surgery. Our suggested guidelines for fluid resuscitation based on this retrospective study are as follows: (1) small volume (< 4 liters aspirated): maintenance fluid + subcutaneous wetting solution; (2) large volume (> or = 4 liters aspirated): maintenance fluid + subcutaneous wetting solution + 0.25 cc of intravenous crystalloid per cc of aspirate removed after 4 liters. This formula has since been used in the care of 94 patients who have undergone liposuction exclusively. All patients have had unremarkable hospital courses. These guidelines do not replace sound clinical judgment. Good communication between the surgeon and anesthesiologist is critical to optimal patient care and safety.     

Modest release of adipsin/factor D by liposuction when using the superwet or tumescent technique

Human adipsin is recognized to be identical to factor D, which plays an important role in activation of the alternative complement pathway. Since adipsin/factor D is present in high amounts in adipose tissue, liposuction theoretically could result in an increased release of this serine protease into the bloodstream. In the present study, adipsin/factor D was measured in 22 patients undergoing syringe-assisted liposuction using the superwet or tumescent technique. Despite a relatively high mean aspirate volume (2648 ml), only a very modest increase in adipsin/factor D concentration was found during liposuction. All values before, during, and after liposuction were within the range found in healthy blood donors. Furthermore, there was no correlation between adipsin/factor D values and C3 activation products. We conclude that liposuction with the present techniques results in a very modest release of adipsin/factor D that is not associated with increased complement activation.     

A Phase I dose escalation trial of continuous infusion paclitaxel to augment high dose cyclophosphamide and thiotepa plus stem cell rescue for the treatment of patients with advanced breast carcinoma

BACKGROUND: Paclitaxel, an effective chemotherapeutic agent in the management of breast carcinoma, may have activity in women whose disease has recurred after high dose chemotherapy. With this is mind the authors explored the addition of a 120-hour continuous infusion of paclitaxel to a previously reported regimen comprised of high dose cyclophosphamide and thiotepa. METHODS: Thirty-one women with advanced breast carcinoma (30 patients with Stage IV disease and 1 patient with Stage IIIB disease) underwent harvest and cryopreservation of bone marrow and/or peripheral blood progenitor cells. High dose cyclophosphamide (2.5 g/m2) and thiotepa (225 mg/m2) were administered intravenously on Days -7, -5, and -3. Paclitaxel was administered as a 120-hour continuous infusion starting on Day -7. RESULTS: Three patients were treated at the initial cohort dose of 50 mg/m2 (over 120 hours), 6 patients at 100 mg/m2, 6 patients at 125 mg/m2, 6 patients at 150 mg/m2, 6 patients at 180 mg/m2, and 4 patients at 210 mg/m2. All patients completed the treatment protocol as planned with no associated transplant-related deaths. Mucositis as evidenced by either stomatitis or noninfectious diarrhea was experienced by all patients and was determined to be the dose-limiting toxicity at the 210 mg/m2 dose level. One patient with dose-limiting mucositis required intubation for airway protection and also experienced Grade 3 (according to the Cancer and Leukemia Group B common toxicity grading scale) pulmonary and neurologic toxicity. Only one Grade 3 toxicity was encountered below the maximum tolerated dose in a patient who developed diffuse alveolar hemorrhage at a dose of 125 mg/m2. No allergic reactions or clinical evidence of peripheral neuropathies were encountered. Cardiac, hepatic, and renal toxicities were minimal. Response rates in this previously treated patient population were difficult to assess in light of the high incidence of bone metastases; an overall response rate of 24% was obtained. CONCLUSIONS: Paclitaxel at a dose of 180 mg/m2 as a 120-hour continuous infusion may be added safely to high dose cyclophosphamide and thiotepa with autologous stem cell rescue. Further studies are ongoing to evaluate the efficacy and further define the toxicity of this recommended Phase II dose.     

A comparative interaction of epinephrine with enflurane, isoflurane, and halothane in man

Forty-eight patients undergoing transphenoidal removal of pituitary tumors received submucosal injections of epinephrine in saline solution during halothane, enflurane, or isoflurane anesthesia. Twelve additional patients received epinephrine in 0.5 percent lidocaine while anesthetized with halothane. Positive evidence of ventricular irritability was given by the appearance of 3 or more premature ventricular contractions during or following injection. Positive or negative responses were plotted against the total dose of epinephrine in mug/kg body weight. From these data, the dose producing a positive response in 50 percent of patients (ED50) was calculated. An ED50 of 2.1 mug/kg for halothane, 3.7 mug/kg for halothane-lidocaine, 10.9 mug/kg for enflurane, and 6.7 mug/kg for isoflurane indicates the relative safety of these agents when epinephrine is injected for hemostasis. The data also suggest that lidocaine given with the epinephrine protects against ventricular arrhythmias.     

