Luca La Colla

No adjustment vs. adjustment formula as input weight for propofol target-controlled infusion in morbidly obese patients.

Background and objective The purpose of this prospective, randomized, double-blind study was to determine the predictive performance of target-controlled infusions of propofol in morbidly obese patients using the ‘Marsh’ pharmacokinetic parameter set. Methods Twenty-four patients (ASA II or III, age 25–62 years, BMI 35.5–61.7) were randomly allocated to receive propofol target-controlled infusion based on a weight adjustment formula (group adjusted) or without adjustment [group total body weight (TBW)]. Anaesthesia was induced by a propofol-targeted concentration of 6 μg ml−1 that was subsequently adapted to maintain stable bispectral index values ranging between 40 and 50. Arterial blood samples were collected before the start of the infusion and every 15 min thereafter to determine the predictive performances. Results There were no statistically significant differences between the groups with regard to performance errors, divergence and wobble. Results are presented as median (interquartiles). Median performance error and median absolute performance error were −31.7 (−35.9, −19.4) and 31.7% (20.2, 35.9) for group adjusted and −16.3 (−26.3, 2.2) and 20.6% (14.8, 26.9) for group TBW, respectively. Wobble median value was 7.4% (3.8, 8.4) for group adjusted and 8.2% (7.0, 9.6) for group TBW. As for wobble and divergence, no statistically significant differences were found between groups. Conclusion Weight adjustment causes a clinically unacceptable performance bias, which is not corrected when TBW is used as an input to the ‘Marsh’ model. It is, therefore, advisable to administer propofol to morbidly obese patients by titration to targeted processed-EEG values.

Predictive Performance of the ‘Minto’ Remifentanil Pharmacokinetic Parameter Set in Morbidly Obese Patients Ensuing from a New Method for Calculating Lean Body Mass

AbstractBackground and Objectives: In a previous article, we showed that the pharmacokinetic set of remifentanil used for target-controlled infusion (TCI) might be biased in obese patients because it incorporates flawed equations for the calculation of lean body mass (LBM), which is a covariate of several pharmacokinetic parameters in this set. The objectives of this study were to determine the predictive performance of the original pharmacokinetic set, which incorporates the James equation for LBM calculation, and to determine the predictive performance of the pharmacokinetic set when a new method to calculate LBM was used (the Janmahasatian equations). Methods: This was an observational study with intraoperative observations and no follow-up. Fifteen morbidly obese inpatients scheduled for bariatric surgery were included in the study. The intervention included manually controlled continuous infusion of remifentanil during the surgery and analysis of arterial blood samples to determine the arterial remifentanil concentration, to be compared with concentrations predicted by either the unadjusted or the adjusted pharmacokinetic set. The statistical analysis included parametric and non-parametric tests on continuous variables and determination of the median performance error (MDPE), median absolute performance error (MDAPE), divergence and wobble. Results: The median values (interquartile ranges) of the MDPE, MDAPE, divergence and wobble for the James equations during maintenance were −53.4% (−58.7% to −49.2%), 53.4% (49.0–58.7%), 3.3% (2.9–4.7%) and 1.4% h−1 (1.1–2.5% h−1), respectively. The respective values for the Janmahasatian equations were −18.9% (−24.2% to −10.4%), 20.5% (13.3–24.8%), 2.6% (−0.7% to 4.5%) and 1.9% h−1 (1.4–3.0% h−1). The performance (in terms of the MDPE and MDAPE) of the corrected pharmacokinetic set was better than that of the uncorrected one. Conclusion: The predictive performance of the original pharmacokinetic set is not clinically acceptable. Use of a corrected LBM value in morbidly obese patients corrects this pharmacokinetic set and allows its use in obese patients. The ‘fictitious height’ can be a valid alternative for use of TCI infusion of remifentanil in morbidly obese patients until commercially available infusion pumps and research software are updated and new LBM equations are implemented in their algorithms.

Greater peripheral blood flow but less bleeding with propofol versus sevoflurane during spine surgery: a possible physiologic model?

Study Design. Prospective, randomized, single blind. Objective. To compare the effects of sevoflurane and propofol on lumbar-paraspinal-muscles regional blood flow, as well as bleeding when controlled hypotension is used. Summary of Background Data. Controlled hypotension is the technique of choice to reduce blood loss during spine surgery, but changes in blood flow occurring to lumbar paraspinal muscles during controlled hypotension with propofol and sevoflurane, as well as the entity of bleeding, are unknown. Methods. Blood flow was assessed by means of a laser Doppler flowmeter during the prehypotensive and hypotensive (defined as a 15% reduction of baseline mean arterial pressure) period in 28 patients (aged 28–73 years, American Society of Anesthesiologists (ASA) I–II) undergoing lumbar spine surgery. Patients were randomized to receive either sevoflurane or propofol as main anesthetic agent to achieve hypotension. At the end of the surgery, blood loss was calculated and intraoperative bleeding (Visual Analogue Scale ranging from 0 to 100) was evaluated by the surgeon. Results. Peripheral Blood flow was significantly greater in the propofol group both before and during the hypotensive period (median values of 32.7 FU vs. 7.7 and 38.5 FU vs. 10.5, respectively). Despite this fact, blood loss and intraoperative bleeding were significantly reduced when propofol had been used (P < 0.05). Conclusion. Despite the greater blood flow when it is used, propofol causes less bleeding than sevoflurane during spine surgery and could be more indicated to produce hypotension during anesthesia. Moreover, it is possible to explain our findings hypothesizing a selective vasodilation of propofol (postcapillary, venous vasodilation), different from that of sevoflurane (precapillary, arteriolar vasodilation).