The antibacterial effects of tumescent liposuction fluid

Tumescent liposuction is currently one of the most commonly performed aesthetic procedures. Despite the variable use of preoperative antibiotics, infection is uncommon. Prior works suggest that the low incidence of infection may be due to lidocaine's antibacterial properties. However, these properties have only been demonstrated using concentrations of lidocaine above 0.8%, significantly higher than those used in tumescent liposuction. The purpose of this study was to determine if the commonly used tumescent fluid containing 0.1% lidocaine, 1:1000,000 epinephrine, and 0.012 mEq sodium bicarbonate possesses antibacterial activity. Using the broth microdilution method, the minimum inhibitory concentrations of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Group A beta-hemolytic Streptococcus were determined after exposure to either lidocaine, epinephrine, bicarbonate, or the combination of all three agents. To determine if there were significant growth differences not detectable by the broth microdilution method, bacterial concentrations were obtained through the use of a spectrophotometer, and significant differences from the controls were calculated by one-way analysis of variance. To determine if prolonged exposure to the tumescent mix would alter bacterial growth, a Killing Time study was also undertaken. The results indicated that the minimum inhibitory concentration of lidocaine was not less than 0.5% for any of the bacteria, whereas the lowest minimum inhibitory concentration of the combined solution was 0.25%. The lowest inhibitory concentration as determined by spectrophotometric analysis for the combined solution was 0.13% (p < 0.01). Analysis of the Killing Time data revealed no inhibition of bacterial growth over time. In conclusion, lidocaine, epinephrine, and bicarbonate do exhibit antibacterial properties at high concentrations. However, the commonly used tumescent mixture containing dilute concentrations of these agents does not significantly inhibit the growth of commonly encountered bacteria.     

Superantigen-based immunotherapy: a phase I trial of PNU-214565, a monoclonal antibody-staphylococcal enterotoxin A recombinant fusion protein, in advanced pancreatic and colorectal cancer

PURPOSE: To establish the maximum-tolerated dose (MTD) and define the toxicities of a single-dose infusion of PNU-214565, a recombinant Escherichia coli-derived fusion protein of Staphylococcal enterotoxin A (SEA) and the Fab-fragment of the C242 monoclonal antibody in patients with advanced colorectal and pancreatic carcinomas. To investigate the capability of PNU-214565 to induce a superantigen (SAg) response resulting in cytokine production and tumor regression. PATIENTS AND METHODS: Twenty-one patients (age range, 39 to 76 years; median, 64; 12 men, nine women; 18 colorectal, three pancreatic cancers) were treated with a single 3-hour infusion of PNU-214565, with doses ranging from 0.01 to 1.5 ng/kg. All patients had prior chemotherapy and a good performance status Eastern Cooperative Oncology Group [ECOG] performance status [PS] = 0 [n = 10]; PS = 1 [n = 11]), 10 had prior radiation, and 18 had prior surgery. RESULTS: Fever and hypotension were the most common toxicities. Fever of any grade occurred in 16 of 21 patients (76%): four of 21 (19%) with grade 2 and two of 21 (9.5%) with grade 3. Hypotension of any grade occurred in 13 of 21 (62%): four of 21 with grade 2 and one of 21 (5%) with grade 3. Interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF alpha) induction correlated with toxicity. In the two patients with grade 3 fever, peak IL-2 and TNF alpha levels were 2.9 IU/mL and 165 pg/mL, and 8.3 IU/mL and 245 pg/mL, respectively. Transient, > or = 50% decreases in circulating monocytes were observed in 17 of 21 patients as early as 0.5 hours (median time, 2 hours) from the start of infusion. Decreases (mean 33%) in circulating lymphocytes were observed in seven of 21 patients. All three patients with grade 3 toxicity were treated at the 0.5-ng/kg dose. The significance of baseline anti-SEA, human antimouse antibody (HAMA), CA242-soluble antigen levels, and T-cell receptor variable beta region (TCR V beta) subsets and histocompatibility leukocyte antigen-DR (HLA-DR) genotypes was assessed as possible predictors of toxicity. All toxicities were transient and easily managed. No grade 3 toxicity occurred at the higher dose levels. CONCLUSION: PNU-214565, a SAg-based tumor targeted therapy, is safe when given as a single 3-hour infusion at doses up to 1.5 ng/kg. The MTD for a single dose was not determined. The safety of a repeated dose schedule is currently under investigation, beginning with doses determined to be safe in this trial.     