Is an Adductor Canal Block Really Better Than a Femoral Block for Anterior Cruciate Ligament Reconstruction

anesthetics in AC) is only sensory. In these conditions, it is not surprising that a femoral block using an anesthetic rather than analgesic concentration of 0.5% ropivacaine would produce a motor block (femoral but not AC block). 2. AC space is a very small space, which is too small to accommodate a volume of 20 ml. In these conditions what was the rationale for choosing a 20-ml volume versus 10 ml or less?2,3 3. For the past 20 yr, the concentration and volume of local anesthetics used for perioperative analgesia have decreased in order to minimize any motor block when performing a femoral block. Nowadays, the use of 0.2% or even 0.1% ropivacaine and a volume of 10 ml rather than 20 ml is recommended. Therefore, it would have been much more clinically relevant to use 10 ml of 0.1% or 0.2% ropivacaine to assess the relative benefit of each approach.4,5 4. Assessing motor function after a block would be more clinically relevant if done after, rather than before, surgery. 5. Patients undergoing ACL are usually young. Since the duration of a block has been established to vary with age, shorter in young versus older adults,6 under these conditions, it is likely that most patients could have recovered from the block within 12 h.2 Are the effects reported at 24 h a reflection of those observed at 12 h?

A Double-Blind, Randomized, Placebo-Controlled, Two-Dose Comparative Study of Botulinum Toxin Type A for Treating Glabellar Lines in Japanese Subjects: What If Sample Size and Statistical Tests Mattered?

We read with interest the article published by Harii and Kawashima [1]. While the authors are to be commended for investigating the effect of different doses of botulinum toxin type A (BTX-A) in Japanese subjects, there are several issues with both the design of the study and the statistical analysis used. With respect to the study design, despite the statement from the authors that it was a prospective, randomized, double-blind, placebo-controlled study, it does not appear to be so. There was no hypothesis to test; it appears to be a pilot study. Even if the authors wanted to test the hypothesis that halving the dose of BTXA (from 20 to 10 U) would not result in a significant decrease in a patient’s response rate, the sample size calculation is still missing. In fact, in order for a particular finding to be claimed as significant (or not), the study must have enough power. The authors do not state anything about the expected change in response rate values and therefore it is almost impossible to perform a prestudy sample size calculation. However, it is possible to perform a post-hoc sample size calculation or power analysis on the statistical tests they have used from their data. In particular, considering a rough response rate of 90% in the 20-U group, a 10% clinically significant difference in response rate, and the Bonferroni’s correction for multiple comparisons, more than 160 patients per group would have been required (considering the ‘‘standard’’ a error of 0.05 and a power of 0.8). Moreover, the randomization method is not clearly explained. Another critical point is the statistical analysis. The authors state that the t test and ANOVA were used for continuous variables. This may not be the correct way to go. Are all the variables normally distributed? If not, nonparametric tests should be used. Moreover, the authors state they used a nonparametric test on categorical variables. Why? Could a categorical variable be non-normally distributed? While this study is interesting for plastic and cosmetic surgeons and dermatologists, appropriate statistical analysis of data from trials is fundamental to draw adequate conclusions. We recommend that all authors perform the right sample size calculation before beginning any type of prospective, randomized, controlled trial and use the correct statistical tests afterward. This is the only way to convince readers that what they claim to be significant is really so. We hope our suggestions will be useful to other authors who will be doing similar studies in the future.

Dipyrone Increases the Blood Flow of Arterial Dorsal Skin Flaps: Are Prospective Studies Always Properly Designed?

We read with interest the article published by Gulmez et al. [1]. While the authors are to be commended for their goal of conducting a prospective, randomized, double-blind trial about the effect of dipyrone on blood flow and necrosis (i.e., flap survival), there are several issues with respect to the design of the study and the statistical analysis used. With respect to study design, the major issue is that there is no reference to any sample size calculation. In fact, in order for a particular finding to be claimed as significant (or not), the study must have enough power. In this particular case, the expected change in blood flow should be stated and from that the sample size should be calculated (e.g., considering the ‘‘standard’’ a error of 0.05 and a power of 0.8). Moreover, there is no reference to the randomization method. Another critical point we want to bring up is the statistical analysis used. The authors state that ‘‘Student’s ttest at a p level of significance less than 0.05 was used to compare the percentage of necrotic area and blood flow changes from baseline for each time point measure.’’ This may not be the correct way to go. Are all the variables normally distributed? If not, nonparametric tests should be used. Moreover, this study involves both tests between groups and tests within the same individuals (i.e., repeated measurements on blood flow and fraction of necrosis). Therefore, close attention should be paid to whether use of a t test for unpaired or paired data is appropriate and, similarly, to the use of either a Wilcoxon rank-sum test or signed-rank test. While this study is extremely interesting for plastic surgeons, appropriate statistical analysis of data from trials is crucial for adequate conclusions. In addition, we have recently shown that the anesthetic technique used affects regional blood flow in spine surgery [2]. Because most patients undergoing plastic surgery procedures are under general anesthesia, it would be interesting to investigate the effect of different anesthetic techniques on flap vascularization and viability. We hope our suggestions will be useful to other authors who will be involved in similar studies in the future.