Effects of epidural and systemic lidocaine on sympathetic activity and mesenteric circulation in rabbits

BACKGROUND: The mechanisms producing hemodynamic changes during epidural anesthesia are incompletely understood. This study examines the sympathetic block and splanchnic venodilatation that result from extensive thoracolumbar epidural anesthesia in rabbits using direct measurements of sympathetic efferent nerve activity (SENA) and mesenteric vein diameter (VD). METHODS: Epidural catheters were inserted in rabbits anesthetized with alpha-chloralose, paralyzed with vecuronium, and receiving mechanical ventilation. Arterial pressure was monitored with a femoral cannula, heart rate was determined from the pressure signal, SENA was measured from a postganglionic splanchnic nerve, and VD was measured from segments of ileum externalized in situ. Epidural anesthesia was induced with 0.4 ml/kg lidocaine, using concentrations of either 0.5, 1, or 1.5%. Control animals received intramuscular lidocaine in a dose of either 6 or 15 mg/kg. After recovery from epidural anesthesia, complete sympathetic blockade was induced by systemic administration of the ganglionic blocker hexamethonium (HX). Individual groups included from five to eight animals. RESULTS: A mild decrease in arterial pressure and SENA followed the larger dose of intramuscular lidocaine, but no changes occurred in VD in the control animals exposed to systemic lidocaine at levels comparable to that in the epidural groups (0.96-3.58 micrograms/ml). Epidural injectate extended from T2 to L5. All concentrations of epidural lidocaine produced comparable degrees of hypotension (-53.5 to -61.4%), decreased SENA (-82.6 to -95.5%), and increased VD (7.5 to 10.2%). The duration of the changes was greater with more concentrated lidocaine. Hexamethonium produced changes in arterial pressure and VD comparable to those evoked by epidural anesthesia. CONCLUSIONS: Epidural anesthesia increases splanchnic venous capacitance by markedly decreasing splanchnic sympathetic nerve activity.     

Phase I safety and pharmacokinetics study of micronized atovaquone in human immunodeficiency virus-infected infants and children. Pediatric AIDS Clinical Trials Group

A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 micrograms/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 micrograms/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day.     

Experience with once daily dosing of gentamicin: considerations regarding dosing and monitoring

Plasma concentrations of gentamicin following a fixed dose of 240 mg once daily to patients with normal renal function were measured. The purpose was to establish guidelines to achieve a sufficiently high peak concentration with an appropriately low risk of accumulation. In 40 patients, 1-hour concentrations of plasma gentamicin had a median of 9.3 mg/l (range: 4.5-19.0 mg/l) and 9.7 mg/l (range: 3.6-14.6 mg/l) on days 1 and 3 of gentamicin treatment, respectively. Thirty-nine patients had 1-hour concentrations > 5 mg/l. The 1-hour concentrations varied considerably intra- and interindividually but showed a significant inverse correlation with body weight, surface area and the estimated endogenous creatinine clearance. The plasma gentamicin elimination half-life correlated significantly with age and inversely with body weight and creatinine clearance. There was no increase in the mean plasma creatinine from day 0 to day 4. No patients showed signs of nephrotoxicity, although 2 patients, both elderly and with low body weight, showed signs of beginning gentamicin accumulation. In conclusion, gentamicin treatment with the dose of 240 mg once daily in 3 days to adults with normal kidney function generally does not require adjustment or monitoring. However, the dose should be increased in young patients with an excessive body weight, and decreased doses are needed for old and underweight patients. Monitoring of trough plasma gentamicin concentration is not necessary with treatment duration of 3 days or less.     

Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy

OBJECTIVE: To evaluate the pharmacokinetics, safety, and efficacy of sertraline in children (6 to 12 years old) and adolescents (13 to 17 years old). METHOD: Children (n = 29) and adolescents (n = 32) with major depression, obsessive-compulsive disorder (OCD), or both received a single dose of 50 mg of sertraline followed, 1 week later, by 35 days of sertraline treatment as follows: (1) either a starting dose of 25 mg/day titrated to 200 mg/day in 25-mg increments or (2) a starting dose of 50 mg/day titrated to 200 mg/day in 50-mg increments. Sertraline and desmethylsertraline pharmacokinetics were determined approximately weekly, and efficacy measures were assessed before drug administration and at the end of treatment. RESULTS: Mean area under the plasma concentration-time curve (AUC), peak plasma concentration (Cmax), and elimination half-life (t1/2) for sertraline and desmethylsertraline were similar to previously reported adult values. No titration-dependent pharmacokinetic or safety differences were seen. While Cmax and AUC0-24 were greater for children versus adolescents, these differences disappeared after parameters were normalized for body weight. Sertraline was well tolerated in both children and adolescents, with adverse experiences similar to those previously reported by adult patients. Efficacy measurements indicated improvement (p < .001) in depression and OCD symptomatology. CONCLUSIONS: Sertraline can be safely administered to pediatric patients using the currently recommended adult titration schedule.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.     

Multicomponent intravenous and epidural anesthesia in aorto-coronary bypass surgery

The influence of epidural anesthesia (CEA) on clinical manifestations, cortisole and adrenocorticotropic hormone (ACTH) level, central hemodynamic values during aorto-coronary bypass surgery (ACBS) in 56 patients aged 42-68 years with preserved functional capacity of the myocardium was studied. Catheterisation of the epidural space was carried out in the evening before the operation according to the standard method at the level of T4-T5 with the use of disposable epidural set. During the procedure before perfusion 2% solution of lidocaine 3.8 +/- 0.2 mg/kg was introduced in epidural space (taking into account test-dose) as a bolus in 3-4 motions. The dose of local anesthetics for infusion was selected separately for each individual case with due regard for hemodynamic values. During artificial circulation additionally local anesthetic was introduced as a bolus, the dose being 4.7 +/- 0.8 mg/kg. At the end of the operation morphine (0.061 +/- 0.001 mg/kg) was introduced. It was established that combined application of intravenous and epidural anesthesia represents highly effective method of anesthesia in aorto-coronary bypass surgery. According to clinical course data, cortisone and ACTH blood contents and hemodynamic parameters, EA provides adequate anesthesia, promotes stabilization of hemodynamic values and creates functionally more advantageous conditions for the myocardium in patients with CHD during aorto-coronary bypass operation. Anesthesiologic aid with the use of EA promotes reduction of intravenous anesthetics expenditure, earlier waking up of the patients in postoperative period and decrease in duration of postoperative artificial lung ventilation.     

Dynamic imaging of the normal pelvic floor

PURPOSE: To present tolerance and toxicity information on previously untreated high-risk early-stage and advanced-stage primary epithelial ovarian cancer patients treated with adjuvant 3-hour paclitaxel and carboplatin. PATIENTS AND METHODS: Consecutive patients with high-risk early-stage and advanced-stage epithelial ovarian cancer underwent maximal surgical debulking and/or staging. Paclitaxel (175 mg/m2) was infused over 3 hours followed by a 30-minute carboplatin infusion (area under the plasma concentration time curve = 7.0-7.5 mg/mL/min) for a planned six (q 21 day) courses. RESULTS: Twenty-two patients underwent 132 cycles and were evaluable for toxicity. Myelosuppression was dose-limiting. Grade 4 granulocytopenia occurred in 31% of the cycles. Grade 3 and 4 thrombocytopenia was uncommon (5%, 1%) and predictable. Delay in administration was necessary in 10 of 132 (7.6%) cycles (5 of 22 patients). Eight of these 10 delays were 7 days. Seventeen of 22 (77%) patients completed therapy without a delay. Non-hematologic toxicity was mild. A significant individual weight gain of 2.5 kg was noted. Among 19 patients with advanced disease, 16 had a complete clinical remission after six cycles of therapy. Nine patients with stage IIB-IV disease have undergone reassessment procedures (four pathologic complete responses, three microscopic positive, two macroscopic positive). Sixteen of 22 (77%) have no evidence of disease, four have no evidence of disease following a secondary therapy, one is under therapy with salvage chemotherapy, and one is dead of disease. Median follow-up is 14 months (range: 6-30 months). Comparatively, the mean carboplatin dose administered was 440 mg/m2 (95% CI, 428-486 mg/m2). CONCLUSION: Paclitaxel and carboplatin administered in this design are well tolerated, with predictable and acceptable hematologic and nonhematologic toxicity. Dose-limiting toxicity is granulocytopenia with relative platelet sparing. Outpatient administration is safe.